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

Chapter 1
amine carrying a thiourea moiety are mixed, acid-base reaction occurs to form an ammonium
salt. The ionic interaction between the ammonium cation and the carboxylate causes these two
modules to self-assemble, forming a catalyst system. They used different modules and found that
quinidine-thiourea matched with L-phenylglycine and formed a model organocatalyst. They
catalyzed the Michael addition of different cyclic and acyclic ketones to nitroolefins and obtained
upto 92 % yield, 96:4 dr and 99 % ee but under the same set of conditions cyclopentanone gave
poor diastereoselectivity and yield (Table 1.3, entry 4).
Feng and coworkers 35 used a chiral bispidine-based catalyst (26, Figure 1.4) for asymmetric
Michael additions. They suggested that a primary-secondary diamine template on bispidine could
serve through an enamine activation and H-bonding interaction. With the addition, of, acyclic
ketones to nitroalkenes they achieve upto 99 % yield and 99 % ee. In the addition of
cyclohexanone to various nitroalkenes they obtained upto 99 % yield, 98:2 dr and 99 % ee.
Under their optimized conditions, cyclopentanone showed a poor result (Table 1.3, entry 12, 85%
yield, 48:52 dr, 26% ee), which was an indication of the limits of their catalyst's activity.
In conclusion, results in Table 1.3 show that cyclopentanone is still difficult and overcoming this
challenge may be possible by designing a proper catalyst. Even recent attempts to solve this
problem are not successful in a practical reaction. 44
Table 1.3: Top 12 references about Michael addition of cyclopentanone to trans-β-nitrostyrene.
O
Ph
O Ph
NO 2 organocatalyst
syn product anti product
NO 2
O Ph
NO 2
Entry Catalyst/Loading Equiv Time Temp Yield dr ee (%)
(mol %) ratio [a] (h) [ o C] (%) (syn/anti)
1 39 5 / 10 3 26 rt 80 90 : 10 98 [b]
2 36 37 / 20 2 156 rt 88 83 : 17 95 [b]
3 40 32 / 10 8 30 rt 85 80 : 2 83 [b]
29