Reduction-induced access to novel functionalized quinoline allylic alcohols via Baylis

Abstract

Quinoline derivatives are valuable scaffolds in medicinal and synthetic organic chemistry. In this work, a series of 3-formyl-2-allyloxyquinolines were synthesized from 2-chloro-3-formylquinolines prepared via the Meth-Cohn protocol, followed by acetal protection and alkoxide substitution. The Baylis-Hillman reaction of these quinolinic aldehydes with methyl acrylate in the presence of DABCO afforded the corresponding β-hydroxy acrylate adducts in good yields. To prevent undesired transformations of the hydroxyl functionality, these adducts were protected as tert-butyldimethylsilyl ethers. However, reduction of the silylated Baylis-Hillman adducts with LiAlH₄ did not furnish the anticipated allylic alcohols. Instead, the reaction proceeded through a competing reduction-elimination pathway, leading to mixtures of unsaturated esters and primary alcohols. The product distribution was influenced by the substitution pattern of the quinoline framework.

Keywords

heterocyclic synthesis quinoline derivatives Baylis-Hillman adducts reduction allylic alcohol precursors

Introduction

Quinoline derivatives constitute an important class of heterocyclic compounds owing to their wide range of pharmacological properties. Members of this family have found extensive applications in medicinal chemistry as antimalarial, anti-inflammatory, anti-asthmatic, antibacterial, and antihypertensive agents.^1–7 For instance, simple compounds such as 2-aminoquinoline have been isolated from a North American mushroom known for its antibacterial and anthelmintic properties.⁸ Additionally, several 2-aminoquinoline analogues have demonstrated antiprotozoal,⁹ antidepressant,^10,11 and antihypertensive¹² activities.

Quinine, a naturally occurring quinoline alkaloid historically used as a frontline antimalarial drug, has progressively been replaced by synthetic analogues such as nivaquine,¹³ plasmoquine,¹⁴ mefloquine,¹⁵ and flavoquine.^16,17 Furthermore, 8-hydroxyquinoline derivatives are of particular importance due to the use of their metal complexes, especially bismuth-based compounds, as agricultural fungicides.¹⁸ Halogenated quinolines have also been employed as intestinal antiseptics and antiparasitic agents,¹⁹ while numerous other quinoline-containing compounds exhibit antibacterial,²⁰ antioxidant,²¹ analgesic,²² antiproliferative,²³ and antitubercular²⁴ activities.

Despite their significant pharmacological and industrial relevance, the development of efficient synthetic methods for quinoline derivatives remains an active area of research. Various synthetic routes have been reported,^25–32 including transformations from anilines,^28,33–35 o-acylanilines and substituted carbonyl derivatives,^29,36–38 aromatic imines and alkynes,^39,40 as well as the well-known Meth-Cohn methodology, in which acetanilides are converted into 2-chloro-3-formylquinolines.⁴¹

On the other hand, the Baylis-Hillman reaction represents a powerful carbon–carbon bond-forming process that has attracted considerable interest in recent years. The reaction between an activated alkene and an aldehyde, typically catalyzed by a tertiary amine such as DABCO, provides an efficient route to densely functionalized olefins. This transformation involves the cooperative interaction of three key components: an activated alkene, an electrophile, and a nucleophilic tertiary amine catalyst.

Nevertheless, one of the main limitations of the Baylis–Hillman reaction lies in its inherently slow reaction rate, often requiring several days depending on the nature of the substrates and catalyst employed. Numerous studies have therefore focused on optimizing reaction conditions to enhance both reaction rate and yield. In addition to DABCO, several tertiary amines such as quinuclidine, 3-hydroxyquinuclidine (3-HQD), 3-quinuclidone, indolizine, DMAP, and DBU have been successfully used as catalysts.^42,43

As part of our ongoing work on the synthesis and reactivity of quinoline derivatives,⁴⁴ the present study aimed to access novel allylic alcohols from silylated Baylis-Hillman adducts through reduction under LiAlH₄ conditions. Unexpectedly, this transformation provided alternative unsaturated esters and primary alcohols instead of the targeted allylic alcohols.

Results and discussion

First, 2-chloro-3-formylquinolines 1a-e were prepared according to the procedure described by Meth-Cohn et al.⁴¹ (Table 1). Substitution of chlorine at the 2-position of the quinoline requires prior protection in order to avoid undesired side reactions. This protection step was achieved by refluxing 2-chloro-3-formylquinolines 1a–e with trimethyl orthoformate in methanol, in the presence of a catalytic amount of ammonium nitrate, for 2–3 h. The expected acetals 2a-e were obtained in quantitative yields (Scheme 1).

Table 1.

Synthesis of 2-chloro-3-formylquinoline derivatives 1a-e via the Meth-Cohn protocol.

Product	R¹	R²	R³	M.p. (° C)	Yield (%)
1a	H	H	H	148	65
1b	H	H	Me	137	54
1c	Me	H	H	125	64
1d	H	OMe	H	147	62
1e	Me	Me	H	156	66

Substitution of chlorine with allyl alkoxide was carried out in two steps. First, the alkoxide was generated by reacting sodium hydride in DMF at 0 °C. Subsequently, a solution of quinolinic acetal was added to the freshly prepared alkoxide. The reaction mixture was stirred overnight at 0 °C (Scheme 1), affording ethers 3a-e in excellent yields (Table 2).

Table 2.

Synthesis of acetal intermediates 2a-e and corresponding allyloxy derivatives 3a-e.

Product	M.p. (°C)	Yield (%)	Product	Yield (%)
2a	60	97	3a	94
2b	84	98	3b	52
2c	57	95	3c	95
2d	79	84	3d	77
2e	82	79	3e	60

The next step involved regeneration of the aldehyde function in order to obtain the key intermediates required for the Baylis-Hillman reaction. This was accomplished through acetal hydrolysis using a mixture of THF and distilled water under reflux for 1 h in the presence of p-toluenesulfonic acid as catalyst. The desired quinoline aldehyde ethers 4a-e were obtained in excellent yields (Table 3).

Table 3.

Synthesis of 2-allyloxy-3-formylquinoline derivatives 4a-e.

Product	R¹	R²	R³	M.p. (°C)	Yield (%)
4a	H	H	H	65	96
4b	H	H	Me	86	83
4c	Me	H	H	84	90
4d	H	OMe	H	95	98
4e	Me	Me	H	94	75

As previously mentioned, the main objective was to prepare Baylis-Hillman quinoline adducts for two reasons. First, only a limited number of studies have reported Baylis-Hillman reactions involving quinoline carboxaldehydes, such as the work of E. Srihari et al.⁴⁵ describing the condensation of methyl acrylate with quinoline formyl derivatives. Second, these reactions provide access to allylic alcohols derived from Baylis-Hillman adducts, which are suitable precursors for the preparation of chiral epoxides via the Sharpless epoxidation method.

The reaction of 3-formylquinolines 4a-e with methyl acrylate was carried out at room temperature, with the acrylate acting both as reagent and solvent, in the presence of a catalytic amount of DABCO. The addition of silica to the reaction medium significantly accelerated the condensations. Most reactions were completed within 7 to 11 days depending on the nature and position of substituents on the quinoline ring, affording the corresponding products 5a-e in good yields (Table 4).

Table 4.

Synthesis of Baylis-Hillman adducts 5a-e.

Product	R¹	R²	R³	M.p. (°C)	Yield (%)
5a	H	H	H	Oil	81
5b	H	H	Me	44	77
5c	Me	H	H	77	83
5d	H	OMe	H	Oil	84
5e	Me	Me	H	89	87

However, it was observed that reduction of 5a with LiAlH₄ did not lead to the expected allylic alcohol 9a. Instead, alcohol 8a was obtained as shown in Scheme 2.

To prevent possible side processes during LiAlH₄ reduction, the alcohol function of the Baylis-Hillman adducts 5a-e was protected. The protecting group selected was tert-butyldimethylsilyl ether, known for its stability under both acidic and basic conditions and for its steric bulk, which limits nucleophilic interactions at oxygen. Protection of alcohols 5a-e using tert-butyldimethylsilyl chloride in the presence of 2.5 equivalents of imidazole afforded the corresponding silyl ethers 6a-e in excellent yields (Scheme 3, Table 5).

Table 5.

Synthesis of tert-butyldimethylsilyl-protected Baylis-Hillman adducts 6a-e.

Product	R¹	R²	R³	Yield (%)
6a	H	H	H	70
6b	H	H	Me	58
6c	Me	H	H	88
6d	H	H	OMe	92
6e	Me	Me	H	82

At this stage, the objective was to obtain the corresponding allylic alcohols in order to proceed with a Sharpless epoxidation and thus access chiral epoxides that have not previously been reported for this class of quinoline derivatives. However, the reduction step did not proceed as initially expected. Treatment of the silylated Baylis-Hillman adducts 6a-e with LiAlH₄ in anhydrous diethyl ether did not lead to the desired allylic alcohols, but instead afforded a mixture of two products: the unsaturated esters 7a-e and the primary alcohols 8a-e (Scheme 4).

The E/Z configurations of compounds 7a-e and 8a-e were assigned on the basis of ¹H NMR coupling patterns. In all cases, the major products exhibited spectral features consistent with an E-alkene configuration. The reduction of silylated ethers 6a-e generally led to mixtures of esters and alcohols exclusively displaying the E configuration. However, in the specific case of compound 6a, an additional minor product was detected alongside 7a and 8a. Analysis of its ¹H NMR spectrum allowed its identification as alcohol 8a, bearing a Z-configured double bond (Scheme 5). Although the isomeric alcohols (E)-8a and (Z)-8a could not be separated by column chromatography, their structures were unambiguously assigned based on detailed ¹³C NMR analysis of the mixture.

