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

Chapter 1
1.4.2.2 Thiourea based bifunctional catalysts
Thiourea is an important building block in the design of bifuncational organocatalysts. The
presence of static-double hydrogen bonding site on thiourea moiety makes it useful in the design
of thiourea based bifunctional organocatalysts. Figure 1.3 shows some examples of thioureabased
catalysts used for asymmetric Michael additions. 25 All these thiourea based catalysts are
acting on the same principle of a bifunctional catalyst. A primary or secondary nitrogen on the
catalyst attacks on the carbonyl carbon, converting them into chiral enamines. Meanwhile, the
thiourea unit attracts the electrophile (nitroolefin or maleimide) through a hydrogen bond
interaction. Here, I will explain shortly the catalytic activities of two catalysts from Figure 1.3.
Tang and coworkers 25a used a thiourea-based organocatalyst for the addition of ketones (cyclic
and acyclic) and isobutyraldehyde to nitroolefins. They combined two well-known moieties,
pyrrole and thiourea in close proximity to make an effecient organocatalyst (Figure 1.3, 11). With
this specially designed catalsyt they obtained upto 99% yield, 99:1 dr and 98% ee when using
cyclohexanone as Michael donor. However, their catalyst showed only a mediocre result when
using cyclopentanone as Michael donor. With cyclopentanone, 20 mol% loading of catalyst 11
reached only to 27% yield, 75:25 dr and 71% ee in a reaction of 60h. They also got a mediocre
result with isobutyraldehyde addition to trans-β-nitrostyrene (20 mol% loading of catalyst 11,
61% yield and 82% ee).
Wang and coworkers, in 2010, 25c reported asymmetric Michael addition of aldehydes
(unsubtituted and α-substituted) to maleimides using a thiourea-based catalyst (Figure 1.3, 14).
Their catalsyt showed brilliant results with unsubstituted aldehydes or less sterically hindered α-
substituted aldehydes (e.g isobutyraldehyde). For cyclopentanecarboxyaldehdye and
cyclohexanecarboxyaldehyde addition to maleimides, they increased their catalyst loading from 1
mol% to 15 mol% and obtained only 69% and 72% yields, with 96% ee and 95% ee,
respectively.
All the remaining catalysts in Figure 1.3 work on the same common principle of a bifunctional
catalyst.
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