286
Chemistry Letters Vol.37, No.3 (2008)
Stereoselective Insertion of Rhodium Carbenoid to Water
under Control with Intramolecular Participation of Hydroxy Group
Takashi Sugimuraà and Takao Nagai
Graduate School of Material Science, University of Hyogo, 3-2-1 Kohto, Kamigori, Ako-gun, Hyogo 678-1297
(Received December 25, 2007; CL-071432; E-mail: sugimura@sci.u-hyogo.ac.jp)
O
A chiral diazo ester having a hydroxy group in the proper
∗
R
Ph
+
δ
geometry produces an adduct with water up to 92% de upon
treatment with a rhodium catalyst. This high stereoselectivity
is attributable to the intramolecular hydrogen bond between
the internal hydroxy group and the rhodium carbenoid.
O
O
H
OR
H
= Nu– attack
= Hydrogen
bond
Rh
Rh
δ
–
Figure 1. Model for the hydroxy-assisted stereocontrolled O–H
insertion to a chiral rhodium carbene.
Metal carbenes (carbenoids) generated from the correspond-
ing diazo compounds are synthetically versatile species that are
sufficiently electrophilic to perform cycloadditions to olefins and
aromatic ꢀ-bonds, insertions to C–H and X–H, and reactions via
the ylide formation.1 A variety of stereocontrol designs have
been applied for those reactions, and many asymmetric synthe-
ses have been successfully established. An exception is the O–
H insertion reaction.2 The stereocontrol seems to be simply real-
ized by introducing a proper chiral source onto the diazo com-
pound (X or Y in Scheme 1),3 alcohol (R),4 catalyst ligand
(L),5 or two of them, but, in fact, the obtained selectivities are
relatively low. The difficulty in the stereocontrol can be attribut-
ed to the pathway via the metal-free ylide that loses the chirality
generated during the formation of the metal ylide, and as a result,
an isomeric mixture of the chiral product is produced unless ex-
tra stereocontrol occurs during the proton-transfer step. For in-
stance, sufficient stereocontrol has been achieved using chiral
copper catalysts, while the selectivities are low with currently
more popular chiral rhodium catalysts,5 indicating that the rho-
dium ylide tends to go through a metal-free ylide process. As
is, the intramolecular coordination of the hydroxy group to the
negatively charged metal part (including ligands) of the generat-
ed rhodium carbenoid is expected to fix its own conformation, to
enhance the nucleophilicity of the carbenoid, and to prevent the
elimination of the metal part (catalyst). Here, the difference in
the reactivities between the internal and external hydroxy groups
is critical. The external hydroxy group should not coordinate
to the metal part by its proton, but the nucleophilic site of the
oxygen should easily be accessible to the carbenoid carbon, in
the reverse to the roles of the internal hydroxy group.
A phenyldiazoacetate ester 1 was derived from (2R,4R)-
2,4-pentanediol.7,8 When 1 was treated with Rh2(OAc)4 or
Rh2(OCOCF3)4 in CDCl3 at room temperature, the intramolec-
ular O–H insertion product 3 was not produced at all, but several
intermolecular products were yielded according to the slow
decomposition of 1 (Scheme 2).9 However, in the presence
of a small amount of an alcohol or water,10 1 was smoothly
consumed to give the intermolecular O–H insertion product
2a–2c. The isomer ratio was determined by the 1H NMR spectra,
and the stereochemical configurations of 2b and 2c were deter-
mined by chiral HPLC after conversion to the methyl esters.
These results are summarized in Table 1.
The reaction with methanol to give 2a was performed in
high yields, but the selectivity was negligible with both catalysts
(Entry 1). Use of 2-propanol resulted in lower yields of 2b, but
the Rh2(OAc)4 catalysis in hexane resulted in 50% de (Entries 2
and 3).9 A similar selectivity (46% de) level was also observed
in the reaction of the OH-protected 1 (t-BuMe2Si analogue,
TBS-1) with Rh2(OCOCF3)4, though it gives the opposite
stereoselectivity (Entry 4). Unlike the reactions with alcohols,
the O–H insertion with water to give 2c underwent stereoselec-
tively with Rh2(OAc)4 that resulted in 82% de (Entry 5). The
high selectivity decreased in hexane or with an excess amount
of water (Entries 6 and 7), but the lower reaction temperature re-
sulted in increase up to 92% de (Entries 8 and 9).9 The reaction
a
matter of fact, the reaction of the diazoacetoacetate
(X = Y = carbonyl) is suggested to consist of a significant con-
tribution of the metal-free ylide due to the stabilization effect of
the generated anion, and is stereocontrolled after generation of
the free-ylide.6
Chiral phenyldiazoacetate esters are popular for studying
the stereoselectivity of the O–H insertion, and the maximum
diastereomeric excess of the product so far reported was 70%
de using a rhodium catalyst, and 90% de using a copper catalyst.3
In the present study, the chiral part of the diazo ester was suitably
designed for rhodium catalysis with participation of a hydroxy
group placed at a proper position as illustrated in Figure 1. That
H
O R
H
O R
N2
LnM
X
LnM
X
MLn
ROH
MLn
–N2
Achiral metal carbene
–MLn
X
Y
X
Y
Y
Y
Chiral metal ylide
OR
Ph
N2
X ° Y
Rh2L4
ROH
O
O
O
OH
O
–MLn
OH
O
H
Ph
O R
O
O
Ph
H
H
O R
Y
O R
Y
1
2a. R = Me
2b. R = i-Pr
2c. R = H
3
X
Y
X
X
Achiral metal-free ylide
Chiral product
Scheme 1.
Scheme 2.
Copyright Ó 2008 The Chemical Society of Japan
Sugimura, Takashi