On the other hand, reduction of compound 6b resulted in a single product in which the ester was fully reduced, affording alcohol 8b. The obtained results are summarized in Table 6.

Table 6.

Synthesis of unsaturated esters 7a-e and corresponding primary alcohols 8a-e.

Product	M.p (°C)	Yield (%)
7a	78	10
7b	-	0
7c	45	33
7d	62	40
7e	74	66
8a	44	90
8b	Oil	86
8c	57	67
8d	45	60
8e	110	34

A plausible mechanism for the formation of compounds 7 and 8 is proposed in Scheme 6. Initially, LiAlH₄ promotes hydride addition to the activated C = C bond of the silylated Baylis-Hillman adduct 6, generating an intermediate that subsequently undergoes β-elimination of the silyl protecting group (OSiMe₂t-Bu), leading to the formation of compounds 7. The predominant E-configuration is consistent with a preferential anti-elimination pathway that furnishes the thermodynamically more stable alkene geometry. In the presence of excess LiAlH₄, the ester group is subsequently reduced through the classical two-step mechanism involving formation of a transient aldehyde intermediate followed by a second hydride transfer to give the corresponding primary alcohols 8 after hydrolytic work-up.

Conclusion

In summary, Meth-Cohn's method remains an efficient approach for the synthesis of functionalized quinolines from their corresponding aniline precursors. Protection of the aldehyde functionality proved essential to enable substitution of the chlorine atom by an alkoxide. The Baylis-Hillman reaction, involving the condensation of methyl acrylate with the activated aldehyde in the presence of DABCO, proceeded smoothly and provided the desired adducts in good yields. Subsequent protection of the β-hydroxy ester moiety using tert-butyldimethylsilyl chloride was necessary to allow further transformations, despite introducing an additional synthetic step. However, reduction of the resulting silylated intermediates with LiAlH₄ did not furnish the expected allylic alcohols. Instead, the reaction led to the formation of unsaturated esters and primary alcohols through a sequential reduction-elimination pathway. This outcome highlights the intrinsic reactivity of these intermediates under strongly reducing conditions.

From a synthetic perspective, the obtained alcohols constitute valuable intermediates. Their oxidation to the corresponding aldehydes, followed by Wittig or Horner–Wadsworth–Emmons olefination, would allow access to diversely substituted quinolinic dienes. These compounds could subsequently undergo intramolecular cycloaddition reactions to generate tetracyclic frameworks, for which the investigation of diastereoselectivity would be of particular interest.

Experimental part

Synthesis of 2-chloro-3-formyl-quinolines

2-Chloro-3-formylquinoline derivatives 1a-e have been synthesized according to the literature procedure.⁴¹

Synthesis of 2-chloro-3-dimethoxymethylquinoline derivatives 2a-e

Compounds 2a-e have been prepared according to the procedure described in our previous work as below.⁴⁴

General method

In a 50 ml flask equipped with an ascending condenser, 1 equivalent of 2-chloro-3-formylquinolines and 2 equivalents of methyl orthoformate dissolved in 3 ml of anhydrous CH₃OH were introduced. The reaction mixture was refluxed for 2 h. After cooling, 2 ml of a 5% solution of Na₂CO₃ were added in order to neutralize the medium. The mixture was extracted with ethyl acetate and washed twice with distilled water; the combined organic phases are dried over anhydrous Na₂SO₄. The solvents were distilled under vacuum and the crude product obtained is purified by column chromatography on silica gel using a mixture of ethyl acetate / petroleum ether (5/95) as eluent.

2-Chloro-3-dimethoxymethylquinoline 2a

White crystals. Yield = 97%. M.p. = 60 °C (Lit. 61 °C).⁴⁴ R_f = 0.15 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.42 (t, 1H, J = 0.9 Hz, H-C₄), 8.03 (ddt, 1H, J = 8.5, 1.1, 0.7 Hz, H-C₈), 7.88 (ddt, 1H, J = 8.1, 1.4, 0.6 Hz, H-C₅), 7.76 (ddd, 1H, J = 8.5, 7.0, 1.5 Hz, H-C₇), 7.59 (ddd, 1H, J = 8.2, 7.0, 1.2 Hz, H-C₆), 5.73 (d, 1H, J = 0.7 Hz, CH(OCH₃)₂), 3.45 (s, 6H, CH(OCH₃)₂). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 149.35 (C_q, C₂), 147.48 (C_q, C_4a), 137.27 (CH, C₄), 133.89 (C_q, C₇), 129.25 (C_q, C_8a), 128.25 (CH, C₈), 128.08 (CH, C₅), 127.25 (CH, C₆), 126.74 (C_q, C₃), 100.40 (CH(OCH₃)₂), 53.90 (2C, CH(OCH₃)₂). HRMS : Calcd for C₁₂H₁₂ClNO₂ [M⁺] : 237.05511, found : 237.0545.

2-Chloro-3-dimethoxymethyl-8-methylquinoline 2b

Yellow crystals. Yield = 98%. M.p. = 84 °C. R_f = 0.29 (eluent: PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.68 (broad s, 1H, H-C₄), 7.79 (d, 1H, J = 8.1 Hz, H-C₅), 7.71 (ddq, 1H, J = 7.2, 1.5, 0.9 Hz, H-C₇), 7.52 (dd, 1H, J = 8.1, 7.2 Hz, H-C₆), 5.70 (d, 1H, J = 0.6 Hz, CH(OCH₃)₂), 3.43 (s, 6H, CH(OCH₃)₂), 2.78 (broad s, 3H, C₈-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 148.88 (C_q, C₂), 148.47 (C_q, C_8a), 140.41 (CH, C₄), 136.99 (C_q, C₈), 133.66 (CH, C₇), 127.83 (CH, C₆), 127.56 (CH, C₅). 126.56 (C_q, C_4a), 126.05 (C_q, C₃), 100.51 (CH(OCH₃)₂), 53.88 (2C, CH(OCH₃)₂), 17.81 (C₈-CH₃). HRMS: Calcd for C₁₃H₁₄ClNO₂ [M⁺] : 251.07076, found : 251.0714.

2-Chloro-3-dimethoxymethyl-6-methylquinoline 2c

White crystals. Yield = 95%. M.p. = 57 °C (Lit. 64 °C).⁴⁴ R_f = 0.17 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.32 (t, 1H, J = 1.0 Hz, H-C₄), 7.91 (d, 1H, J = 8.6 Hz, H-C₈), 7.62–7.60 (m, 1H, H-C₅), 7.56 (dd, 1H, J = 8.6, 2.0 Hz, H-C₇), 5.70 (d, 1H, J = 0.6 Hz, CH(OCH₃)₂)), 3.43 (broad s, 6H, CH(OCH₃)₂), 2.52 (s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 148.4 (C_q, C₂), 146.1 (C_q, C_8a), 137.3 (C_q, C₅), 136.6 (CH, C₄), 133.1 (CH, C₇), 129.1 (C_q, C₆), 127.9 (CH, C₈), 126.9 (CH, C₅), 126.8 (C_q, C_4a), 100.5 (CH(OCH₃)₂), 53.9 (2C, CH(OCH₃)₂), 21.6 (C₆-CH₃). HRMS : Calcd for C₁₃H₁₄ClNO₂ [M⁺] : 251.07076, found : 251.0714.

2-Chloro-3-dimethoxymethyl-7-methoxyquinoline 2d

White crystals. Yield = 84%. M.p. = 79 °C. R_f = 0.22 (eluent: PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.32 (dd, 1H, J = 1.0, 1.0 Hz, H-C₄), 7.73 (d, 1H, J = 8.9 Hz, H-C₅), 7.35 (d, 1H, J = 2.5 Hz, H-C₈), 7.21 (dd, 1H, J = 8.9, 2.5 Hz, H-C₆), 5.70 (d, 1H, J = 0.5 Hz, CH(OCH₃)₂), 3.94 (s, 3H, C₇-OCH₃), 3.43 (s, 6H, CH(OCH₃)₂). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 161.9 (C_q, C₇), 149.7 (C_q, C₂), 149.4 (C_q, C_8a), 136.9 (CH, C₄), 129.0 (CH, C₈), 126.8 (C_q, C₃), 121.2 (C_q, C_4a), 120.5 (CH, C₆), 106.4 (CH, C₅), 100.5 (CH(OCH₃)₂), 55.6 (C₇-OCH₃). 53.9 (2C, CH(OCH₃)₂). HRMS: Calcd for C₁₃H₁₄ClNO₃ [M⁺] : 267.06567, found : 267.0656.

2-Chloro-3-dimethoxymethyl-6,7-dimethylquinoline 2e

White cristals. Yield = 79%. M.p. = 82 °C. R_f = 0.17 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.28 (t, 1H, J = 1.0 Hz, H-C₄), 7.77 (broad s, 1H, H-C₈), 7.60–7.57 (m, 1H, H-C₅), 5.70 (d, 1H, J = 0.6 Hz, CH(OCH₃)₂)), 3.43 (s, 6H, CH(OCH₃)₂), 2.46 (s, 3H, CH₃), 2.43 (s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 148.4 (C_q, C₂), 146.7 (C_q, C_8a), 141.5 (C_q, C₇), 137.3 (C_q, C₆), 136.2 (CH, C₄), 133.1 (CH, C₇), 128.2 (C_q, C₃), 127.6 (CH, C₈), 127.2 (C_q, C₅), 125.4 (C_q, C_4a), 100.6 (CH(OCH₃)₂), 53.9 (2C, CH(OCH₃)₂), 20.6 (CH₃), 20.1 (CH₃).

