Page 156 - Advanced Organic Chemistry Part B - Reactions & Synthesis

128 Another effective group of catalysts is composed of copper bis-oxazolines. 154 The
chirality is derived from the 4-substituents on the ring.
CHAPTER 2
Reactions of Carbon O O
Nucleophiles with t Bu
Carbonyl Compounds O N N t Bu
OTMS Cu CH OH O
CCO CH CH + CH 3
CH 3 2 2 3 2 CF SO O OSO CF 3
2
2
3
R CH O C R
2
3
R = CH , C H
3
6 5
This and similar catalysts are effective with silyl ketene acetals and silyl thioketene
acetals. 155 One of the examples is the tridentate pyridine-BOX-type catalyst 18.
The reactivity of this catalyst has been explored using - and -oxy substi-
tuted aldehydes. 154 -Benzyloxyacetaldehyde was highly enantioselective and the
-trimethylsilyoxy derivative was weakly so (56% e.e.). Nonchelating aldehydes such
as benzaldehyde and 3-phenylpropanal gave racemic product. 3-Benzyloxypropanal
also gave racemic product, indicating that the -oxy aldehydes do not chelate with this
catalyst.

O N O
N Cu N
OTMS Ph Ph
OTf 18
PhOCH CH O + H C PhCH O CO C H
2
2
2
2 2 5
H
OC 2 5 OH
98% e.e.
The Cu-BOX catalysts function as Lewis acids at the carbonyl oxygen. The chiral
ligands promote facial selectivity, as shown in Figure 2.3.
Several catalysts based on Ti(IV) and BINOL have shown excellent enantiose-
lectivity in Mukaiyama aldol reactions. 156 A catalyst prepared from a 1:1 mixture of
BINOL and Ti O-i-Pr gives good results with silyl thioketene acetals in ether, but
4
is very solvent sensitive. 157
BINOL,
OTMS Ti(Oi Pr) OH O
RCH O + CH 2 4
)
SC(CH ) R SC(CH 3 3
3 3
4A MS
R = alkyl, alkenyl, aryl
70–90% 89 to >98% ee
The structure of the active catalyst and the mechanism of catalysis have not been
completely defined. Several solid state complexes of BINOL and Ti O-i-Pr have been
4
characterized by X-ray crystallography. 158 Figure 2.4 shows the structures of complexes
having the composition (BINOLate)Ti O-i-Pr and (BINOLate)Ti O-i-Pr .
2 6 3 10
154
D. A. Evans, J. A. Murry, and M. C. Kozlowski, J. Am. Chem. Soc., 118, 5814 (1996).
155
D. A. Evans, D. W. C. MacMillan, and K. R. Campos, J. Am. Chem. Soc., 119, 10859 (1997); D. A. Evans,
M. C. Kozlowski, C. S. Burgey, and D. W. C. MacMillan, J. Am. Chem. Soc., 119, 7893 (1997).
156 S. Matsukawa and K. Mikami, Tetrahedron: Asymmetry, 6, 2571 (1995); H. Matsunaga, Y. Yamada,
T. Ide, T. Ishizuka, and T. Kunieda, Tetrahedron: Asymmetry, 10, 3095 (1999).
157 G. E. Keck and D. Krishnamurthy, J. Am. Chem. Soc., 117, 2363 (1995).
158
T. J. Davis, J. Balsells, P. J. Carroll, and P. J. Walsh, Org. Lett., 3, 699 (2001).