Chemistry Reference
In-Depth Information
polarity.
32
As a consequence of a less rigid transition state, both the reaction
eciency and the stereoselectivity diminish significantly in polar media.
33
In this context, the use of the HSBM technique can be highly convenient,
since the formation of the desired hydrogen bonding is more ecient under
solvent-free conditions. Thus, the development of asymmetric Michael re-
actions under the HSBM technique is a very promising area of study.
The first study in this topic was conducted by
ˇ
ebesta et al. who examined
the asymmetric Michael reaction between aldehydes and b-nitrostyrene in
solvent-free conditions under HSBM with catalysis by chiral pyrrolidine de-
rivatives.
34
In particular, a,a-diphenylprolinol trimethylsilyl ether (7) gave
the desired Michael products in yields in the range 44-97%, and with dia-
stereoselectivities that reached 95 : 5 diastereomeric ratios, and good enan-
tioselectivities (62-94% ee) (Scheme 4.5). A salient observation is that by
employing HSBM the yields of the reaction can be quantitative after just 1 h
reaction time, which corresponds to a reduction of more than twenty times
in the reaction time required under the best conditions in solution em-
ploying organocatalyst O-lauroyl-trans-4-hydroxyproline (Scheme 4.5).
34
Recently, Xu and co-workers reported the use of chiral squaramide de-
rivatives as hydrogen bonding donor catalysts for the Michael addition
reaction of 1,3-dicarbonyl compounds with nitroolefins under solvent-free
conditions using a planetary ball-mill. The importance of carrying out the
reaction in the absence of solvents was evident as only 0.5 mol% of the
organocatalyst was required to successfully perform the asymmetric reaction
between 2,4-pentanedione and various aromatic b-nitrostyrenes.
35
Indeed,
after only 5-25 min of reaction, the desired adducts were obtained in good
yields (63-95%), good diastereoselectivities (up to 84 : 16 dr) and excellent
enantioselectivity (91-99% ee). It was concluded that HSBM did improve the
performance of the organocatalyst relative to the reaction in solution
(Scheme 4.6).
35
Interestingly, application of grinding with a mortar and pestle in the
highly stereoselective Michael addition of trisubstituted b-ketoesters to
nitroalkene derivatives was recently reported by Chimni's group.
36
R
2
O
O
7
(20 mol%
)
HSBM
rt,
1h
NaHCO
3
(20 mol%)
NO
2
+
R
2
H
H
R
1
R
1
NO
2
1.1 equiv
1.0 equiv
Yield
44 - 97 %
dr
51:49 - 95:5
Ph
Ph
ee
62 - 94 %
H
OTMS
7
Scheme 4.5 Asymmetric Michael addition organocatalyzed by a,a-diphenylprolinol
trimethylsilyl ether (7) in a ball-mill.
34
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