Synthesis of 2-allyloxy-3-dimethoxymethylquinolines 3a-e

Compounds 3a-e have been prepared according to the procedure described in our previous work as below.⁴⁴

General method

In a 50 ml flask equipped with a refluxing condenser connected to an oil valve, a magnetic bar and a septum was introduced 502 mg (20.93 mmol, 5.6 equiv) of 60% NaH in mineral oil (sodium hydride was washed 3 times with anhydrous n-heptane, the mineral oil dissolved in the solvent was removed using a pipette, while obtaining a fine powder which was subsequently dried by passing a stream of argon) followed by 4 mL of anhydrous DMF under magnetic stirring and argon at 0 °C. A solution of 356 μl (5.24 mmol, 1.4 equiv) of allyl alcohol in 4 mL of anhydrous DMF was introduced, the reaction mixture is allowed to react to form the alkoxide). A solution of 1 g (3.74 mmol in the case of 2d and 2e) of substituted quinolinic acetal 2a-f in 4 mL of anhydrous DMF was added dropwise. The reaction was left stirring under an argon stream overnight.

Distilled water is added and the mixture is extracted with ethyl acetate and the solution are combined and dried over anhydrous Na₂SO₄. The solvents are distilled under vacuum by rotary evaporator, the crude product is chromatographed on a column of silica gel using PE / AcOEt 95:5 as eluent.

2-Allyloxy-3-dimethoxymethylquinoline 3a

Colorless oil. Yield = 94%. R_f = 0.59 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.42 (t, 1 H, J = 0.9 Hz, H-C₄), 7.82 (dtt, 1H, J = 8.4, 0.6, 0.7 Hz, H-C₈), 7.75 (dd, 1H, J = 8.0, 1.5 Hz, H-C₅), 7.61 (ddd, 1H, J = 8.4, 6.9, 1.5 Hz, H-C₇), 7.37 (ddd, 1H, J = 8.0, 6.9, 1.2 Hz, H-C₆), 6.17 (ddt, 1H, J = 17.2, 10.5, 5.3 Hz, CH = CH₂), 5.71 (d, 1H, J = 0.6 Hz, CH(OCH₃)₂), 5.46 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂, H _trans ), 5.27 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.07 (dt, 2H, J = 5.3, 1.5 Hz, OCH₂), 3.42 (s, 6H, CH(OCH₃)₂). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 159.0 (C_q, C₂), 146.3 (C_q, C_8a), 136.3 (C_q, C₄), 133.5 (HC=), 129.7 (CH, C₇), 128.0 (CH, C₈), 126.9 (CH, C₆), 124.8 (C_q, C_4a), 124.2 (CH, C₅), 121.8 (CH, C₃), 117.2 (=CH₂), 99.0 (CH(OCH₃)₂), 66.6 (OCH₂), 53.7 (2C, CH(OCH₃)₂). HRMS : Calcd for C₁₅H₁₇NO₃ [M⁺] : 259.12029, found : 259.1208.

2-Allyloxy-3-dimethoxymethyl-8-methylquinoline 3b

Colorless oil. Yield = 52%. R_f = 0.57 (eluant : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.16 (s, 1H, H-C₄), 7.73 (d, 1H, J = 8.6 Hz, H-C₅), 7.54 (broad s, 1H, H-C₇), 7.47 (dd, 1H, J = 8.4, 1.8 Hz, H-C₆), 6.18 (ddt, 1H, J = 17.2, 10.5, 5.2 Hz, CH = CH₂), 5.72 (broad s, 1H, CH(OCH₃)₂), 5.47 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.28 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.05 (dt, 2H, J = 5.3, 1.5 Hz, OCH₂), 3.42 (s, 6H, CH(OCH₃)₂), 2.49 (s, 3H, C₈-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 148.0 (C_q, C₂), 147.8 (C_q, C_8a), 140.0 (C_q, C₄), 137.0 (C_q, C₈), 133.7 (CH, C₇), 133.4 (HC=), 127.8 (CH, C₆), 127.6 (CH, C₅). 126.0 (C_q, C_4a), 125.9 (C_q, C₃), 117.0 (=CH₂), 100.5 (CH(OCH₃)₂), 66.0 (OCH₂), 54.2 (2C, CH(OCH₃)₂), 16.9 (C₈-CH₃). HRMS : Calcd for C₁₆H₁₉NO₃ [M⁺] : 273.13594, found : 273.1265.

2-Allyloxy-3-dimethoxymethyl-6-methylquinoline 3c

Yellow oil. Yield = 95%. R_f = 0.47 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.14 (t, 1H, J = 1.0 Hz, H-C₄), 7.71 (d, 1H, J = 8.5 Hz, H-C₈), 7.53–7.50 (m, 1H, H-C₅), 7.44 (ddd, 1H, J = 8.5 Hz, 1.5 Hz, 0.5 Hz, H-C₇), 6.16 (ddt, 1H, J = 17.2, 10.5, 5.2 Hz, CH = CH₂), 5.69 (d, 1H, J = 0.7 Hz, CH(OCH₃)₂)), 5.45 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.25 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.05 (dt, 2H, J = 5.3, 1.5 Hz, OCH₂), 3.43 (s, 6H, CH(OCH₃)₂), 2.48 (s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 158.6 (C_q, C₂), 144.6 (C_q, C_8a), 135.8 (C_q, C₄), 133.8 (C_q, C₆), 133.7 (HC=), 131.8 (C_q, C₇), 127.1 (CH, C₅), 126.6 (CH, C₈), 124.7 (C_q, C_4a), 121.2 (C_q, C₃), 117.1 (=CH₂), 99.0 (CH(OCH₃)₂), 66.5 (OCH₂), 53.7 (2C, CH(OCH₃)₂), 21.3 (C₆-CH₃). HRMS : Calcd for C₁₆H₁₉NO₃ [M⁺] : 273.13594, found : 273.1352.

2-Allyloxy-3-dimethoxymethyl-7-methoxyquinoline 3d

Colorless oil. Yield = 77%. R_f = 0.41 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.25 (s, 1H, H-C₄), 7.72 (d, 1H, J = 8.9 Hz, H-C₅), 7.24 (d, 1H, J = 2.5 Hz, H-C₈), 7.18 (dd, 1H, J = 8.9, 2.5 Hz, H-C₆), 6.18 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.69 (d, 1H, J = 0.5 Hz, CH(OCH₃)₂), 5.50 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.31 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.07 (dt, 2H, J = 5.3, 1.5 Hz, OCH₂), 3.93 (s, 3H, C₇-OCH₃), 3.42 (s, 6H, CH(OCH₃)₂). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 160.47 (C_q, C₇), 149.21 (C_q, C₂), 147.63 (C_q, C_8a), 135.45 (CH, C₄), 132.77 (HC = CH₂), 129.79 (CH, C₈), 124.80 (C_q, C₃), 121.40 (C_q, C_4a), 117.93 (CH = CH₂), 117.86 (CH, C₆), 106.38 (CH, C₅), 100.47 (CH(OCH₃)₂), 66.88 (OCH₂), 55.68 (C₇-OCH₃). 53.90 (2C, CH(OCH₃)₂). HRMS : Calcd for C₁₆H₁₉NO₄ [M⁺] : 289.13086, found : 289.1312.

2-Allyloxy-3-dimethoxymethyl-6,7-dimethylquinoline 3e

Colorless oil. Yield = 60%. R_f = 0.51 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.11 (t, 1H, J = 1.0 Hz, H-C₄), 7.62–7.52 (m, 1H, H-C₅), 7.50–7.47 (m, 1H, H-C₈), 6.16 (ddt, 1H, J = 17.2, 10.5, 5.3 Hz, CH = CH₂), 5.69 (d, 1H, J = 0.7 Hz, CH(OCH₃)₂), 5.45 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂, H _trans ), 5.25 (dq, 1H, J = 10.5, 1.7 Hz, CH = CH₂, H _cis ), 5.04 (dt, 2H, J = 5.3, 1.6 Hz, OCH₂), 3.41 (s, 6H, CH(OCH₃)₂), 2.42 (s, 3H, CH₃), 2.39 (s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 158.71 (C_q, C₂), 145.16 (C_q, C_8a), 39.85 (C_q, C₇), 135.47 (CH, C₄), 133.71 (CH = CH₂), 133.61 (C_q, C₆), 127.41 (CH, C₈), 126.63 (CH, C₅), 123.17 (C_q, C_4a), 120.72 (C_q, C₃), 116.97 (=CH₂), 99.09 (CH(OCH₃)₂), 66.40 (OCH₂), 53.70 (2C, CH(OCH₃)₂), 20.36 (CH₃), 19.75 (CH₃).

Synthesis of 2-allyloxy-3-formylquinoline derivatives 4a-e

Compounds 4a-e have been prepared according to the procedure described in our previous work as below.⁴⁴

General method

In a 100 ml flask fitted with a refluxing condenser, a bar magnet and a septum, 2.05 g (7.92 mmol) of substituted 2-allyloxyquinolines and 150 mg (0.792 mmol) of PTSA in a mixture of THF/H₂O (60/40). The mixture was refluxed during 2 h. After cooling the solution was extracted with CH₂Cl₂, washed with water and dried with Na₂SO₄. The solvents were removed in vacuo using a rotary evaporator and the resulting crude product was chromatographed on a silica gel column using PE / AcOEt 95:5 as eluent.

