Edward G. Corley

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%.

A diastereospecific, non-racemic synthesis of a novel β-hydroxy-δ-lactone HMG-CoA reductase inhibitor

Abstract The coupling of acyl anion equivalent 12b with chiral synthon 14 , derived from isoascorbic acid, and a highly stereospecific reduction of the resulting β-hydroxy ketone 3 highlight an efficient synthesis of β-hydroxy-δ-lactone 2 .

Asymmetric synthesis of a potent, aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV inhibitor.

A practical asymmetric synthesis of a novel aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV (DPP-4) inhibitor 1 has been developed. Application of a unique three-component cascade coupling with chiral nitro diester 7, which is easily accessed via a highly enantioselective Michael addition of dimethyl malonate to a nitrostyrene, allows for the assembly of the functionalized piperidinone skeleton in one pot. Through a base-catalyzed, dynamic crystallization-driven process, the cis-piperidionone 16a is epimerized to the desired trans isomer 16b, which is directly crystallized from the crude reaction stream in high yield and purity. Isomerization of the allylamide 16b in the presence of RhCl(3) is achieved without any epimerization of the acid/base labile stereogenic center adjacent to the nitro group on the piperidinone ring, while the undesired enamine intermediate is consumed to <0.5% by utilizing a trace amount of HCl generated from RhCl(3). The amino lactam 4, obtained through hydrogenation and hydrolysis, is isolated as its crystalline pTSA salt from the reaction solution directly, as such intramolecular transamidation has been dramatically suppressed via kinetic control. Finally, a Cu(I) catalyzed coupling-cyclization allows for the formation of the tricyclic structure of the potent DPP-4 inhibitor 1. The synthesis, which is suitable for large scale preparation, is accomplished in 23% overall yield.

Diarryl-a-heteroarylmalonates from Cerium(IV)-promoted Reactions of Dialkyl Malonates with Heterocyclic Compounds

Thiophenes, furans and their benzo analogs undergo facile malonylation in the 2-position on reaction with dialkyl malonate radicals generated with cerium (IV) reagent

Anodic N-dearylation of 2-azetidinones

Abstract N-Methoxyphenyl-2-azetidinones are dearylated under mild conditions via anodic oxidation.

Cyclization of electrochemically generated nitrogen radicals. A novel synthesis of 11-substituted dibenzo[a,d]cycloheptenimines

Abstract A novel and convenient synthesis of 11-substituted dibenzo[a,d]cyclo-heptimines 10 via annelatlon of electrochemically generated aminium radicals derived from substituted 5-hydroxylamino-5-methyl-5H-dibenzo[a,d]cycloheptenes 14 is described. The scope and limitations of the reaction as well as the effects of reactor design, current density and electrode material on the yield of 10 and the carbocation rearrangement by-product 28 are discussed.

Cyclization of electrochemically generated nitrogen radicals. : A novel synthesis of 11-substituted dibenzo[a,d]cycloheptenimine derivatives

Abstract A novel and convenient synthesis of 11-substituted dibenzo[a,d]cyclo-heptimines 10 via annelatlon of electrochemically generated aminium radicals derived from substituted 5-hydroxylamino-5-methyl-5H-dibenzo[a,d]cycloheptenes 14 is described. The scope and limitations of the reaction as well as the effects of reactor design, current density and electrode material on the yield of 10 and the carbocation rearrangement by-product 28 are discussed.