Asymmetric Organocatalytic Reactions under Ball Milling - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 89

4.2.3 Asymmetric Morita-Baylis-Hillman (MBH) Reaction
The Morita-Baylis-Hillman (MBH) reaction constitutes a useful method for
the synthesis of b-hydroxycarbonyl compounds with an a-alkylidene group. 41
The use of small organic molecules as catalysts to perform asymmetric MBH
transformations has received increasing attention over the past decade. 9 In
this context, Friˇˇi´'s group recently reported the in situ synthesis of thiourea
organocatalyst 12, which was then evaluated in the asymmetric MBH re-
action (Scheme 4.9). 42

4.2.4 Asymmetric Alkylation of Imines
Since the development of the enantioselective alkylation of O'Donnell's
Schiff bases, 43 this methodology has been widely exploited for the prepar-
ation of chiral amino acids. 44 Recently, Lamaty and co-workers used several
cinchona organocatalysts with proven eciency in amine alkylation pro-
cesses in solution and prepared various chiral amino acids by enantiose-
lective alkylation of alkylidene imines under the HSBM technique. Over a
period of 1 h under solvent-free reaction conditions, it was possible to obtain
the desired compounds with excellent yields (in the range 91-97%) and with
up to 75% ee (Scheme 4.10). 45

4.2.5 Desymmetrization of Aromatic Diamines and meso
Anhydrides by Mechanochemistry
The desymmetrization of prochiral precursors such as meso diols, diamines,
and anhydrides into non-symmetrical and/or chiral building blocks is an
important goal in synthetic organic chemistry. 46 In this context, Friˇˇi´ and

F 3 C F 3 C

NH 2

NCS

NCS

F 3 C

S S CF 3

NH
NH

NH HN

NH 2 F 3 C F 3 C

HN

NH

S

NH 2

HSBM HSBM

F 3 C

CF 3

12

O O

O OH

1 2 (20 mol% )
HSBM
rt, 24 h, LAG
DABCO (0.25 equiv)

+

H

Yield 70 %
ee

24 %

Scheme 4.9 Asymmetric Morita-Baylis-Hillman addition reaction organocatalyzed
by bis(thiourea) 12, synthesized in situ in a ball-mill. 42