2-Allyloxy-3-formylquinoline 4a

Yellow crystals. Yield = 96%. M.p. = 65°C (Lit. 68 °C).⁴⁴ R_f = 0.33 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 10.52 (s, 1H, CHO), 8.61 (t, 1 H, J = 0.5 Hz, H-C₄), 7.87–7.83 (m, 2H, H-C₈ and H-C₅), 7.73 (ddd, 1H, J = 8.5, 6.9, 1.2 Hz, H-C₇), 7.43 (ddd, 1H, J = 8.0, 6.9, 1.2 Hz, H-C₆), 6.20 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.50 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.33 (dq, 1H, J = 10.5, 1.4 Hz, CH = CH₂, H _cis ), 5.13 (dt, 2H, J = 5.3, 1.5 Hz, OCH₂). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 189.3 (CHO), 160.5 (C_q, C₂), 148.9 (C_q, C_8a), 139.9 (C_q, C₄), 132.9 (HC = CH₂), 132.6 (CH, C₇), 129.8 (CH, C₈), 127.3 (CH, C₅), 125.1 (CH, C₆), 124.4 (C_q, C_4a), 120.0 (C_q, C₃), 118.1 (CH = CH₂), 67.1 (OCH₂). HRMS : Calcd for C₁₃H₁₁NO₂ [M ⁺ ^.] : 213.07843, found : 213.0770.

2-Allyloxy-3-formyl-8-methylquinoline 4b

Yellow crystals. Yield = 83%. M.p. = 86°C. R_f = 0.49 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 10.52 (s, 1H, CHO), 8.53 (broad t, 1H, J = 0.6 Hz, H-C₄), 7.75 (dt, 1H, J = 8.6, 0.9 Hz, H-C₅), 7.61 (broad s, 1H, H-C₇), 7.57 (ddd, 1H, J = 8.6, 2.0, 0.6 Hz, H-C₆), 6.20 (ddt, 1H, J = 17.2, 10.5 Hz, 5.2 Hz, CH = CH₂), 5.50 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.33 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.10 (dt, 1H, J = 5.3, 1.5 Hz, OCH₂), 2.50 (s, 3H, C₈-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 189.3 (CHO), 161.0 (C_q, C₂), 148.0 (C_q, C_8a), 136.52 (C_q, C₈), 134.80 (C_q, C₄), 130.80 (C_q, C₇), 130.0 (CH = CH₂), 125.49 (CH, C₅), 124.00 (C_q, C_4a), 123.0 (C_q, C₃), 121.42 (C_q, C₆), 118.05 (CH = CH₂), 66.01 (OCH₂), 18.0 (C₈-CH₃). HRMS : Calcd for C₁₄H₁₃NO₂ [M ⁺ ^.] : 227.09408, found : 227.0955.

2-Allyloxy-3-formyl-6-methylquinoline 4c

Yellow crystals. Yield = 90%. M.p. = 84°C (Lit. 94 °C).⁴⁴ R_f = 0.35 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 10.52 (s, 1H, CHO), 8.53 (broad s, 1H, H-C₄), 7.75 (d, 1H, J = 8.6 Hz, H-C₈), 7.61 (broad s, 1H, H-C₅), 7.56 (dd, 1H, J = 8.5, 2.0 Hz, H-C₇), 6.20 (ddt, 1H, J = 17.2, 10.5, 5.2 Hz, CH = CH₂), 5.49 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.32 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.11 (dt, 1H, J = 5.5, 1.4 Hz, OCH₂), 2.50 (s, 3H, C₈-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 189.40 (CHO), 160.18 (C_q, C₂), 147.32 (C_q, C_8a), 139.29 (C_q, C₄), 134.85 (C_q, C₆), 134.80 (HC = CH₂), 133.05 (CH, C₇), 128.62 (CH, C₅), 126.99 (C_q, C₈), 124.41 (C_q, C_4a), 120.0 (C_q, C₃), 117.93 (CH = CH₂), 66.98 (OCH₂), 21.24 (C₆-CH₃). HRMS : Calcd for C₁₄H₁₃NO₂ [M ⁺ ^.] : 227.09408, found : 227.0955.

2-Allyloxy-3-formyl-7-methoxyquinoline 4d

Yellow crystals. Yield = 98%. M.p. = 95°C. R_f = 0.23 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 10.47 (s, 1H, CHO), 8.61 (broad d, 1H, J = 0.5 Hz, H-C₄), 7.72 (d, 1H, J = 8.9 Hz, H-C₅), 7.19 (broad dd, 1H, J = 2.5, 0.6 Hz, H-C₈), 7.06 (ddd, 1H, J = 8.9, 2.5, 0.6 Hz, H-C₆), 6.20 (ddt, 1H, J = 17.2, 10.5, 5.2 Hz, CH = CH₂), 5.49 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.33 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.11 (dt, 1H, J = 5.5, 1.5 Hz, OCH₂), 3.97 (s, 3H, OCH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 189.05 (CHO), 163.60 (C_q, C₇), 161.35 (C_q, C₂), 151.31 (C_q, C_8a), 139.34 (C_q, C₄), 132.99 (HC = CH₂), 130.94 (C_q, C₈), 119.35 (C_q, C₃), 117.93 (CH = CH₂), 117.70 (C_q, C_4a), 106.27 (CH, C₅), 67.0 (OCH₂), 55.68 (OCH₃). HRMS : Calcd for C₁₄H₁₃NO₃ [M ⁺ ^.] : 243.08899, found : 243.08954.

2-Allyloxy-3-formyl-6,7-dimethylquinoline 4e

Yellow crystals. Yield = 75%. M.p. = 94°C. R_f = 0.38 (eluent : PE / AcOEt 4:1). ¹H NMR (400 MHz, CDCl₃) δ ppm : 10.49 (s, 1H, CHO), 8.49 (broad t, 1H, J = 0.4 Hz, H-C₄), 7.64–7.61 (m, 1H, H-C₈), 7.58–7.54 (m, 1H, H-C₅), 6.19 (ddt, 1H, J = 17.2, 10.5, 5.2 Hz, H-C = C), 5.48 (dq, 1H, J = 17.2, 1.6 Hz, H _trans ), 5.32 (dq, 1H, J = 10.5, 1.5 Hz, H _cis ), 5.09 (dt, 1H, J = 5.5, 1.4 Hz, OCH₂), 2.45 (broad d, 3H, J = 0.4 Hz, CH₃), 2.45 (broad d, 3H, J = 0.4 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 189.41 (CHO), 160.35 (C_q, C₂), 147.90 (C_q, C_8a), 143.60 (C_q, C₇), 138.92 (CH, C₄), 134.38 (C_q, C₆), 133.11 (HC = CH₂), 128.96 (CH, C₅), 126.99 (CH, C₈), 122.91 (C_q, C_4a), 119.19 (C_q, C₃), 117.82 (CH = CH₂), 66.85 (OCH₂), 20.71 (CH₃), 19.70 (CH₃). HRMS : Calcd for C₁₅H₁₅NO₂ [M ⁺ ^.] : 241.10973, found : 241.1122.

Methyl 2-((2-allyloxyquinol-3-yl)(hydroxymethyl)acrylate derivatives 5a-e

General method

Silica gel (350 mg), DABCO (22 mg, 0.2 mmol, ca. 0.15 equiv), methyl acrylate (7 mL, 77 mmol, 58 equiv in the case of 4b or 4c), and substituted or unsubstituted aldehyde (300 mg, 1.32 mmol in the case of 4b or 4c) were introduced into a 25 mL flask. The reaction mixture was left to stand under magnetic stirring at room temperature for 7 to 11 days. When the reaction was complete (monitored by TLC), the crude product was purified by silica gel column chromatography using PE / AcOEt 85:15 as eluent.

Methyl 2-((2-allyloxyquinol-3-yl)(hydroxymethyl))acrylate 5a

Colorless oil. Yield = 81%. R_f = 0.46 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 3433 (O-H), 1724 (C = O), 1623 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.20 (broad d, 1H, J = 0.9 Hz, H-C₄), 7.85 (dd, 1H, J = 8.3, 0.8 Hz, H-C₈), 7.74 (dm, 1H, J = 8.0 Hz, H-C₅), 7.58 (ddd, 1H, J = 8,4, 6.9, 1.5 Hz, H-C₇), 7.40 (ddd, 1H, J = 8.0, 7.0, 1.2 Hz, H-C₆), 6.35 (broad t, 1H, J = 0.8 Hz, C = CH₂), 6.12 (ddt, 1H, J = 17.2, 10.5 Hz, 5.5 Hz, CH = CH₂), 5.90 (m, 1H, CHOH), 5.80 (m, 2H, C = CH₂), 5.40 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.27 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.03 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, OCH₂), 5.02 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, OCH₂), 3.75 (s, 3H, CO₂CH₃), 3.69 (m, 1H, OH). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.94 (CO), 158.68 (C_q, C₂), 145.82 (C_q, C_8a), 140.31 (C_q, C = CH₂), 136.01 (CH, C₄), 133.24 (CH = CH₂), 129.49 (CH, C₇), 127.74 (CH, C₈), 126.91 (CH, C₅), 126.84 (CH, C₆), 125.19 (C_q, C₃), 125.10 (C_q, C_4a), 124.30 (C = CH₂), 117.64 (CH = CH₂), 68.36 (CHOH), 66.72 (OCH₂), 52.09 (CO₂CH₃). HRMS : Calcd for C₁₇H₁₇NO₄ [M⁺] : 299.11521, found : 299.1167.

