Conjugate Addition of Organomagnesium Cuprates to Guvacine Derivatives

Abstract

The synthesis of 4‐substituted piperidine‐3‐carboxylates was achieved by conjugate addition of organomagnesium cuprates to N‐methyl and N‐tert‐butoxycarbonyl guvacine derivatives. Good to excellent yields were obtained with primary Grignard reagents containing alkyl, alkenyl, alkynyl, or masked aldehyde groups in a copper(I)‐trimethylsilylacetylide‐catalysed and chlorotrimethylsilane (TMSCl) mediated procedure.

Preparation and Carbocupration–Silylation of Allyl Propiolates: Vicinal Functionalization To Form Polysubstituted (E)-Vinylic Silanes

“…[8][9][10][11][12] Further acceleration and diastereocontrol of cuprate-enone conjugate additions can be achieved through judicious solvent, temperature, and Lewis acid additive selection including chlorotrimethylsilane (TMSCl) or trimethylsilyl trifluoromethanesulfonate (TMSOTf). 2,13,14 The Jennings group previously reported catalytic carbocupration sequences, whereby stereodefined -trialkylsilyl--alkyl-,-unsaturated ethyl esters were generated in high yields. [15][16][17] Those products were subjected to subsequent transformations including a tandem conjugate addition-diastereoselective protonation sequence, 18 -and halogenations, 19,20 and a stereoselective cascade deconjugation-aldol addition-stabilized Peterson olefination.…”