Rearrangement of ammonium ylides produced by intramolecular reaction of catalytically generated metal carbenoids. Part 1. Synthesis of cyclic amines

摘要

Cyclic amines have been prepared in good yield by [2,3]-rearrangement of ammonium ylides produced bynintramolecular reaction of copper carbenoids tethered to allylic amines. Copper() acetylacetonate is the optimumncatalyst for carbenoid/ylide generation from the diazo ketone precursor, and reactions must be performed at elevatedntemperatures in order to obtain reasonable reaction rates and high yields. The reaction has been used to preparenfive- to eight-membered cyclic amines. In cases where the substrate possesses a substituent on the tether connectingnthe diazo group to the allylic amine, tandem ylide formation and rearrangement delivers a high yield of the expectedn2,5-dialkylpyrrolidinone or 2,6-dialkylpiperidinone, but low levels of diastereocontrol are obtained.nTwo new methods have been developed for the synthesis of diazo ketones containing a nucleophilic allylic aminensubstituent. The first method involves conjugate addition of allylic amines to unsaturated diazo ketones and is highnyielding but of limited scope. The alternative general sequence involving nitrogen protection, α-diazo ketonenformation, deprotection and allylation can be used to prepare the substrates required for intramolecular tandemnylide formation and rearrangement.