Methyl 2-((2-allyloxy-8-methylquinol-3-yl)(hydroxymethyl))acrylate 5b

White crystals. Yield = 77%. M.p. = 44°C. R_f = 0.49 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 3430 (O-H), 1729 (C = O), 1624 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.08 (d, 1H, J = 0.8 Hz, H-C₄), 7.59 (dm, 1H, J = 8.0 Hz, H-C₅), 7.46 (ddq, 1H, J = 7.1, 1.5, 0.8 Hz, H-C₇), 7.27 (dd, 1H, J = 8.0, 7.0 Hz, H-C₆), 6,36 (dd, 1H, J = 0.9, 0.6 Hz, C = CH₂), 6.13 (ddt, 1H, J = 17.2, 10.5, 5.6 Hz, CH = CH₂), 5.91 (m, 1H, CHOH), 5.81 (t, 2H, J = 1.1 Hz, C = CH₂), 5.41 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.26 (dq, 1H, J = 10.5, 1.3 Hz, CH = CH₂, H _cis ), 5.05 (dddd, 1H, J = 13.4, 5.6, 1.6, 1.3 Hz, OCH₂), 3,74 (s, 3H, CO₂CH₃), 3.68 (m, 1H, OH), 2.68 (t, 3H, J = 0.8 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.95 (CO), 157.62 (C_q, C₂), 144.59 (C_q, C_8a), 140.40 (C_q, C = CH₂), 136.31 (CH, C₄), 134.96 (CH, C₈), 133.45 (CH = CH₂), 129.65 (CH, C₇), 126.97 (CH, C₅), 126.78 (C = CH₂), 125.55 (CH, C₅), 124.50 (C_q, C₃), 124.50 (C_q, C_4a), 123.94 (CH, C₆), 117.65 (C = CH₂), 68.40 (CHOH), 66.60 (OCH₂), 52.05 (CO₂CH₃), 17.70 (CH₃). HRMS : Calcd for C₁₈H₁₉NO₄ [M⁺] : 313.13086, found : 313.1330.

Methyl 2-((2-allyloxy-6-methylquinol-3-yl)(hydroxymethyl))acrylate 5c

White crystals. Yield = 83%. M.p. = 77°C. R_f = 0.47 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 3413 (O-H), 1726 (C = O), 1624 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.02 (broad t, 1H, J = 1.0 Hz, H-C₄), 7.71 (d, 1H, J = 8.5 Hz, H-C₈), 7.50 (dq, 1H, J = 1.1, 0.9 Hz, H-C₅), 7.43 (broad dd, 1H, J = 8.5, 1.9 Hz, H-C₇), 6.36 (broad t, 1H, J = 0.8 Hz, C = CH₂), 6.10 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.90 (m, 1H, CHOH), 5,81 (t, 2H, J = 1.1 Hz, C = CH₂), 5.39 (dq, 1H, J = 17.2, 1.6 Hz CH = CH₂), 5.25 (dq, 1H, J = 10.5, 1.6 Hz, CH = CH₂), 5.01 (dq, 2H, J = 5.5, 1.6 Hz, OCH₂), 3.74 (s, 3H, CO₂CH₃), 3,69 (m, 1H, OH), 2.47 (broad s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.93 (CO), 158.26 (C_q, C₂), 144.10 (C_q, C_8a), 140.40 (C_q, C = CH₂), 135.53 (CH, C₄), 133.90 (CH, C₆), 133.33 (CH = CH₂), 131.52 (CH, C₇), 126.87 (CH, C₅), 126.79 (C = CH₂), 126.53 (CH, C₈), 125.13 (C_q, C₃), 124.93 (C_q, C_4a), 117.54 (CH, C = CH₂), 68.40 (CHOH), 66.62 (OCH₂), 52,05 (CO₂CH₃), 21.31 (CH₃). HRMS : Calcd for C₁₈H₁₉NO₄ [M⁺] : 313.13086, found : 313.1315.

Methyl 2-((2-allyloxy-7-methoxyquinol-3-yl)(hydroxymethyl))acrylate 5d

Colorless oil. Yield = 84%. R_f = 0.41 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 3449 (O-H), 1719 (C = O), 1624 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.01 (broad t, 1H, J = 0.9 Hz, H-C₄), 7.61 (d, 1H, J = 8.8 Hz, H-C₅), 7.18 (broad d, 1H, J = 2.5 Hz, H-C₈), 7.03 (dd, 1H, J = 8.8, 2.5 Hz, H-C₆), 6.36 (broad t, 1H, J = 0.8 Hz, C = CH₂), 6.11 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.89 (m, 1H, CHOH), 5.82 (t, 1H, J = 1.1 Hz, C = CH₂), 5.40 (dq, 1H, J = 5.5, 1.4 Hz, CH = CH₂), 5.26 (dq, 1H, J = 10.5, 1.4 Hz, CH = CH₂), 5.02 (dq, 2H, J = 5.5, 1.6 Hz, OCH₂), 3.92 (s, 3H, OCH₃), 3.75 (s, 3H, CO₂CH₃), 3.62 (m, 1H, OH). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.97 (CO), 161.02 (C_q, C₇), 159.24 (C_q, C₂), 147.60 (C_q, C_8a), 140.48 (C_q, C = CH₂), 135.82 (CH, C₄), 133.28 (CH = CH₂), 128.76 (CH, C₅), 126.67 (C = CH₂), 122.28 (Cq, C₃), 119.93 (Cq, C_4a), 117.54 (CH = CH₂), 116.51 (CH, C₆), 106.09 (CH, C₈), 68.32 (CHOH), 66.65 (OCH₂), 55.48 (OCH₃), 52.3051 (CO₂CH₃). HRMS : Calcd for C₁₈H₁₉NO₅ [M⁺] : 329.12577, found : 329.1231.

Methyl 2-((2-allyloxy-6,7-dimethylquinol-3-yl)(hydroxymethyl))acrylate 5e

White crystals. Yield = 87%. M.p. = 89°C. R_f = 0.44 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 3429 (O-H), 1718 (C = O), 1614 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.98 (tl, 1H, J = 0.9 Hz, H-C₄), 7.60 (broad s, 1H, H-C₅), 7.48 (broad s, 1H, H-C₈), 6.35 (broad t, 1H, J = 0.7 Hz, C = CH₂), 6.11 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.89 (m, 1H, CHOH), 5.80 (t, 1H, J = 1.1 Hz, C = CH₂), 5.39 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂), 5.25 (dq, 1H, J = 10.5, 1.6 Hz, CH = CH₂), 5.00 (ddt, 2H, J = 5.6, 1.5, 0.6 Hz, OCH₂), 3.74 (s, 3H, CO₂CH₃), 3.80–3.45 (m, 1H, OH), 2.42 (broad s, 3H, CH₃), 2.38 (broad s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.96 (CO), 158.35 (C_q, C₂), 144.65 (C_q, C_8a), 140.49 (C_q, C = CH₂), 139.58 (CH, C₇), 135.24 (CH, C₄), 133.74 (C_q, C₆), 133.40 (CH = CH₂), 127.21 (CH, C₈), 126.66 (C = CH₂), 126.56 (CH, C₅), 123.91 (C_q, C_4a), 123.59 (C_q, C₃), 117.47 (CH = CH₂), 68.47 (CHOH), 66.54 (OCH₂), 52.03 (CO₂CH₃), 20.34 (CH₃), 19.75 (CH₃). HRMS : Calcd for C₁₉H₂₁NO₄ [M⁺] : 327.14651, found : 327.1451.

Synthesis of methyl 2-((2-allyloxyquinol-3-yl) (tert-butyldimethylsilyloxy)methyl)acrylate derivatives 6a-e

General method

To a solution of ester 5 (858 mg in the case of 5b, 2.74 mmol) in anhydrous DMF (2.8 mL), imidazole (467 mg, 6.86 mmol, 2.5 equiv) and t-butyldimethylsilyl chloride (578 mg, 3.83 mmol, 1.4 equiv) were successively added. After 24 h of reaction under argon at 0°C, distilled water was added to the reaction mixture, which was then extracted twice with ethyl acetate. Combined organic phases were washed 3 times with distilled water, dried over anhydrous Na₂SO₄ and the solvents removed under vacuum. The resulting crude product was purified by silica gel column chromatography, using PE / AcOEt 85:15 as eluent.

Methyl 2-((2-allyloxyquinol-3-yl)(tert-butyldimethylsilyloxy)methyl)acrylate 6a

Colorless oil. Yield = 70%. R_f = 0.71 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1719 (C = O), 1625 (C = C). ¹H NMR (500 MHz, CDCl₃) δ ppm : 8.09 (broad s, 1H, H-C₄), 7.81 (broad d, 1H, J = 8.0 Hz, H-C₈), 7.72 (dd, 1H, J = 8.0, 0.8 Hz, H-C₅), 7.57 (ddd, 1H, J = 8.0, 7.0, 1.4 Hz, H-C₇), 7,35 (ddd, 1H, J = 8.0, 7.0, 1.1 Hz, H-C₆), 6,32 (d, 1H, J = 1.2 Hz, H_b-C₁₃), 6.13 (ddt, 1H, J = 17.5, 10.5 Hz, 5.5 Hz, CH = CH₂), 6.08 (broad s, 1H, CHOSi), 5.88 (t, 1H, J = 1.2 Hz, H_a-C₁₃), 5.43 (dq, 1H, J = 17.5 Hz, J = 1.5 Hz, H_a-C₂₂) ; 5.25 (dq, 1H, J = 10.5 Hz, J = 1.5 Hz, H_b-C₂₂), 5.08 (ddt, 1H, J = 13.4, 5.4, 1.5 Hz, H_a-C₂₀), 4.98 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, H_b-C₂₀), 3.69 (s, 3H, OCH₃), 0.91 (s, 9H, t-Bu), 0,11 (s, 3H, Si-CH₃), −0,04 (s, 3H, Si- CH₃). ¹³C NMR (125 MHz, CDCl₃) δ ppm : 166.41 (CO), 158.68 (C_q, C₂), 153.43 (C_q, C = CH₂), 145.82 (C_q, C₉), 136,16 (CH, C₄), 134,96 (C_q, C₈), 133.78 (CH = CH₂), 129.37 (CH, C7), 126,78 (C_q, C₃), 125,66 (C = CH₂), 125,42 (CH, C₅), 125.03 (C_q, C_4a), 123.63 (CH, C₆), 117.21 (CH = CH₂), 66.66 (CHOSi) 66.55 (OCH₂), 51.74 (CO₂CH₃), 25.84 (3C, C(CH₃)₃), 18.19 (C_q, C(CH₃)₃), 17.74 (CH₃-C₈), −4.82 (Si-CH₃), −4.94 (Si-CH₃).

