Decarboxylation of α-allyl-substituted acetoacetic esters afforded α-allyl ketones that were reduced with L-selectride [LiBH(s-Bu)3] in alcohols RCH(OH)CH2CH2CH=C(Me)CH2R'. The latter reacted with methyl 4-hydroxy-3-formylbenzoate and methyl orthoformate in the presence of p-toluenesulfonic acid to provide trans-tetrahydropyrano[3,2-с][1]benzopyran. In reaction of the E-isomer of alcohol Me2CHCH(OH) CH2CH2CH=C(Me)CH2CH2Ph with CF3SO3H a stereoselective cyclization occurred with the formation of 2,6-disubstituted tetrahydropyran; Prins reaction with 4-bromobenzaldehyde and salicylaldehyde in the presence of boron trifluoride etherate also proceeded stereoselectively giving a substituted tetrahydropyrano-[3,2-c][1]-benzopyran.

Stereoselective synthesis of tetrahydropyran new derivatives underlain by α-allyl ketones

Stereoselective reduction of the ketone carbonyl group in α-allyl-substituted β-keto esters with sodium tetrahydridoborate in the presence of 2 equiv of MnCl2 quantitatively afforded the corresponding syn-isomeric alcohols. The reduction of the same substrates with L-selectride [LiBH(s-Bu)3] in anhydrous THF was characterized by low chemoselectivity, and anti-isomeric alcohols were formed in about 50% yield. Under analogous conditions, α-allyl ketones smoothly reacted with L-selectride to give syn-isomeric alcohols in quantitative yield. The corresponding anti isomers were synthesized by the Mitsunobu reaction of the syn isomers with formic acid, followed by alkaline hydrolysis.

Stereoselective reduction of the ketone group in α-allyl β-keto esters

Stereoselective synthesis of anti-2-aryl-4-en-1-ols from the corresponding syn isomers was accomplished with 71–83% yields via the Mitsunobu reaction

Synthesis of anti-2-aryl-4-en-1-ols from the corresponding syn isomers

Tri- and tetrasubstituted tetrahydropyranes fused to one and two heterocycles with various functional groups (COOEt, Br, MeC=CH2) were synthesized in stereoselective fashion by reactions of syn- and anti-1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols (R = Bu, PhCH2) with trifluoromethanesulfonic acid, aldehydes in the presence of boron trifluoride–diethyl ether complex (Prins reaction), and salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid. The obtained compounds were brought into Suzuki coupling with thiofen-2-ylboronic acid, hydrolysis, and reduction of the ester group with lithium tetrahydridoaluminate. The resulting carboxylic acid was converted to carboxamide, and the alcohol was oxidized to aldehyde which was converted to oxime. The steric configuration of substituents remained unchanged in all chemical transformations.

Stereoselective synthesis of tri- and tetrasubstituted tetrahydropyrans from syn - and anti -1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols and some chemical transformations of the products

Reactions of syn- and anti-4-(4-bromophenyl)-2-methylnon-1-en-5-ols and 3-(4-bromophenyl)-5- methyl-1-phenylhex-5-en-2-ols with trifluoromethanesulfonic acid and salicylaldehyde derivatives in the presence of Et2O · BF3 (Prins reaction) or with salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid stereoselectively afforded tri- and tetrasubstituted tetrahydrofurans with one or two fused heterocycles and various functional groups (COOEt, Br, MeC=CH2). The reactivity of the synthesized compounds toward thiophen-2-ylboronic acid in the Suzuki reaction was studied, and hydrolysis and reduction (LiAlH4) of the ester group therein gave the corresponding carboxylic acids and alcohols. One of the obtained tetrahydrofuran derivatives was converted into amide, aldehyde, and aldehyde oxime. Stereochemical configuration of substituents was retained in all chemical transformations.

Intramolecular hydroalkoxylation of syn - and anti -1-R-2-arylhex-4-en-1-ols. Efficient stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans

Reactions of arylacetic acids with N-methoxymethanamine afford corresponding Weinreb amides which at alkenylation with methallyl and prenyl bromides in the presence of (Me3Si)2N–Na+ form unsaturated amides ArCHRCONMe(OMe) (R = CH2CMe=CH2, CH2C=CMe2). Amides readily react with BuLi and BnMgCl to give ketones ArCHRCOR' (R' = Bu, Bn). A stereoselective reduction of the latter with LiBH(s-Bu)3 leads to a quantitative formation of syn-isomers of 2-aryl-4-en-1-ols.

Stereoselective synthesis of 2-aryl-4-en-1-ols, promising synthons for the preparation of oxygen heterocycles

New α-allylation reactions were performed of CH-acids with carbonyl groups (β-ketoacetic esters, phenylacetone, β-tetralone, ethyl acetate and its α-substituted derivatives) using as deprotonating reagents depending on the substrate acidity sodium hydride, potassium tert-butilate, and sodium bis(trimethylsilyl)-amide. BrCH2CH=CRR′ (R= R′ = H, Me; R = Me, R′ = CH2Ph, CH2CH2Ph) and BrCH2CH=X (X = cyclohexanylidene, 4-pyranylidene, 4-N-Boc-piperidinylidene) were applied as allylating agents.

V. I. Boev

Papers

Stereoselective synthesis of 2-aryl-4-en-1-ols, promising synthons for the preparation of oxygen heterocycles

New reactions of α-allylation of CH-acids with carbonyl groups