CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

Ph
OH
i
Cl
Ph
42 43 OH
Cl
96% ee
80% yield
(i) AD-mix β, NaHCO 3 , CH 3 SO 2 NH 2 , t-BuOH-H 2 O, 0 o C.
Scheme II.1.6
Asymmetric addition of organometallics to ketones:
Addition of a carbon-nucleophile to a carbonyl compound is one of the most widely
used synthetic protocols for the synthesis of carbinols through homologation. This is
generally done using organometallic reagents prepared from various metals viz. Li, Mg,
Zn, Sn etc. Amongst these, the Zn-mediated routes offer better opportunity of
stereocontrol. However, because most of the dialkyl zinc reagents are not commercially
available, the Zn-mediated reactions are primarily restricted to either
allylation/propargylation by Barbier type methods or with the commercially available
Et 2 Zn. Indeed, addition of Et 2 Zn to aldehydes in the presence of a chiral ligand is often
used to test its efficacy as a chiral auxiliary. The works carried out till 1992 on this reaction
has been reviewed. 47 The origin of the enantioselectivity of the reaction has also been
discussed, which provides references of the most successful developments in this field. 48
Although the R 2 Zn reagents react extremely sluggishly with carbonyl compounds,
effective catalysis has been achieved by coordinating these with organic ligands. The
ligand-induced activation of the R 2 Zn reagents can be explained on the basis of the
changes in geometry and bond energy of the reagents, caused by the coordination of Zn. 49ab
For example, dimethyl zinc has a linear structure with a Zn-C bond length of 1.95 Å (Fig.
II.1.2) and is not reactive towards aldehydes or ketones. However, on coordination with a
27