Methyl 2-((2-allyloxy-8-methylquinol-3-yl)(tert-butyldimethylsilyloxy)methyl)acrylate 6b

Colorless oil. Yield = 58%. R_f = 0.76 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1726 (C = O), 1625 (C = C). ¹H NMR (500 MHz, CDCl₃) δ ppm : 8.05 (d, 1H, J = 0.6 Hz, H-C₄), 7.57 (d quintuplet, 1H, J = 7.9, 0.7 Hz, H-C₅), 7.45 (ddq, 1H, J = 7.1, 1.4 Hz, J = 0.9 Hz, H-C₇), 7.26 (dd, 1H, J = 7.9, 7.1 Hz, H-C₆), 6.31 (broad dd, 1H, J = 1.4, 0.4 Hz, C = CH₂), 6.15 (ddt, 1H, J = 17.2, 10.5, 5.6 Hz, CH = CH₂), 6.08 (quintuplet, 1H, J = 0.7 Hz CHOSi), 5.87 (t, 1H, J = 1.3 Hz, C = CH₂), 5.43 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.25 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H _cis ), 5.09 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, OCH₂), 4.99 (ddt, 1H, J = 13.4, 5.6, 1.4 Hz, 1H, OCH₂), 3.69 (s, 3H, CO₂CH₃), 2.68 (broad t, J = 0.8 Hz, 3H, CH₃), 0.90 (s, 9H, t-Bu), 0.11 (s, 3H, Si-CH₃), −0.02 (s, 3H, Si-CH₃). ¹³C NMR (125 MHz, CDCl₃) δ ppm : 166.51 (CO), 157.63 (C_q, C₂), 144.59 (C_q, C_8a), 143.12 (C_q, C = CH₂), 136.16 (CH, C₄), 134.96 (C_q, C₈), 133.78 (CH = CH₂), 129.37 (CH, C₇), 126.78 (C_q, C₃), 125.66 (C = CH₂), 125.42 (CH, C₅), 125.03 (C_q, C_4a), 123.63 (CH, C₆), 117.21 (CH = CH₂), 66.66 (CHOSi), 66.55 (OCH₂), 51.74 (CO₂CH₃), 25.84 (3C, C(CH₃)₃), 18.19 (C_q, C(CH₃)₃), 17.74 (C₈-CH₃), −4.82 (Si-CH₃), −4,94 (Si-CH₃). HRMS : Calcd for C₂₄H₃₃NO₄Si [M ⁺ ^.] : 427.21734, found : 427.2155. Calcd for C₂₀H₂₄NO₄Si [M-tBu^+.] : 370.14691, found : 370.1456.

Methyl 2-((2-allyloxy-6-methylquinol-3-yl)(tert-butyldimethylsilyloxy)methyl)acrylate 6c

Colorless oil. Yield = 88%. R_f = 0.74 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1733 (C = O), 1617 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 8.01 (broad t, 1H, J = 1.0 Hz, H-C₄), 7.71 (broad dt, 1H, J = 8.5, 0.9 Hz, H-C₈), 7.52–7.48 (m, 1H, H-C₅), 7.42 (ddd, 1H, J = 8.5, 2.1, 0.4 Hz, H-C₇), 6.30 (dd, 1H, J = 1.4, 0.4 Hz, C = CH₂), 6.12 (ddt, 1H, J = 17.2, 10.5, 5.6 Hz, CH = CH₂), 6.06 (quintuplet, 1H, J = 0.6 Hz CHOSi), 5.84 (t, 1H, J = 1.3 Hz, C = CH₂), 5.42 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.24 (dq, 1H, J = 10.5, 1.4 Hz, CH = CH₂, H _cis ), 5.05 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, OCH₂), 4.95 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, 1H, OCH₂), 3.69 (s, 3H, CO2CH3), 2.48 (quintuplet, J = 0.5 Hz, 3H, CH₃), 0.90 (s, 9H, t-Bu), 0.10 (s, 3H, Si-CH₃), −0.02 (s, 3H, Si-CH₃), ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.50 (CO), 158.26 (C_q, C₂), 144.10 (C_q, C_8a), 143.14 (C_q, C = CH₂), 135.36 (CH, C₄), 133.64 (CH = CH₂), 133.57 (C_q, C₆), 131.22 (CH, C₇), 127.24 (C_q, C₃), 126.76 (CH, C₅), 126.53 (C_q, C₈), 125.69 (C = CH₂), 125.20 (CH, C_4a), 117.09 (CH = CH₂), 66.69 (CHOSi), 66.57 (OCH₂), 51.74 (CO₂CH₃), 25.84 (3C, C(CH₃)₃), 21.28 (CH₃), 18.19 (C_q, C(CH₃)₃), −4.83 (Si-CH₃), −4,94 (Si-CH₃). HRMS : Calcd for C₂₄H₃₃NO₄Si [M ⁺ ^.] : 427.21734, found : 427.2155. Calcd for C₂₀H₂₄NO₄Si [M-tBu^+.] : 370.14691, found : 370.1456.

Methyl 2-((2-allyloxy)-7-methoxyquinol-3-yl)(tert-butyldimethylsilyloxy)methyl)acrylate 6d

Colorless oil. Yield = 92%. R_f = 0.69 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1726 (C = O), 1624 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.98 (broad t, 1H, J = 0.9 Hz, H-C₄), 7.60 (broad d, 1H, J = 8.8 Hz, H-C₅), 7.18 (broad d, 1H, J = 2.6 Hz, H-C₈), 7.01 (dd, 1H, J = 8.8, 2.6 Hz, H-C₆), 6.31 (dd, 1H, J = 1.5, 0.6 Hz, C = CH₂), 6.14 (ddt, 1H, J = 17.2, 10.5, 5.6 Hz, CH = CH₂), 6.05 (quintuplet, 1H, J = 0.7 Hz, CHOSi), 5.89 (t, 1H, J = 1.4 Hz, C = CH₂), 5.43 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂), 5.26 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂), 5.05 (ddt, 1H, J = 13.4, 5.4, 1.5 Hz, OCH₂), 4.96 (ddt, 1H, J = 13.4, 5.6, 1.5 Hz, 1H, OCH₂), 3.92 (s, 3H, OCH₃), 3.69 (s, 3H, CO₂CH₃), 0.89 (s, 9H, t-Bu), 0.10 (s, 3H, Si-CH₃), −0.03 (s, 3H, Si-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.50 (CO), 160.84 (C_q, C₇), 159.25 (C_q, C₂), 147.56 (C_q, C_8a), 143.16 (C_q, C = CH₂), 135.78 (CH, C₄), 133.60 (CH = CH₂), 128.64 (C_q, C5), 125.50 (C = CH₂), 124.52 (CH, C₃), 120.01 (C_q, C_4a), 117.15 (CH = CH₂), 116.21 (CH, C₆), 106.07 (CH, C₈), 66.62 (CHOSi), 66.60 (OCH₂), 55.46 (OCH₃), 51.72 (CO₂CH₃), 25.83 (3C, C(CH₃)₃), 18.18 (C_q, C(CH₃)₃), −4.82 (Si-CH₃), −4,95 (Si-CH₃). HRMS : Calcd for C₂₄H₃₃NO₅Si [M ^+ .] : 443.21225, found : 443.2144. Calcd for C₂₀H₂₄NO₅Si [M-tBu^+.] : 386.14182, found : 386.1413.

Methyl 2-((2-allyloxy)-6,7-dimethoxyquinol-3-yl)(tert-butyldimethylsilyloxy)methyl)acrylate 6e

Colorless oil. Yield = 82%. R_f = 0.77 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1726 (C = O), 1617 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.97 (broad t, 1H, J = 0.9 Hz, H-C₄), 7.59 (broad s, 1H, H-C₅), 7.46 (broad s, 1H, H-C₈), 6.29 (dd, 1H, J = 1.5, 0.5 Hz, C = CH₂), 6.14 (ddt, 1H, J = 17.2, 10.5, 5.6 Hz, CH = CH₂), 6.05 (quintuplet, 1H, J = 0.7 Hz CHOSi), 5.84 (t, 1H, J = 1.4 Hz, C = CH₂), 5.41 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H _trans ), 5.24 (dq, 1H, J = 10.5, 1.6 Hz, CH = CH₂, H _cis ), 5.04 (ddt, 1H, J = 13.5, 5.4, 1.5 Hz, OCH₂), 4.94 (ddt, 1H, J = 13.5, 5.5, 1.5 Hz, 1H, OCH₂), 3.68 (s, 3H, CO₂CH₃), 2.41 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 0.89 (s, 9H, t-Bu), 0.10 (s, 3H, Si-CH₃), −0.03 (s, 3H, Si-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 166.65 (CO), 158.36 (C_q, C₂), 144.64 (C_q, C_8a), 143.40 (C_q, C = CH₂), 139.23 (CH, C₇), 135.12 (CH, C₄), 133.71 (CH = CH₂), 133.40 (C_q, C₆), 127.11 (CH, C₈), 126.55 (CH, C₅), 126.23 (C_q, C₃), 125.54 (C = CH₂), 123.65 (CH, C_4a), 116.99 (CH = CH₂), 66.68 (CHOSi), 66.48 (OCH₂), 51.72 (CO₂CH₃), 25.84 (3C, C(CH₃)₃), 20.30 (CH₃), 19.71 (CH₃), 18.18 (C_q, C(CH₃)₃), −4.82 (Si-CH₃), −4,95 (Si-CH₃), HRMS : Calcd for C₂₅H₃₅NO₄Si [M ⁺ ^.] : 441.23299, found : 441.2328. Calcd for C₂₁H₂₆NO₄Si [M-tBu^+.] : 384.16256, found : 384.1610.

