Palladium(0)-Catalyzed Stereoselective Cyclization of Allenenes:  Divergent Synthesis of Pyrrolidines and 3-Azabicyclo[3.1.0]hexanes from Single Allenenes

Abstract

Two novel palladium(0)-catalyzed cyclizations of allenenes are described. Treatment of allenenes such as N-(1-alkyl-2,3-butadienyl)-N-allylsulfonamide with an aryl halide and K(2)CO(3) in the presence of a catalytic amount of Pd(PPh(3))(4) in dioxane affords 2,3-cis-pyrrolidines in a stereoselective manner. In sharp contrast, cyclization of the same allenenes using catalytic Pd(2)(dba)(3) x CHCl(3) in the presence of allyl methyl carbonate in CH(3)CN leads to stereoselective formation of a 3-azabicyclo[3.1.0]hexane framework in moderate yields.

A Short Synthesis of Aphanamol I in Both Racemic and Enantiopure Forms

“…Our initial studies focused on developing a synthesis of aphanamol I in racemic form so that we could determine the effectiveness of the previously unreported oxidative radical cyclization of 4,6‐heptadienyl malonates for the synthesis of vinyl‐substituted [3.3.0]‐bicyclic lactones. The synthetic route to racemic aphanamol I (±)‐ 1 began with the conjugate addition of (trimethylsilyl)acetylene 7 to the unsaturated malonate 6 to give (±)‐ 8 in 94 % yield using the procedure of Ohno and Tanaka (Scheme ). Krapcho decarboxylation of the malonate (±)‐ 8 gave the ester (±)‐ 9 , which, on reduction with lithium aluminum hydride, provided the primary alcohol (±)‐ 10 in good yield.…”

Synthesizing Allenes Today (1982-2006)

“…This homologation reaction is commonly used to access a wide variety of functionalized monosubstituted allenes, 22,37,[148][149][150][151][152][153][154][155][156][157][158][159] such as allene-substituted alcohols, 153,[160][161][162][163][164][165][166][167][168][169][170][171] amides, 120,172 carbamates, 92,173,174 and lactams. 175,176 Crews and co-workers, 177 R = H , a l k y l , P h R 1 = H , a l k y l R 2 = a l k y l , a l k e n y l -7…”

Development of Useful Reactions Involving Tandem Cyclizations Based on the Novel Reactivities of Allenic Compounds

“…In addition, the predominant formation of 2,4-cis-azetidines would also be influenced by palladium(0)-catalyzed isomerization. 69) [70][71][72] Allenes of general type 53, which bears a nucleophilic moiety such as a nitrogen or oxygen-containing functional group, are a well-known class of compounds that undergo a variety of palladium(0)- catalyzed cyclizations to form cyclic products 55 or 56 (Chart 9). [37][38][39][40][41][42][43][44][45] In sharp contrast, however, palladium-catalyzed reactions of allenes that contain an additional multiple bond have scarcely been studied.…”

“…Although we suffered from lower reactivity of chloropyrazine in the reaction with 83, this problem has been overcome by using iodopyrazine (entry 4) to give 107 in 62% yield. 71,113) 3-Azabicyclo[3.1.0]hexane is a basic structure of biologically active natural products 114) such as CC-1065, duocarmycin, and indolizomycin, and also a framework of a pharmacologically important class of compounds such as 3,4-methanoprolines, 115,116) poly-L-proline type II peptide mimetics, 117) and conformationally rigid analogues of [1,4Ј-bipiperidine]-4Ј-carboxamides (Fig. 2).…”