Synthesis of Simple 3,3-Diarylazetidines from N-Boc-3-arylazetidinols Using Friedel–Crafts Arylation Conditions

Abstract

A synthesis of 3,3-diarylazetidines from N-Boc-3-aryl-3-azetidinols using Friedel–Crafts arylation conditions with AlCl3 is described. A series of substituted diarylazetidines were readily prepared and isolated as the oxalate salts in high yield and high purity. The 3,3-diarylazetidine oxalates were then easily converted into N-alkyl and N-acyl analogues (RX, NaHCO3/DMF/100 °C) in high overall yields.

Synthesis of oxetane and azetidine ethers as ester isosteres by Brønsted acid catalysed alkylation of alcohols with 3-aryl-oxetanols and 3-aryl-azetidinols

“…1b). 17–19,20 Lewis acid catalysts (Li + , Ca 2+ and Fe 3+ salts) were successful for selective alcohol activation for Friedel–Crafts alkylation reactions and reactions with thiols. Interestingly, in the Friedel–Crafts reaction with phenols, aryl oxetane ethers were identified as reversible off-cycle intermediates.…”

Deconstructive isomerization of azetidinols via C–C bond cleavage enabled by N-heterocyclic carbene (NHC) catalysis

“…1 For years, much work has been devoted to the synthesis of azetidines, 2 whereas the transformation of azetidines acting as building blocks in organic synthesis has been less developed. 3–6 The current research work mainly focuses on the ring-opening of azetidines through the cleavage of the C–N or C–C bond. As with aziridines, 7 the C–N bond cleavage is easily achieved through a nucleophilic substitution reaction via an azetidinium salt intermediate (Scheme 1a).…”