Reaction of reduction

General method

To a solution of substituted or unsubstituted silyl ether (1.1 g) in of anhydrous Et₂O (12.4 mL) which was cooled to 0°C, of lithium aluminum hydride (188 mg, 4.8–4.9 mmol) was carefully added in small portions. The reaction mixture was left under magnetic stirring and argon gas. The reaction was completed after 2 h, and two spots are formed, indicating that two different products have been obtained. A saturated solution of potassium and sodium tartrate was added with great care at the beginning to destroy the aluminum complexes, and then the resulting mixture was extracted twice with ethyl acetate. Combined organic phases were washed 3 times with distilled water. After drying over anhydrous Na₂SO₄ and removal of solvents, the remaining products were separated by silica gel column chromatography using PE / AcOEt 90:10 as eluent.

Methyl (E)-(3-(2-allyloxyquinol-3-yl)-2-methyl)acrylate 7a

White crystals. Yield = 10%. M.p. = 78°C. R_f = 0.70 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1726 (C = O), 1624 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : Mixture of two products, E and Z, difficult to interpret. ¹³C NMR (100 MHz, CDCl₃) δ ppm : 169.26 (CO), 168.69 (CO), 159.25 (C_q, C₂), 158.80 (C_q, C₂), 146.12 (C_q, C_8a), 145.87 (C_q, C_8a), 138.33 (CH), 137.16 (CH), 133.40 (C_q), 133.33 (C_q), 133.15 (CH), 131.78 (C_q), 130.27 (C_q), 130.01 (CH), 129.90 (CH), 129.47 (CH), 127.69 (CH), 127.49 (CH), 127.02 (CH), 126.90 (CH), 124.96 (C_q), 124.69 (C_q), 124.43 (CH), 124.19 (CH), 121.54 (C_q), 120.78 (C_q), 117.49 (CH₂), 117.36 (CH₂), 66.98 (OCH₂), 66.95 (OCH₂), 65.87 (CH₂), 52.18 (CO₂CH₃), 51.58 (CO₂CH₃), 25.80 (CH₃), 21.42 (CH₃), 15.28 (CH₃), 14.38 (CH₃).

Methyl (E)-(3-(2-allyloxy-6-methylquinolein-3-yl)-2-methyl)acrylate 7c

Beige crystals. Yield = 33%. M.p. = 45°C. R_f = 0.74 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm⁻¹) 1711 (C = O), 1602 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.88 (t, 1H, J = 1.0 Hz, H-C₄), 7.85 (qt, 1H, J = 1.5, 1.0 Hz, CH = C-Me), 7.71 (d, 1H, J = 8.5 Hz, H-C₈), 7.5 (t, 1H, J = 1.2 Hz, H-C₅), 6.46 (dd,1H, J = 8.5 Hz, J = 1.9 Hz, H-C₇), 6,17 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5,45 (dq, 1H, J = 17.2 Hz, J = 1.6 Hz, CH = CH₂), 5,27 (dq, 1H, J = 10.4 Hz, J = 1.5 Hz, CH = CH₂), 5,03 (dt, 2H, J = 5.5 Hz, J = 1.5 Hz, OCH₂), 3,84 (s, 3H, CO₂CH₃), 2,49 (s, 3H, CH₃), 2,13 (d, 3H, J = 1,5 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 168.73 (CO), 158.82 (C_q, C₂), 144.44 (C_q, C_8a), 137.85 (CH, C₄), 134.03 (C_q, C₆), 133.50 (CH = CH₂), 133.34 (CH = C-Me), 132.07 (CH, C₇), 130.04 (C_q, CH = C-Me), 126.80 (CH, C₅), 126.72 (CH-C₈), 124.62 (C_q, C_4a), 120.61 (C_q, C₃), 117.37 (CH = CH₂), 66.87 (OCH₂), 52.16 (CO₂CH₃), 21.29 (C₆-CH₃), 14.36 (CH₃). HRMS : Calcd for C₁₈H₁₉NO₃ [M ⁺ ^.] : 297.13594, found : 297.1380.

Methyl (E)-(3-(2-allyloxy-7-methoxyquinolein-3-yl)-2-methyl)acrylate 7d

White crystals. Yield = 40%. M.p. = 62°C. R_f = 0.67 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 1711 (C = O), 1623 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7,91 (broad t, 1H, J = 0.9 Hz, H-C₄), 7.86 (qd, 1H, J = 1.5 Hz, J = 0.9 Hz, CH = C-Me), 7.61 (d, 1H, J = 8.8 Hz, H-C₅), 7.19 (broad d, 1H, J = 2.5 Hz, H-C₈), 7.04 (dd, 1H, J = 8.8, 2.5 Hz, H-C₆), 6.18 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.45 (dq, 1H, J = 17.2, 1.6 Hz, CH = CH₂, H_trans), 5.28 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H_cis), 5.04 (dt, 2H, J = 5.5, 1.5 Hz, OCH₂), 3.94 (s, 3H, OCH₃), 3.84 (s, 3H, CO₂CH₃), 2.14 (d, 3H, J = 1.5 Hz, CH = C-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 168.85 (CO), 161.51 (C_q, C₇), 159.83 (C_q, C₂), 148.01 (C_q, C_8a), 138.09 (CH, C₄), 133.44 (CH = CH₂), 133.29 (CH = C-Me), 129.30 (C_q, CH = C-Me), 128.80 (CH, C₅), 119.46 (C_q, C_4a), 117.99 (C_q, C₃), 117.41 (CH = CH₂), 116.73 (CH, C₄), 106.27 (CH, C₈), 66.90 (OCH₂), 55.54 (OCH₃), 52.13 (CO₂CH₃), 14.41 (CH = C-CH₃). HRMS : Calcd for C₁₈H₁₉NO₄ [M ^+ .] : 313.13086, found : 313.1300.

Methyl (E)-(3-(2-allyloxy-6,7-dimethylquinolein-3-yl)-2-methyl)acrylate 7e

White crystals. Yield = 66%. M.p. = 74°C. R_f = 0.69 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 1713 (C = O), 1619 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.87 (dd, J = 1.0, 0.8 Hz, H-C₄), 7,86 (broad q, 1H, J = 1.5 Hz, CH = C-Me), 7.60 (broad t, 1H, J = 0.8 Hz, H-C₅), 7.47 (d, 1H, J = 0,7 Hz, H-C₈), 6.17 (ddt, 1H, J = 17.2, 10.5, 5.4 Hz, CH = CH₂), 5.45 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂, H_trans), 5.27 (dq, 1H, J = 10.5, 1.5 Hz, CH = CH₂, H_cis), 5.02 (dt, 2H, J = 5.5, 1.5 Hz, OCH₂), 3.84 (s, 3H, CO₂CH₃), 2.43 (d, 3H, J = 0.9 Hz, CH₃), 2.40 (d, 3H, J = 1.0 Hz, CH₃), 2.13 (d, 3H, J = 1.5 Hz, CH = C-CH₃). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 168.83 (CO), 158.93 (C_q, C₂), 144.99 (C_q, C_8a), 140.31 (Cq, C₇), 137.57 (CH, C₄), 133.90 (C_q, C₆), 133.57 (CH = CH₂), 133.50 (CH = C-Me), 129.61 (C_q, CH = C-Me), 127.17 (CH, C₈), 129.75 (C_q, C₅), 123.10 (C_q, C_4a), 119.66 (C_q, C₃), 117.29 (CH = CH₂), 116.73 (CH, C₄), 66.79 (OCH₂), 52.14 (CO₂CH₃), 20.41 (C₆-CH₃), 19.73 (C₇-CH₃), 14.38 (CH = C-CH₃).

(E)-(3-(2-allyloxyquinol-3-yl)-2-methyl)-2-prop-2-en-1-ol 8a

White crystals. Yield = 90%. M.p. = 44°C. R_f = 0.38 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 3405 (O-H), 1609 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.87 (broad t, 1H, J = 1.0 Hz, H-C₄), 7.81 (ddt, J = 8.4, 1H, 0.9, 0.9 Hz, H-C₈), 7.70 (broad dd, 1H, J = 8.0, 1.4 Hz, H-C₅), 7.58 (ddd, 1H, J = 8.4, 7.0, 1.5 Hz, H-C₇), 7.37 (ddd, 1H, J = 8.0, 7.0, 1.2 Hz, H-C₆), 6.66 (septet, 1H, J = 1.4 Hz, CH = CMe), 6.18 (ddt, 1H, J = 17.2, 10.4, 5.6 Hz, CH = CH₂), 5.44 (ddt, 1H, J = 17.2, 1.7, 1.6 Hz, CH = CH₂), 5,27 (ddt, 1H, J = 10.4, 1.7, 1.3 Hz, CH = CH₂), 5.04 (ddd, 1H, J = 5.5, 1.6, 1.3 Hz, OCH₂), 4.26 (d, 2H, J = 0.9 Hz, CH₂OH), 1.93 (d, 3H, J = 1.4 Hz, CH = CCH₃), 1.90–1.77 (broad s, 2H, OH and H₂O). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 159.61 (C_q, C₂), 145.30 (C_q, C_8a), 140.01 (C_q, CH = CMe), 137.26 (CH, C₄), 133.67 (CH = CH₂), 129.04 (CH, C₇), 127.24 (CH, C₅), 126.86 (CH, C₈), 125.09 (C_q, C_4a), 124.12 (CH, C₆), 122.14 (C_q, C₃), 119.01 (CH = CMe), 117.38 (CH = CH₂), 68.75 (CH₂OH), 66.83 (OCH₂CH=), 15.49 (CH = CCH₃). HRMS : Calcd for C₁₆H₁₇NO₂ [M^+ .] : 255.12538, found : 255.1265.

