Chemoselective, Regioselective, and E/Z-Diastereoselective Synthesis of 2-Alkylidenetetrahydrofurans by Sequential Reactions of Ambident Dianions and Monoanions

Abstract

A number of novel beta-ketoesters were prepared by regioselective alkylation reactions of simple beta-ketoester dianions. The cyclization of the dianions of these 1,3-dicarbonyl derivatives with 1-bromo-2-chloroethane afforded a variety of 2-alkylidenetetrahydrofurans with very good regioselectivity and E/Z-diastereoselectivity. These products were deprotonated to give novel ambident carbanions. The alkylation of these carbanions with alkyl halides proceeded with very good regioselectivity and E/Z-diastereoselectivity and allowed a convenient synthesis of a great variety of new 2-alkylidenetetrahydrofurans.

Regioselective Synthesis of Functionalized Furans by Cyclization of 1,3‐Bis‐Silyl Enol Ethers with 1‐Chloro‐2,2‐dimethoxyethane

“…The corresponding reaction of (E)-4i has not been carried out. Treatment of methyl (3-methoxydihydrofuran-2-ylidene)acetate [20] with TFA was not successful and resulted in the formation of complex mixtures rather than furan 5a (Scheme 2). This result and the formation of 5i from (Z)-4i indicate that the presence of a methoxy group at C-4 is mandatory for a clean elimination and formation of a furan.…”

Catalytic (3+2) Palladium‐Aminoallyl Cycloaddition with Conjugated Dienes

“…On the other hand, the ethyl ester group can be reduced by DIBAL to give bicyclic product 20 with an allylic alcohol motif.I n addition, treatment of the adduct with LDAw as shown to deprotonate the CÀHb ond adjacent to the exo olefin and generate an extended enolate 24, [14] which was chemoselectively alkylated with 1-iodohexane to give tetrahydroindole 25 with the double bond migrated inside the heterocycle. On the other hand, the ethyl ester group can be reduced by DIBAL to give bicyclic product 20 with an allylic alcohol motif.I n addition, treatment of the adduct with LDAw as shown to deprotonate the CÀHb ond adjacent to the exo olefin and generate an extended enolate 24, [14] which was chemoselectively alkylated with 1-iodohexane to give tetrahydroindole 25 with the double bond migrated inside the heterocycle.…”

“…However,a minoallyl precursors with ap henyl (14)o rb enzoyl (15)g roup on the nitrogen showed no reactivities for the cycloaddition. Besides the ethyl ester (9a), aminoallyl precursors with alarge range of ester groups, including benzyl (9b), methyl (9c), phenyl (9d), and 9fluorenylmethyl (9e)e sters,c an all give the (3+ +2) cycloaddition products.A romatic sulfonyl groups were found suitable as the protecting group for the cyclic carbamate precursor,s ince their corresponding isocyanates are readily available and pyrrolidine products are generated in good yields (9f and 9g).…”

Synthesis of 4-Alkyl- and 4-(ω-Chloroalkyl)-3-hydroxy-5-alkylidenebuten­olides Based On Cyclizations of 4-Alkyl- and 4-(ω-Chloroalkyl)-1,3-bis(tri­methylsilyloxy)buta-1,3-dienes with Oxalyl Chloride

“…Both experiments stand in sharp contrast to the recent successful application of alkyl or chloroalkyl-substituted dianions in cyclizations with 1-bromo-2-chloroethane to give 3-alkyl-or 3-chloroalkyl-2-alkylidenetetrahydrofurans. 6 The failure of the first cyclization can be explained by decarbonylation of the Weinreb amide. Recently, we reported the use of alkyland chloroalkyl-substituted 1,3-bis-silyl enol ethers for the synthesis of 3-alkyl-and 3-(chloroalkyl)salicylates and 3-alkyl-and 3-(chloroalkyl)furans.…”

“…Ethyl 3-Oxotetradecanoate (2h) 14 Ethyl acetoacetate ( 6,23.5,29.25,29.31,29.40,29.48,29.56,30.5,31.9,43.0,49.3 (CH 2 (9).…”