New strategic reactions for organic synthesis: catalytic asymmetric C-H activation alpha to nitrogen as a surrogate for the mannich reaction.
The asymmetric C-H activation reactions of methyl aryldiazoacetates are readily induced by the rhodium prolinate catalyst Rh(2)(S-DOSP)(4) (1) or the bridged prolinate catalysts Rh(2)(S-biDOSP)(2) (2a) and Rh(2)(S-biTISP)(2) (2b). The C-H activation of N-Boc-protected cyclic amines demonstrates that the donor/acceptor-substituted carbenoids display remarkable chemoselectivity, which allows for highly regioselective, diastereoselective, and enantioselective reactions to be achieved. Furthermore, the reactions can display high levels of double stereodifferentiation and kinetic resolution. The C-H activation is caused by a rhodium carbenoid induced C-H insertion. The potential of this chemistry is demonstrated by a very direct synthesis of threo-methylphenidate.
Davies
Huw M L
HM
Contribution from the Department of Chemistry, University at Buffalo, State University of New York, Buffalo, New York 14260-3000, USA. hdavies@acsu.buffalo.edu
Venkataramani
Chandrasekar
C
Hansen
Tore
T
Hopper
Darrin W
DW
D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D005563:Formic Acid Esters / Q000737:chemistry*; D008774:Methylphenidate / Q000138:chemical synthesis; D009584:Nitrogen / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry
D000588:Amines; D000596:Amino Acids; D005563:Formic Acid Esters; C000345:t-butyloxycarbonyl group; D008774:Methylphenidate; D012238:Rhodium; D009584:Nitrogen