(E)-(3-(2-allyloxy-8-methylquinol-3-yl)-2-methyl)prop-2-en-1-ol 8b

Colorless oil. Yield = 86%. R_f = 0.46 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 3344 (O-H), 1617 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.85 (d, 1H, J = 0.6 Hz, H-C₄), 7.55 (ddq, 1H, J = 7.9, 0.8, 0.6 Hz, H-C₅); 7.44 (ddq, 1H, J = 7.1 Hz, J = 1,4 Hz, J = 0.9 Hz, H-C₇), 7.26 (dd, 1H, J = 7.9 Hz, J = 7.1 Hz, H-C₆), 6.66 (septuplet, 1H, J = 1.4 Hz, CH = CMe), 6.20 (ddt, 1H, J = 17.2, 10.4, 5.6 Hz, CH = CH₂), 5.45 (ddt, J = 17.2, 1.7, 1.6 Hz, CH = CH₂), 5.26 (ddt, 1H, J = 10.4, 1.7, 1.3 Hz, CH = CH₂), 5,05 (dt, 1H, J = 5.6, 1.4 Hz, OCH₂), 4,26 (d, 2H, J = 0.9 Hz, CH₂OH), 2.69 (broad t, 3H, J = 0.9 Hz, C₈-CH₃), 1.92 (d, 3H, J = 1.4 Hz, CH = CCH₃), 1.87–1.63 (broad s, 2H, OH et H₂O). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 158.52 (C_q, C₂), 144.06 (C_q, C_8a), 139.83 (C_q, CH = CMe), 137.59 (CH, C₄), 135.00 (CH, C₈), 133.89 (CH = CH₂), 129.25 (CH, C₇), 125.08 (CH, C₅), 124.84 (C_q, C_4a), 123,76 (CH, C₆), 121.57 (C_q, C₃), 119.10 (CH = CMe), 117.45 (CH = CH₂), 68.81 (CH₂OH), 66.77 (OCH₂CH=), 17.68 (CH₃-C₈), 15.48 (CH = CCH₃). HRMS : Calcd for C₁₇H₁₉NO₂ [M ^+ .] : 269.14103, found : 269.1428.

(E)-3-(2-allyloxy-6-methylquinol-3-yl)-2-methyl)prop-2-en-1-ol 8c

White crystals. Yield = 67%. M.p. = 57°C. R_f = 0.34 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm-1) 3413 (O-H), 1602 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.79 (broad t, 1H, J = 0.9 Hz, H-C₄), 7.70 (d, 1H, J = 8.5 Hz, H-C₈), 7.47 (quintuplet, 1H, J = 0.9 Hz, H-C₆), 7.41 (dd, 1H, J = 8.5, 2.1 Hz, H-C₇), 6.65 (septuplet, 1H, J = 1.4 Hz, CH = CMe), 6.17 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5,43 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂), 5,26 (dq, 1H, J = 10.4, 1.5 Hz, CH = CH₂), 5.02 (dt, 2H, J = 5.5, 1.5 Hz, OCH₂), 4.25 (d, 2H, J = 1.0 Hz, CH₂OH), 2.48 (t, 3H, J = 0.9 Hz, C₆-CH₃), 1.92 (d, 3H, J = 1.4 Hz, CH = CCH₃), 1.87–1.62 (broad s, 2H, OH and H₂O). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 159.17 (C_q, C₂), 144.06 (C_q, C_8a), 139.83 (C_q, CH = CMe), 137.59 (CH, C₄), 135.00 (CH, C₈), 133.89 (CH = CH₂), 129.25 (CH, C₇), 125.08 (CH, C₅), 124.84 (C_q, C_4a), 123.76 (CH, C₆), 121.57 (C_q, C₃), 119.10 (CH = CMe), 117.45 (CH = CH₂), 68.81 (CH₂OH), 66.77 (OCH₂CH-), 17.68 (C₆-CH₃), 15.48 (CH = CCH₃). HRMS : Calcd for C₁₇H₁₉NO₂ [M ^+ .] : 269.14103, found : 269.1402.

(E)-3-(2-allyloxy-7-methoxyquinol-3-yl)-2-methyl)prop-2-en-1-ol 8d

White crystals. Yield = 60%. M.p. = 45°C. R_f = 0.41 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 3399 (O-H), 1623 (C = C). ¹H NMR (400 MHz, CDCl3) δ ppm : 7.79 (d, 1H, J = 0.8 Hz, H-C₄), 7.57 (d, J = 8.8 Hz, H-C₅), 7.18 (broad d, 1H, J = 2.5 Hz, H-C₈), 7.02 (dd, 1H, J = 8.8, 2.5 Hz, H-C₆), 6.62 (septuplet, 1H, J = 1.3 Hz, CH = CMe), 6.17 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.43 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂), 5.27 (dq, J = 10.4, 1.5 Hz, CH = CH₂), 5.02 (dt, 2H, J = 5.5, 1.5 Hz, OCH₂), 4.25 (d, 2H, J = 0.9 Hz, CH₂OH), 3.93 (s, 3H, OCH₃), 1.92 (d, 3H, J = 1.4 Hz, CH = CCH₃), 1.92–1.67 (broad s, 2H, OH and H₂O). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 160.71 (C_q, C₇), 160.10 (C_q, C₂), 147.01 (C_q, C_8a), 139.18 (C_q, CH = CMe), 137.07 (CH, C₄), 133.70 (CH, CH = CH₂), 128.29 (CH, C₅), 119.81 (Cq, C_4a), 119.40 (Cq, C₃), 119.20 (CH = CMe), 117.31 (CH = CH₂), 116.28 (CH, C₆), 106.21 (CH, C₈), 68.88 (CH₂OH), 66.76 (OCH₂CH=), 55.48 (OCH₃), 15.50 (CH = CCH₃). HRMS : Calcd for C₁₇H₁₉NO₃ [M^+ .] : 285.13594, found : 285.1355.

(E)-3-(2-allyloxy-6,7-dimethoxyquinol-3-yl)-2-methyl)prop-2-en-1-ol 8e

White crystals. Yield = 34%. M.p. = 110°C. R_f = 0.35 (eluent : PE / AcOEt 7:3). IR (KBr, ν cm^-1) 3341 (O-H), 1603 (C = C). ¹H NMR (400 MHz, CDCl₃) δ ppm : 7.77 (broad t, 1H, J = 1.0 Hz, H-C₄), 7.59 (broad s, 1H, H-C₅), 7.44 (broad s, 1H, H-C₈), 6.64 (septuplet, 1H, J = 1.4 Hz, CH = CMe), 6.17 (ddt, 1H, J = 17.2, 10.5, 5.5 Hz, CH = CH₂), 5.43 (dq, 1H, J = 17.2, 1.7 Hz, CH = CH₂), 5.25 (dq, 1H, J = 10.5, 1.6 Hz, CH = CH₂), 5.01 (dt, 2H, J = 5.5, 1.5 Hz, OCH₂), 4.25 (d, 2H, J = 0.9 Hz, CH₂OH), 2.42 (broad s, 3H, C6-CH₃), 2.39 (broad s, 3H, C₇-CH₃), 1.92 (d, 3H, J = 1.4 Hz, CH = CCH₃), 1.69 (broad s, 2H, OH and H₂O). ¹³C NMR (100 MHz, CDCl₃) δ ppm : 159.25 (C_q, C₂), 144.15 (C_q, C_8a), 139.40 (C_q, CH = CMe), 139.10 (C_q, C₇), 136.53 (CH, C₄), 133.83 (CH = CH₂), 133.50 (Cq, C₆), 126.77 (CH, C₈), 126.63 (CH, C₅), 123.47 (Cq, C_4a), 121.01 (Cq, C₃), 119.42 (CH = CMe), 117.19 (CH = CH₂), 68.91 (CH₂OH), 66.66 (OCH₂CH=), 20.31 (C6-CH₃), 19.75 (C7-CH₃), 19.49 (CH = CCH₃). HRMS : Calcd for C₁₈H₂₁NO₂ [M^+ .] : 283.15668, found : 283.1596.

Supplemental Material

sj-docx-1-mgc-10.1177_10241221261442224 - Supplemental material for Reduction-induced access to novel functionalized quinoline allylic alcohols via Baylis–Hillman chemistry

Supplemental material, sj-docx-1-mgc-10.1177_10241221261442224 for Reduction-induced access to novel functionalized quinoline allylic alcohols via Baylis–Hillman chemistry by Yacine Hafad, Mohammed Laabassi, Raouf Boulcina and René Grée in Main Group Chemistry

Footnotes

Acknowledgments

The authors gratefully acknowledge Ministry of Higher Education and Scientific Research (Algeria), for the financial support.

ORCID iDs

Mohammed Laabassi

Raouf Boulcina

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Direction Générale de la Recherche Scientifique et du Développement Technologique, (grant number Not applicable).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental material

Supplemental material for this article is available online.

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Product	M.p (°C)	Yield (%)
7a	78	10
7b	-	0
7c	45	33
7d	62	40
7e	74	66
8a	44	90
8b	Oil	86
8c	57	67
8d	45	60
8e	110	34

Product	M.p (°C)	Yield (%)
7a	78	10
7b	-	0
7c	45	33
7d	62	40
7e	74	66
8a	44	90
8b	Oil	86
8c	57	67
8d	45	60
8e	110	34

Product	M.p (°C)	Yield (%)
7a	78	10
7b	-	0
7c	45	33
7d	62	40
7e	74	66
8a	44	90
8b	Oil	86
8c	57	67
8d	45	60
8e	110	34