Organocatalyzed Formal [2 + 2] Cycloaddition of Ketimines with Allenoates: Facile Access to Azetidines with a Chiral Tetrasubstituted Carbon Stereogenic Center

Abstract

An enantioselective organocatalyzed aza-MBH-type reaction of ketimines and allenoates has been developed. The present formal [2 + 2] cycloaddition produces highly functionalized azetidines with a chiral tetrasubstituted carbon stereogenic center in good to excellent yields and high enantioselectivities.

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…[4] Other strategies accomplish ring and stereocenter construction simultaneously by uniting two fragments;however, this often leads to difficulty in establishing the correct regio-and stereochemistry (Scheme 1B). The [2+ +2] reactions have been well-explored [6] while the corresponding [3+ +1] reactions are less common, although N-atom transfer from an oxaziridine to ad onor-acceptor cyclopropane was recently disclosed, as well as two examples of nucleophilic aziridine opening with sulfoxonium or nitrogen ylides. [7,8] Despite these advances,s tereoselective access to highly substituted, densely functionalized azetidines remains difficult.…”

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…[5] Theincreased interest in azetidines requires new synthetic approaches to access desired scaffolds with varied substitution and stereochemistry.T raditional methods employ cyclization of al inear precursor via a4 -exo-tet substitution, but are limited in scope. The [2+ +2] reactions have been well-explored [6] while the corresponding [3+ +1] reactions are less common, although N-atom transfer from an oxaziridine to ad onor-acceptor cyclopropane was recently disclosed, as well as two examples of nucleophilic aziridine opening with sulfoxonium or nitrogen ylides. The [2+ +2] reactions have been well-explored [6] while the corresponding [3+ +1] reactions are less common, although N-atom transfer from an oxaziridine to ad onor-acceptor cyclopropane was recently disclosed, as well as two examples of nucleophilic aziridine opening with sulfoxonium or nitrogen ylides.…”

Recent advances in synthetic facets of immensely reactive azetidines

“…Yadav and co-workers 43 43 Sasai and co-workers 44 have developed an enantioselective synthesis of azetidines 156 using aza-Morita-Baylis-Hillman (MBH) reaction of ketimines 154 and allenoate 155 in the presence of organocatalyst. The reaction was optimized using range of chiral amines as organocatalysts with the best results in terms of yields were obtained using b-isocupreidine (b-ICD) as catalyst in the presence of MS 3Å.…”