Nigel S. Simpkins

Asymmetric deprotonation of prochiral ketones using chiral lithium amide bases

Abstract A number of chiral secondary amines have been prepared and used as precursors to the corresponding chiral lithium amide bases. Treatment of either cis -2,6-dimethylcyclohexanone or 4- tert -butylcyclohexanone with a chiral lithium amide, followed by electrophilic quench, gives chiral products in up to 88% enantiomeric excess. The results with 4- tert -butylcyclohexanone are in disagreement with an earlier literature report, giving products of lower enantiomeric excess but higher optical rotation.

Poly-orthophenylenes: Synthesis by suzuki coupling and solid state helical structures

Abstract The preparation of ortho-polyphenylene oligomers, having 3–9 rings, using a rational Suzuki coupling strategy, has been achieved, and a helical structure determined for a number of these products by X-ray crystallography.

Simple synthesis of a C2 symmetric vicinal diamine: Highly diastereoselective Grignard addition to a chiral bis-imine

Abstract The reaction of the enantiomerically pure bis -imine derived from glyoxal and ( R )-α-methylbenzylamine with PhMgCl in diethylether is highly diastereoselective, resulting in the selective formation of the C 2 symmetric vicinal diamine 7 .

Chiral Base-Mediated Asymmetric Synthesis of Tricarbonyl(.eta.6-arene)chromium Complexes

Enantiomerically enriched tricarbonyl(η 6 -arene)chromium complexes can be obtained in up to 84% ee from the reaction of certain monosubstituted complexes with Me 3 SiCl, mediated by a chiral lithium amide base

CONCERNING THE ASYMMETRIC METALLATION OF FERROCENES BY CHIRAL LITHIUM AMIDE BASES

The asymmetric metallation of diphenylphosphinyl ferrocene 5h, to give the silyl substituted product 6h was accomplished in 95% yield and 54% ee using the chiral lithium amide base 2; attempts to extend this reaction to other ferrocenes were unsuccessful.

Diastereoselective enolate chemistry using atropisomeric amide

Abstract The alkylations and aldol reactions of certain atropisomeric amides, derived from ortho-tert-butyl aniline, are highly diastereoselective.

New approaches for the synthesis of erythrinan alkaloids.

A concise asymmetric total synthesis of (+)-erysotramidine is described, using chiral base desymmetrisation of a meso-imide, N-acyliminium addition, retro-Diels-Alder cycloaddition and radical cyclisation as the key steps. A related route, starting from a cyclobutene-fused imide, was explored, and established a novel construction of the Erythrina alkaloid skeleton using a key ring-opening/ring-closing metathesis step. Completion of this synthesis was thwarted by problems with the removal of an unwanted vinylic side-chain. Complementary enantiospecific routes to Erythrina systems were explored, starting from (L)-malic acid. Some unexpected observations were made concerning the diastereocontrol in malic acid-derived N-acyliminium ion cyclisations, where changing the protecting group of the alcohol function from acetate to OTIPS resulted in a dramatic change in diastereocontrol. Products from these reactions could be transformed into known intermediates for natural alkaloids, and into (+)-demethoxyerythratidinone itself, by means of radical cyclisations or intramolecular aldol reactions as the key steps.

A study of the synthesis and racemisation of a chiral lithiated tricarbonyl(η6-anisole)chromium complex

Abstract The non-racemic metallated complex derived from tricarbonyl(η 6 -anisole)chromium 1 , formed using the homochiral lithium amide base 2 , undergoes rapid racemisation by intermolecular proton transfer if the neutral chromium complex is present, this problem being minimised if the deprotonation is conducted in the presence of LiCl.

Enantioselective deprotonation of 8-oxabicyclo[3.2.1]octan-3-one systems using homochiral lithium amide bases

Abstract The asymmetric transformation of oxabicyclic ketones 6 and 7 into non-racemic enol silanes 12 (88% ee) and 10 (85% ee), respectively, was achieved using the homochiral lithium amide base 4. Conversion of 10 into a known key intermediate 15 for C-nucleoside synthesis was possible in a highly efficient two step sequence.

Chiral products via asymmetric deprotonation of 4-tert-butylcyclohexanone using chiral lithium amide bases

Abstract The asymmetric deprotonation of 4- tert -butylcyclohexanone using chiral lithium amide bases gives derived silyl enol ether products in up to 88% ee.