414
Another copper-based catalyst system was deployed to enable the highly chemoselective α-amination of N-acylpyrazoles which serve as the protected form of
aliphatic carboxylic acids. A series of acids were aminated at the α-position via
acylpyrazoles by means of a hypervalent iodine nitrenoid precursor, PhI=NTs [113].
Systematic mechanistic studies indicate that the weak amide conjugation and concurrent bidentate coordination promote the chemoselective enolization of acylpyrazole to react with the highly active in situ-generated copper nitrenoid species
leading to the α-aminated product (Scheme 56). Importantly, this amination technique allowed the late-stage functionalization of many bioactive compounds including a TBS-protected lithocholic acid derivative into an analogous α-amino acid
derivative (Scheme 57).
Apart from acylpyrazoles, 2-alkyl-substituted β-keto esters also undergo coppercatalyzed amination and aziridination with the hypervalent iodine nitrenoid precursor 181 towards the formation of α-acyl-β-amino acid and 2,2-diacyl aziridine
derivatives, respectively (Scheme 58) [114]. In cases of both amination and aziridination reactions, the copper catalyst triggers the β-keto ester to selectively form the
enol via bidentate coordination in a manner similar to acylpyrazoles, thereby reacting with the copper nitrenoid species.
A copper-based system, consisting of CuCl/P(tBu) 3 , was shown to activate ditert- butyldiaziridinone to generate a nitrogen coupling partner in situ for the synthesis of hydantoin derivatives via an α-amination of ester and subsequent ring closer
sequence (Scheme 59) [115]. However, this amination protocol was less effective
for bulkier esters derived from ethyl or tert-butyl alcohols.
Likewise, palladium catalysts are also reported to enable C(sp
3
)–H amination of
a tailored substrate 190 in which the enol functionality can be further stabilized via
chelation assistance. The reaction involves an intramolecular reductive cyclization
of nitroarenes through nitrosoarene intermediate in the presence of carbon
Scheme 55 Coppercatalyzed non-directed
α-amination of
carboxy esters
A. Gupta et al.
Another copper-based catalyst system was deployed to enable the highly chemoselective α-amination of N-acylpyrazoles which serve as the protected form of
aliphatic carboxylic acids. A series of acids were aminated at the α-position via
acylpyrazoles by means of a hypervalent iodine nitrenoid precursor, PhI=NTs [113].
Systematic mechanistic studies indicate that the weak amide conjugation and concurrent bidentate coordination promote the chemoselective enolization of acylpyrazole to react with the highly active in situ-generated copper nitrenoid species
leading to the α-aminated product (Scheme 56). Importantly, this amination technique allowed the late-stage functionalization of many bioactive compounds including a TBS-protected lithocholic acid derivative into an analogous α-amino acid
derivative (Scheme 57).
Apart from acylpyrazoles, 2-alkyl-substituted β-keto esters also undergo coppercatalyzed amination and aziridination with the hypervalent iodine nitrenoid precursor 181 towards the formation of α-acyl-β-amino acid and 2,2-diacyl aziridine
derivatives, respectively (Scheme 58) [114]. In cases of both amination and aziridination reactions, the copper catalyst triggers the β-keto ester to selectively form the
enol via bidentate coordination in a manner similar to acylpyrazoles, thereby reacting with the copper nitrenoid species.
A copper-based system, consisting of CuCl/P(tBu) 3 , was shown to activate ditert- butyldiaziridinone to generate a nitrogen coupling partner in situ for the synthesis of hydantoin derivatives via an α-amination of ester and subsequent ring closer
sequence (Scheme 59) [115]. However, this amination protocol was less effective
for bulkier esters derived from ethyl or tert-butyl alcohols.
Likewise, palladium catalysts are also reported to enable C(sp
3
)–H amination of
a tailored substrate 190 in which the enol functionality can be further stabilized via
chelation assistance. The reaction involves an intramolecular reductive cyclization
of nitroarenes through nitrosoarene intermediate in the presence of carbon
Scheme 55 Coppercatalyzed non-directed
α-amination of
carboxy esters
A. Gupta et al.