DEDICATED TO PROFESSOR HC BROWN ON HIS ... - Sigma-Aldrich

and 5 provided moderate ee’s in the
reduction of (E)-4-phenyl-3-buten-2-one
(Figure 6). 9 On the other hand, enantioselectivities
in the reductions of α,β-ynones
are generally very sensitive to the steric size
of the distal group of the alkyne and to the
nature of the substituents on the carbonyl
carbon. Ipc2BCl (4) provided very high ee’s
of the sterically hindered propargyl alcohols
32f and 32g, but very low ee’s of
nonsterically hindered alcohols (eq 16). 50
Similarly, reductions with 1 51 or 5 32,50 were
sensitive to steric effects. The catalytic
reductions, using 11b 52 or 12b 53 at low
temperatures, also furnished high ee’s for
hindered ketones. It was also observed that
the enantioselectivity of the CBS
oxazaborolidine reduction was dependent on
the steric size of the boron substituents in the
catalyst (eq 17). 54
3.6. α-Azido, Amino, and Imino
Ketones
Asymmetric reduction of prochiral
ketones containing nitrogen at the α position
is one of the most convenient methods for
preparing chiral β-amino alcohols, which
are found as important structural units
in many biologically active compounds.
α-Azidomethyl aryl ketones are effectively
reduced to the corresponding 2-azido-1arylethanols
in very high ee’s by the
CBS oxazaborolidine-catalyzed reduction
(eq 18). 55 In the reduction of α-N,N’dialkylamino
ketones, 4 afforded high ee’s, 56
whereas 1 provided moderate ee’s (eq 19). 57
Moreover, the catalytic reduction of α-imino
ketones has been successfully carried out
(eq 20), 58 and has been applied to the highly
enantioselective synthesis of chiral albuterol
(33) (eq 21). 59
3.7. Keto Phosphonates
Optically active α-hydroxyphosphonates
are not only biologically active as inhibitors
of different enzymes, but also serve
as precursors in the synthesis of
α-aminophosphonates, which are used as
analogs of α-amino acids. 4 reduced
aromatic α-ketophosphonates to the corresponding
α-hydroxyphosphonates with
moderate ee’s. 60 CBS oxazaborolidinecatalyzed
reduction, using 11c as the catalyst
and catecholborane as the borane carrier,
provided moderate-to-high enantioselectivities.
The reduction is also effective for β and γ
analogs (eq 22). 61
3.8. β-Keto Sulfones
Optically active β-hydroxy sulfones are
extremely useful chiral building blocks,
because the α-carbon atom can be further
VOL. 35, NO. 1 • 2002
eq 17
eq 18
eq 19
eq 20
eq 21
11