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

Chapter 1
and 2 in Table 1.2). The enamine formed from is a good nucleophile and readily allows the
reaction to proceed even by using low stoichiometry of cyclohexanone (Entries 3 and 4 in Table
1.2). All the catalysts used in Table 1.1 are proline based except for one (catalyst 26, Figure 1.4)
which is a chiral bispidine-based catalyst. 35 This organocatalyst contains a primary-secondary
diamine template. The primary amine of the catalyst (26, Figure 1.4) attacks the carbonyl to make
an enamine in the presence of 3,3,5,5-tetrabromobiphenol (additive). In the transition state, one
of the hydrogen atoms of the hydroxyl group of TBBP participates in intramolecular H-bonding
and another is free to protonate the secondary amine of 26 and to activate the nitroalkenes by H-
bonding. All the results in Table 1.2 show that cyclohexanone is no longer a challenging ketone,
but can be used as a model substrate for Michael addition to nitroolefins.
Table 1.2: Top 10 references about Michael addition of cyclohexanone to nitroolefins.
O
Ph
O Ph
O Ph
NO 2 NO 2 NO 2
organocatalyst
syn product anti product
Entry Catalyst/Loading
(mol %)
Equiv
ratio [a]
Time
(h)
Temp
[ o C]
Yield
(%)
dr
(syn/anti)
ee
(%)
1 33 49 / 15 5 16 rt 99 99 : 1 99
2 30 29 / 10 4 24 rt 98 99 : 1 99
3 36 37 / 20 2 12 rt 95 98 : 2 99
4 25a 11 / 20 1 38 0 o C 93 96 : 4 90
5 35 26 / 10 20 12 rt 99 98 : 2 98
6 28 27 / 10 2 48 25 o C 99 98 : 2 97
7 26 21 / 20 10 10 0 o C 96 50 : 1 97
8 37 31 / 10 20 22 rt 99 99 : 1 93
9 29 28 / 10 20 8 0 o C 99 98 : 2 93
10 38 43 / 10 5 16 rt 100 96 : 4 91
[a] Equivalent ratio of cyclohexanone to nitroolefins.
27