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Mechanistic Studies on Stereoselective Organocatalytic Direct beta-C-H Activation in an Aliphatic Chain by Chiral N-Heterocyclic Carbenes

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Title Mechanistic Studies on Stereoselective Organocatalytic Direct beta-C-H Activation in an Aliphatic Chain by Chiral N-Heterocyclic Carbenes
 
Creator REDDI, Y
SUNOJ, RB
 
Subject FORMAL 3+2 ANNULATION
ASYMMETRIC CATALYSIS
ACID-DERIVATIVES
STETTER REACTION
NONCOVALENT INTERACTIONS
GAMMA-BUTYROLACTONES
CARBON ACTIVATION
REACTION INSIGHTS
C(SP(3))-H BONDS
NHC CATALYSIS
N-heterocyclic carbenes
C-H bond functionalization
stereoselectivity
reaction mechanism
transition states
density functional theory
 
Description The functionalization of aliphatic and aromatic C-H bonds has remained a priority in transition-metal catalysis for the last few decades. N-heterocyclic carbenes (NHCs) have very recently been proven as an effective organocatalytic alternative toward site-selective sp(3) beta-C-H bond functionalization in aliphatic esters and related compounds. We have employed modern density functional theory computations to provide the first mechanistic insights into this entirely new form of reactivity of NHCs, leading to beta-C-H bond activation. NHC-catalyzed coupling between hydrazone and beta-phenyl propionate leading to a gamma-lactam bearing two chiral centers is reported. An interesting two-step mechanistic cascade that helps surmount the high bond dissociation energy of an otherwise inert beta-C-H bond is identified. An initial addition-elimination at the ester group installs the chiral triazolium NHC to the substrate. The deprotonation of the alpha-C-H by the departing phenoxide first furnishes an alpha-enolate intermediate. A concerted protonation at the enolate oxygen by the phenol and a beta-C-H deprotonation by the phenoxide leads to the vital nucleophilic beta-carbanion intermediate. The origin of enantioselectivity in the C-C bond formation between the si prochiral face of the nucleophilic beta-carbon and the re face of electrophilic hydrazone is traced to the differential in the C-H...pi, C-H...O and N-H...O interactions that exist in the transition states for the lower energy si,re and higher energy re,si modes in the Michael addition step. The computed enatio- and diastereoselectivities are in very good agreement with those in an earlier experimental report.
 
Publisher AMER CHEMICAL SOC
 
Date 2016-01-15T06:18:59Z
2016-01-15T06:18:59Z
2015
 
Type Article
 
Identifier ACS CATALYSIS, 5(10)5794-5802
2155-5435
http://dx.doi.org/10.1021/acscatal.5b01870
http://dspace.library.iitb.ac.in/jspui/handle/100/17914
 
Language en