Chemistry Reference
In-Depth Information
Use of catalytic olefi n metathesis in enantioselective synthesis has thus far largely
concerned reactions of enantiomerically enriched substrates with achiral catalysts [1];
catalytic enantioselective olefi n metathesis allows access to enantiomerically enriched
molecules that cannot be readily prepared through the above, and commonly practiced,
strategy (see below for specifi c examples). Unlike most enantioselective transforma-
tions, olefi n metathesis, which entails the formation and cleavage of C-C double bonds,
does not involve the direct formation of an
sp
3
- hybridized stereogenic center. Instead,
stereochemistry is established indirectly, frequently by desymmetrization of an achiral
substrate (Scheme 8E.3), wherein the chiral catalyst must discriminate between enan-
tiotopic groups or sites of the molecule [3]. Consequently, the products obtained would
be diffi cult to synthesize through other enantioselective protocols (i.e., formation of a
stereogenic center, followed by olefi n metathesis with an achiral catalyst).
Achiral substrates
Meso -achiral substrates
OBn
OBn
Ru or Mo
catalyst
Ru or Mo
catalyst
Me
O
Me
Me
O
O
Ph
O
Me
Ph
Scheme 8E.3.
Desymmetrization in catalytic enantioselective olefi n metathesis.
Detailed reviews of catalytic enantioselective olefi n metathesis through 2003 have
appeared [4]. This chapter will therefore focus on the developments that have been
disclosed since the appearance of the above reports.
8E.2. ENANTIOSELECTIVE RING - CLOSING
METATHESIS ( RCM ) REACTIONS
8E.2.1. Ru - Catalyzed Enantioselective RCM
8E.2.1.1. The Catalytic Enantioselective Method
Ring - closing metathesis (RCM) is
the most commonly used version of olefi n metathesis in organic synthesis. While achiral
Ru catalysts are widely employed for non-enantioselective RCM, mostly due to ease of
handling, enantioselective RCM has largely been dominated by chiral Mo-based alkyli-
denes. Through 2001, there had been only one report of Ru-catalyzed enantioselective
RCM [5]. Since 2002, however, a number of chiral Ru catalysts have been discovered to
promote RCM. Several notable fi ndings are summarized in Table 8E.1 and compared
with the optimal Mo catalyst [6,7].
The state of the art in Ru-catalyzed enantioselective RCM is signifi cantly less devel-
oped than the Mo-catalyzed variants (see Table 8E.1). Limited substrate scope is mani-
fest upon comparison of entries 2-4 with 6-7 and 9-10 with 11-13 in Table 8E.1. Unlike
Mo-based complexes, which readily promote enantioselective RCM of all substrates in
Table 8E.1 (entries 1, 5, and 8), Ru complexes surveyed are restricted to desymmetriza-
tions of trienes bearing trisubstituted
E
- olefi ns. For example, Ru complex
7b
can be used
to catalyze enantioselective RCM of the triene in entry 6 but fails to approach the same
level of selectivity in entry 2 [5]; the same is true of the complex
13
(entry 7 vs. 4). To
date, the highest enantioselectivity for Ru-catalyzed desymmetrization of the triene in
