Ph.D. Thesis_AS_Publishing version for IRC_12 ... - Jacobs University

Chapter 1
1.4.3 Asymmetric Michael addition to nitroolefins
List in 2001 15 demonstrated for the first time the asymmetric Michael additions of different
unmodified ketones to nitroolefins (Scheme 1.7). He got high yields (up to 94%) and
diastereoselectivities (>20:1) but the ee was very poor (maximum 23%).
Aldehydes as Michael donors in catalytic asymmetric Michael additions were pioneered by
Barbas group (Scheme 1.14). 34 They used catalyst 33 (Figure 1.5) for this study and had up to
96% yield with 98:2 dr and 78% ee.
H
O
R
R'
NO 2
33 (20 mol%)
THF, rt
H
O
R
R'
NO 2
R = alkyl
R' = alkyl, aryl
Yields = 42 to 96%
drs = 85:15 to 98:2
ees = 56 to 78%
Scheme 1.14. First example of catalytic asymmetric Michael addition of aldehydes to
nitroolefins.
After these two reports, organocatalytic asymmetric Michael addition of aldehydes and ketones to
nitroolefins is presently further developed. Figure 1.9 represents ketones that have been examined
in asymmetric Michael additions. A commonly used electrophile is trans-β-nitrostyrene (Figure
1.10), however a variety of electrophiles can be used. Among the examined ketones (Figure 1.9),
cyclohexanone (Figure 1.9, 50) is the most common nucleophile and excellent results in terms of
ee, dr, yield, reaction time, temperature and catalyst loading are possible (as shown in Table 1.2).
Despite the fact that ketones are common in asymmetric Michael additions, some of these are still
challenging for the reported catalysts (e.g cyclopentanone 51, Figure 1.9). For a complete
comparison of the product profile given by cyclohexanone and cyclopentanone, see Table 1.2 and
Table 1.3.
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