Andrew G. Brewster

Memory of chirality effects in aldol cyclisations of 1-(3-oxobutyryl) derivatives of l-4-oxaproline and l-proline isopropyl esters

Abstract Stereoretentive CC bond formations are features of the aldol cyclisations of the 1-(3-oxobutyryl) derivatives of l -4-oxaproline and l -proline isopropyl esters, consistent with the involvement of axially chiral enolate intermediates.

Regioselective Dieckmann cyclisations leading to enantiopure highly functionalised tetramic acid derivatives

Regioselective Dieckmann cyclisations using an N-acyloxazolidine derived from L-serine give substituted tetramic acids in high yield and enantioselectivity. The products are easily deprotected under mild conditions to give hydroxymethyltetramic acids.

A concise approach to functionalised, homochiral tetramic acids

Abstract Dieckmann cyclisation of homochiral N-acyloxazolidines derived from serine gives good to excellent yields of α,α-disubstituted tetramic acid derivatives.

6- vs 7- Ring selectivity during acetal formation

Abstract Acid-catalysed reaction of triol (1) with 2,2-dimethoxypropane gave both six- and seven-membered cyclic acetals. With 1,1-diethoxyethane the 1,3-dioxane was the sole product.

The asymmetric synthesis and conformational analysis of new C2-symmetric macrocycles derived from head-to-head linked α-amino acids and benzene or pyridine

Abstract The synthesis of several novel 15–18-membered macrocycles containing 1,3-disubstituted benzene or 2,6-disubstituted pyridine in a chiral environment is described. The syntheses used a series of di(Nα-tosyl- l -alanylamido)alkanes, which could be prepared in good yield. The macrocyclisation reaction with 1,3-di(bromomethyl)benzene or 2,6-di(bromomethyl)pyridine was facilitated by the use of caesium carbonate as base, and NMR and molecular modelling were used to study the preferred conformations of the macrocycles.

Convenient synthesis of enantiopure cyclic α-hydroxyalkyl α-amino esters

The preparation of cyclic α-hydroxyalkyl α-amino esters, the ring size of which varies varies from 4 to 7 members, in enantiopure form is readily achieved by intramolecular alkylative cyclisation of oxazolidine precursors.

Synthetic approaches to thiathromboxanes. Part 2. Synthesis of structural isomers of thiathromboxane A2

Structural isomers (15) of monothiathromboxane A2 have been prepared from the half-ester (1). The basic strategy involved introduction of the ‘bottom’ side-chain by Michael addition, lactonisation, removal of ethoxycarbonyl, and conventional introduction of the ‘top’ side-chain. A link with a published dithiathromboxane synthesis is described.

Diastereocontrolled synthesis of hydroxylated lactams

Highly diastereoselective reductions and organometallic additions in bicyclic lactams have been observed, which appear to result either from a stereoelectronic interaction of the pyramidalised nitrogen lone pair or from steric interactions in the bicyclic system. These products can be readily deprotected to give hydroxylated lactams.

Stereoselective intramolecular aldol reactions of (4R)-3-(3-oxobutanoyl)-1,3-thiazolidine-4-carboxylates believed to be directed by ‘self-induced’ axial chirality

Essentially complete retention of configuration accompanies the base-induced aldol reaction of the thiazolidinecarboxylate 6c to give the fused heterocycles 7c and 8c and their retroaldol–acylation reactions to give the bicycle 9c.

Synthetic approaches to the thiathromboxanes. Part 1. Preparation of functionalised dihydrothiopyrans

A hetero-Diels–Alder reaction between diethyl thioxomalonate and derivatives of hexa-3,5-dienoic acid yields 5,6,6-trisubstituted 5,6-dihydro-2H-thiopyrans. The hydrolysis and decarboxylation of these compounds has been investigated. The iodo-lactonisation of these compounds has given a variety of products. Efficient routes have been developed to 4-formyl-3a,7a-dihydro-4H-thiopyrano[4,3-b]furan-2(3H)-one dimethyl acetal and the related malonic ester.