Efficient and Practical Method for Synthesizing N-Heterocyclic Compounds Using Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by Ti(O- i -Pr) 4 /2 i -PrMgX Reagent. Synthesis of Quinolones, Pyrroles, Indoles, and Optically Active N-Heterocycles Including Allopumiliotoxin Alkaloid 267A

Treatment of N -(2- or 3-alkynyl)amino esters with a low-valent titanium reagent diisopropoxy(η 2 -propene)titanium ( 1 ), generated in situ by the reaction of Ti(O- i -Pr) 4 and 2 i -PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford α-alkylidene-pyrrolidinones or -piperidinones. Thus, treatment of N -propargyl-anthranilates 5, -indole-2-carboxylates 10, or -pyrrole-2-carboxylates 13 with 1 gave 4-quinolones 7, [1,2 -a ]indoles, or [1,2 -a ]pyrroles, respectively. Similarly, N-alkynylated α- or β-amino esters 14 or 15 with 1 afforded N-heterocycles 18 or 19 . In the reaction of N -(2- or 3-alkenyl)amino esters with 1, the resulting INAS product underwent intramolecular carbonyl addition (ICA) reaction to afford the N-heterocyclic compounds having a cyclopropanol moiety in good to excellent yields. Thus, the treatment of N -alkenyl-anthranilate 4a, -indole-2-carboxylates 8 and 9, or -pyrrole-2-carboxylates 11 and 12 with 1 gave the corresponding quinoline derivative 6a, [1,2 -a ]indoles, or [1,2 -a ]pyrroles, respectively. The optically active N-heterocyclic compounds 20 and 21 were obtained from N-alkenylated α- or β-amino esters 16 or 17 . A highly efficient total synthesis of allopumiliotoxin alkaloid 267A has also been accomplished. Thus, the N -propargyl-2[(1-hydroxy-1-methoxycarbonyl)ethyl]pyrrolidine 24 (from l -proline in six steps) reacted with 1 to afford the corresponding indolidinone 25 in 67% yield, which has previously been converted to allopumiliotoxin 267A.