Page 159 - Advanced Organic Chemistry Part B - Reactions & Synthesis

H H 131

N N N N SECTION 2.1
H Sn Sn Aldol Addition and
C 2 5 C H O SCF 3
3
O SCF 3 2 5 CH Ph Condensation Reactions
3
CF SO 3 O 2
3
O H O H
TBSO EtS
H
SEt R R
H OTMS
OTMS
open TS leading to syn product chelated TS leading to anti product
White and Deerberg explored this reaction system in connection with the synthesis of
a portion of the structure of rapamycin. 165 Better yields were observed from benzyloxy
than for a methoxy substituent, and there was a slight enhancement of stereoselectivity
with the addition of ERG substituents to the benzyloxy group.

OTMS O OH
O CH Sn(OTf) 2 C
C H S + CH 3 C H S CH 3
2 5
2 5
OR CH 3 21 OR CH 3
R syn:anti e.e.
CH O 70:30 87
3
PhCH O 85:15 93
2
PMB 90:10 96
2,4-DMB 95:5 92

Scheme 2.8 gives some examples of chiral Lewis acids that have been used to catalyze
aldol and Mukaiyama reactions.
Scheme 2.9 gives some examples of use of enantioselective catalysts. Entries 1 to
4 are cases of the use of the oxazaborolidinone-type of catalyst with silyl enol ethers
and silyl ketene acetals. Entries 5 and 6 are examples of the use of BINOL-titanium
catalysts, and Entry 7 illustrates the use of Sn OTf in conjunction with a chiral
2
amine ligand. The enantioselectivity in each of these cases is determined entirely by
the catalyst because there are no stereocenters adjacent to the reaction sites in the
reactants.
A different type of catalysis is observed using proline as a catalyst. 166 Proline
promotes addition of acetone to aromatic aldehydes with 65–77% enantioselectivity.
It has been suggested that the carboxylic acid functions as an intramolecular proton
donor and promotes reaction through an enamine intermediate.

165 J. D. White and J. Deerberg, Chem. Commun., 1919 (1997).
166
B. List, R. A. Lerner, and C. F. Barbas, III, J. Am. Chem. Soc., 122, 2395 (2000); B. List, L. Hoang,
and H. J. Martin, Proc. Natl. Acad. Sci., USA, 101, 5839 (2004).