General and Efficient Insertions of Carbons Carrying Aryl and Heteroaryl Groups:  Synthesis of α-Aryl- and α-Heteroaryl-Substituted Ketones

Abstract

Anions formed from the lithiation of a variety of 1-(arylmethyl)- and 1-(heteroarylmethyl)benzotriazoles 1 with n-BuLi underwent addition to aliphatic and aromatic aldehydes and cyclic and acyclic ketones. Subsequent in situ thermal rearrangements of the intermediates in the presence of zinc bromide provided one-carbon chain-extended or ring-expanded alpha-aryl- and alpha-heteroaryl-substituted ketones 2 in moderate to excellent yields in simple one-pot operations with excellent regioselectivity in most cases. Substituent effects on the relative migration rates were investigated in the insertion reactions of 1-(4-methoxybenzyl)benzotriazole (1e) with XC(6)H(4)COPh. The small and negative Hammett rho(+) value (-0.92) suggested that the rearrangements proceed via early, reagent-like, electron deficient transition states.

Efficient Syntheses of Secondary and Tertiary 2-Aryl- and 2-Heteroaryl-allyl Alcohols

“…The fact that the preparation of 3i necessitated quite harsh reaction conditions is puzzling since steric factors cannot be invoked to explain this finding. The electron-donating 4-( N , N -dimethylamino)phenyl is known to facilitate the ionization of the benzotriazole; therefore, this reaction is controlled by conformational rather than electronic factors. In the case of 1f (X = SPh), the phenylthio group is a better leaving group than benzotriazole; consequently the benzotriazolyl moiety is retained in the allyl ether product 4 .…”

Functionalized (Benzotriazol-1-yl)methanes as 1,1-Dipole Synthon Equivalents in Diverse Annulations to Aromatic and Heteroaromatic Rings

“…Earlier work from our laboratory revealed 1-phenylthiomethylbenzotriazole to be a valuable annulating reagent for the synthesis of phenylthio-substituted carbocyclic compounds . We have also demonstrated that a wide range of functionalized (benzotriazol-1-yl)methanes (Scheme ) are excellent reagents for insertion of carbon into aldehydes and ketones, due to the ease with which the corresponding carbanions can be generated, together with the facile removal of the benzotriazolyl group to form carbocations . In that work, a wide variety of functionality could be introduced, attached to the carbon atom inserted.…”

1,2,3-Triazoles

“…Additions of anions 400 to carbonyl groups of aldehydes or ketones produce anions 411 that upon treatment with ZnBr 2 eliminate benzotriazole at elevated temperature and rearrange to ketones 412 ( Scheme 67 ) <1996JOC7571> . This insertion of carbons carrying aryl or heteroaryl substituents provides a convenient method for one-carbon chain extension or ring expansion for aldehydes and ketones.…”