Andrew S. Thompson

Use of an ephedrine alkoxide to mediate enantioselective addition of an acetylide to a prochiral ketone: asymmetric synthesis of the reverse transcriptase inhibitor L-743,726

Abstract The asymmetric synthesis of L-743,726 was achieved in six steps with an overall yield of 31%. The asymmetry was introduced using a lithiated ephedrine to mediate acetylide addition to a trifluoromethyl ketone with an enantiomeric excess of 96–98%.

Efficient synthesis of carbapenems via the oxalimide cyclization. Manipulation of protecting groups at the oxalimide stage

Abstract An efficient synthesis of the carbepenem nucleus from TBDMS protected acetoxyazetidinone via oxalimide cyclization technology is demonstrated. A key step is desilylation of the oxalimide intermediate. Access to a variety of protecting group schemes is demonstrated.

Rhodium-carbenoid-mediated intermolecular O–H insertion reactions: a dramatic additive effect. Application in the synthesis of an ascomycin derivative

Abstract A catalyst system of Rh 2 (oct) 4 /DIPEA or TMU allows for the rapid construction of α-alkoxyketones from the corresponding α-diazo ketone and alcohol. This methodology was applied to the synthesis of immunoregulant 1 .

A stereoselective synthesis of a key 1β-methylcarbapenem intermediate via a diastereoselective decarboxylation

(3S,4S)-3[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-[(R)-1-carboxyethyl]-2-azetidinone 7a was prepared from (3R,4R)-4-acetoxy-3-[(R)-1-t-butyldimethylsilyloxy)ethyl]-2-azetidinone 3 via a sequence involving coupling with 2,2,5-trimethyl-1,3-dioxan-4,6-dione 4, N-silylation, solvolysis of the methylmeldrums acid moiety and a stereoselective acid catalyzed decarboxylation.

Conversion of a silylated hemiacetal into an α-bromoether using trimethylsilylbromide. Synthesis of platelet activating factor antagonist L-659,989.

Abstract An efficient synthesis of platelet activating factor antagonist L-659,989 has been achieved in ten steps from commercially available 5-iodovanillin. The key transformation converts a silylated hemi-acetal into an α-bromoether followed by a highly stereoselective Grignard coupling.

Stereocomplementary reductions of ring fused enelactams

Abstract Selective reductions of ring fused enelactams to trans - and cis -ring fused lactams is described.

Palladium catalyzed diastereoselective addition of secondary alcohols to acyloxyazetidinones

Abstract Palladium catalyzed addition of lactate esters or phenethyl alcohols to acyloxyazetidinones gives 4-oxy-substituted β-lactams with 6-9:1 diastereoselectivity. The stereochemistry of the major products was established as S*S* by X-ray crystallography.