Page 167 - Advanced Organic Chemistry Part B - Reactions & Synthesis

The detailed mechanism of this enantioselective transformation remains under investi- 139
gation. 178 It is known that the acidic carboxylic group is crucial, and the cyclization is
believed to occur via the enamine derived from the catalyst and the exocyclic ketone. SECTION 2.2
A computational study suggested that the proton transfer occurs through a TS very Addition Reactions of
Imines and Iminium Ions
similar to that described for the proline-catalyzed aldol reaction (see page 132). 179
H C O
3
H C O
3
N +
O N
C O H OH
CO 2 –
O

Visual models, additional information and exercises on Proline-Catalyzed Aldol
Reactions can be found in the Digital Resource available at: Springer.com/carey-
sundberg.

2.2. Addition Reactions of Imines and Iminium Ions

Imines and iminium ions are nitrogen analogs of carbonyl compounds and they
undergo nucleophilic additions like those involved in aldol reactions. The reactivity
+
+
order is C=NR < C=O <
C=NR <
C=OH . Because iminium ions are more
2
reactive than imines, the reactions are frequently run under mildly acidic conditions.
Under some circumstances, the iminium ion can be the reactive species, even though
it is a minor constituent in equilibrium with the amine, carbonyl compound, and
unprotonated imine.
H
– +
O + H NR H O NR H N +
2
2
R
Addition of enols, enolates, or enolate equivalents to imines or iminium ions provides
an important route to -amino ketones.
O
OX
+ H C NR′ 1 NR′
2
R 1 CHR 2 R 2
R

178 P. Buchschacher, J.-M. Cassal, A. Furst, and W. Meier, Helv. Chim. Acta, 60, 2747 (1977); K. L. Brown,
L. Damm, J. D. Dunitz, A. Eschenmoser, R. Hobi, and C. Kratky, Helv. Chim. Acta, 61, 3108 (1978);
C. Agami, F. Meynier, C. Puchot, J. Guilhem, and C. Pascard, Tetrahedron, 40, 1031 (1984); C. Agami,
J. Levisalles, and C. Puchot, J. Chem. Soc., Chem. Commun., 441 (1985); C. Agami, Bull. Soc. Chim.
Fr., 499 (1988).
179
S. Bahmanyar and K. N. Houk, J. Am. Chem. Soc., 123, 12911 (2001).