Efficient catalytic asymmetric alkylations. 3. A kinetic and mechanistic study of the enantioselective phase-transfer methylation of 6,7-dichloro-5-methoxy-2-phenyl-1-indanone

Abstract

The phase-transfer methylation of 6,7-dichloro-5-methoxy-2-phenyl-l-indanone by MeCl in 50% NaOH/toluene using substituted N-benzylcinchoninium halides has provided the methylated indanone 2 in ee's up to 94%. The effects of solvent, alkylating agent, temperature, and catalyst were investigated: nonpolar solvents gave higher ee's than polar solvents; MeCl gave a higher ee than did MeBr and Mel; and temperature had little effect on the reaction. A Hammett plot of log ee/ee0 vs. a for the N-benzylcinchoninium halide catalysts gave a reaction constant p of 0.21 with an ee range of 60% to 94%, demonstrating that substituents with increasing electronwithdrawing power improve catalyst selectivity. A kinetic and mechanistic study of the reaction has revealed several unusual features. In 50% NaOH/toluene these include the following: (1) the indanone 1 is deprotonated at the interface to form the sodium enolate as a separate solid phase; (2) the substituted IV-benzylcinchoninium catalysts are extracted into the organic layer as dimers; and (3) the kinetic order in MeCl is 0.7 and in catalyst is 0.55. In 30% NaOH/toluene the following obtain: (1) no solid enolate is formed; (2) an order in catalyst of 0.5 was found for the chiral methylation pathway, while an order of 1.0 was found for the racemic methylation pathway.

Enantioselective synthesis of the fragrance trans-magnolione under asymmetric phase transfer catalysis

“…Both reactions did not afford total conversion of the product and did not proceed further after 7 days. It has in fact to be taken into account that Cinchona-derived ammonium salts with a free hydroxyl function, like the present ones, can undergo rearrangements and decomposition when left for prolonged time in basic conditions [15]. Therefore, due to such decomposition, the amount of catalyst decreases progressively, then slowing down the reaction.…”

Enantioselective Organocatalysis

“…[139] Furthermore, it was demonstrated that substrates with stronger electron-withdrawing substituents on the adjacent position increase the catalyst selectivity. [140] In particular, the alkylation of the tert-butylglycinatebenzophenone Schiff base, [143] which is considered to form a tight catalyst ± substrate complex, gave impressive results. A series of natural and unnatural a-amino acid derivatives were prepared with enantioselectivities of up to 400:1 by using catalyst 46 d (Scheme 39).…”

Rhodium complexes with chiral counterions: achiral catalysts in chiral matrices

“…(1)) and (R)-acetylphenylalanate (3) (Eq. (2)) in presence of an excess of norbornadiene (NBD) to afford the neutral (1S)-10-camphorsulfonato and (R)-N-acetylphenylalanato Rh(I) complexes 2 and 4, respectively. Both complexes were soluble in aliphatic and ether solvents.…”

“…In the 1980s chiral ammonium salts were shown to act as enantioselective phase transfer catalysts in a number of organic transformations [1,2] and recently optical yields of up to 99% have been achieved [3]. Moreover, it was demonstrated that chiral spectator ions also induce chirality in the course of reactions catalyzed by achiral metal complexes.…”