Ti^IV-Mediated Reactions between Primary Amines and Secondary Carboxamides:  Amidine Formation Versus Transamidation

Abstract

Titanium(IV)-mediated reactions between primary amines and secondary carboxamides exhibit different outcomes, amidine formation versus transamidation, depending on the identity of the TiIV complex used and the reaction conditions employed. The present study probes the origin of this divergent behavior. We find that stoichiometric TiIV, either Cp*TiIV complexes or Ti(NMe2)4, promotes formation of amidine and oxotitanium products. Under catalytic conditions, however, the outcome depends on the identity of the TiIV complex. Competitive amidine formation and transamidation are observed with Cp*TiIV complexes, generally favoring amidine formation. In contrast, the use of catalytic Ti(NMe2)4 (< or =20 mol %) results in highly selective transamidation. The ability of TiIV to avoid irreversible formation of oxotitanium products under the latter conditions has important implications for the use of TiIV in catalytic reactions.

Recent Developments in Amide Synthesis: Direct Amidation of Carboxylic Acids and Transamidation Reactions

“…[44] Interestingly, in this case the reactions with aniline as the nucleophile were particularly efficient. [45,48] We have reported that B(OCH 2 CF 3 ) 3 is an effective reagent for the transamidation of primary amides to secondary amides (Scheme 20). [45,48] We have reported that B(OCH 2 CF 3 ) 3 is an effective reagent for the transamidation of primary amides to secondary amides (Scheme 20).…”

Transamidation of Primary Amides with Amines Using Hydroxylamine Hydrochloride as an Inorganic Catalyst

“…Several metal complexes have been reported to promote transamidation reactions in the last two decades, including AlCl 3, 7 Sc(OTf) 3 ,8 Ti(NMe 2 ) 4 9 and polymer‐bound HfCl 4 10. Lanthanide catalysts have been reported to promote transamidation between Fmoc protected lactams and various amines 11.…”

Transamidation of Primary Amides with Amines Using Hydroxylamine Hydrochloride as an Inorganic Catalyst

“…There are several reports of thermal transamidation reactions, [4] typically requiring very high temperatures (> 180 8C), thus having a very limited substrate range. The use of the yeast Candidia cylindracea lipase has been reported by Gotor et al to promote transamidations between Ntrifluoroethyl-2-chloropropionamide and various amines [5] and intramolecular transamidations have been reported by Langlois and Buchwald et al [6] Several metal complexes have been reported to promote transamidation reactions in the last two decades, including AlCl 3, [7] Sc(OTf) 3 , [8] Ti(NMe 2 ) 4 [9] and polymer-bound HfCl 4 . [10] Lanthanide catalysts have been reported to promote transamidation between Fmoc protected lactams and various amines.…”