INTRAMOLECULAR N-(ACYLOXY)IMINIUM ION ALKYNE CYCLOADDITIONS - A NEW ROUTE TO BICYCLIC ALPHA-AMINO KETONES

The intramolecular cyclocondensation of 15 cyclic N-(acyloxy)iminium cations containing tethered alkyne and alkene nucleophiles is reported (eqs 5 and 6). This route to heterotricyclic systems was specifically demonstrated with substrates in which the heterodiene moiety was contained in five-, six-, and seven-membered azacyclic rings. The stereochemistry of the cycloadducts (Table IV) was controlled primarily by the size and substitution of the starting azacyclic ring. When the azacyclic ring is monosubstituted, the amount of the trans cycloadduct increases as the size of this spectator ring increases from five to seven. In one case the 2-oxazinone ring of an alkyne cycloadduct was subsequently cleaved by ozone to provide a bicyclic a-amino ketone product (eq 21). This result demonstrates that a simple alkyne can function as the equivalent of an acyl anion nucleophile in intramolecular cyclizations with N-acyliminium ion electrophiles. The 15 cyclocondensation substrates were prepared in three stages from N-(trimethylsilyl) lactams. First a side chain nucleophile was incorporated by alkylation of lithium N-(trimethylsily1) lactam enolates (Table I). These lactams were N-acylated (Table II), and the resulting mixed imides were selectively reduced (Table III) to provide the a-alkoxy-N-(acyloxy)pyrrolidine, -piperidine, and -azepine cyclization substrates. The new methods developed during this investigation for preparing a-alkoxy N-carbamates are likely to be of general utility for accessing these N-(acyloxy)iminium ion precursors. © 1990, American Chemical Society. All rights reserved.