Table 1 Asymmetric Rh(I) catalyzed addition of phenylboronic acid
to cyclohexenone
cyclohexenone. In fact, using the monosubstituted complex as
catalytic precursor R-3-phenylcyclohexanone in quantitative
yield and 88% ee is obtained, independent of the reaction
conditions; on the contrary, the use of the disubstituted
complex allows the reaction to be directed toward the forma-
tion of 1R,3R-1,3-diphenylcyclohexanol, by only increasing
the amount of phenylboronic acid and the temperature. The
generation of this product, obtained as a single diastereo-
isomer in 83% yield and 80% ee, represents a noticeable result,
because the formation of two C–C bonds in a highly enantio-
selective way is obtained, using only one reaction. Finally, the
results obtained emphasize the unique behavior of this phos-
phite that can be used at P/Rh = 1 ratio affording a mono-
substituted Rh complex able to catalyze the addition of
phenylboronic acid to cyclohexenone without a substantial
variation of enantioselectivity.
2 (3)
L* (Rh :
Entry L* ratio)
PhB(OH)2
T/1C t/h (equiv.)
Yielda (%) eeb (%)
1
2
3
4
5
6
1 (1 : 1)d
1 (1 : 2)e
1 (1 : 2)e
1 (1 : 1)d
RT
RT
60
8
5
2
8
24
96
2
2
3
3
2
2
100 (—)
94 (6)
17 (83)
83 (—)
94 (—)
—
88 (—)
90 (80)c
88 (80)c
88 (—)
91 (—)
—
60
1b (1 : 1)d RT
1a (1 : 1)d RT
a
b
Isolated yield. Determined by HPLC analyses on Chiralcel OD-H,
220 nm, 1.0 mL minÀ1, hexane–2-propanol 99 : 1. 99.9 % Diaster-
eoisomeric excess determined by NMR.15 d Precatalyst was formed by
stirring the dioxane mixture of [{RhCl(C2H4)2}2] and L* for
c
This work was supported by University of Pisa and by
MIUR-PRIN 2006–2007 (T.F.). Mr Marco Martinelli is grate-
fully acknowledged for SEC measurements.
e
24 h. Precatalyst was formed by stirring the dioxane mixture of
[{RhCl(C2H4)2}2] and L* for 0.5 h.
Notes and references
enantioselectivity affording R-3-phenylcyclohexanone in
quantitative yield and 88% ee after 8 h (entry 1). The
disubstituted complex gives a faster and slightly more enan-
tioselective reaction, affording the product in 94% yield after
5 h, with 90% ee (entry 2). The slightly lower yield is due to the
formation of a small amount of the double addition by-
product 3,15 obtained with complete diastereoselectivity and
80% ee. When the reaction was performed in the presence of
the disubstituted complex and with an excess (3 equiv.) of
phenylboronic acid at 60 1C (entry 3), the main product was
1R,3R-1,3-diphenylcyclohexanol, obtained in 83% yield and
unaltered enantio- and diastereoselectivity. Interestingly, the
monosubstituted complex is unable to promote the formation
of the double addition product: in fact, even using an excess of
phenylboronic acid and high temperature, only 3-phenyl-
cyclohexanone was obtained (entry 4). The use of the atropoi-
someric analogues of 1, i.e. phosphites 1a and 1b containing
respectively R- and S- binaphthyl moieties,16 shows that only
the matched diastereoisomer 1b16 gives rise to a catalytically
active complex, affording R-3-phenylcyclohexanone in 94%
yield and 91% ee (entry 5). This result suggests that, although
the complexation of 1 is non-selective, a high level of asym-
metric induction can be reached because only one of the two
interconverting diastereoisomer affords a catalytically active
complex, and the tropos nature of the complex allows a shift of
the equilibrium between the two diastereoisomeric M and P
forms towards the catalytically active complex. Taking into
account that the prevailing obtained enantiomer is always R-
configured, an M sense of twist for the biphenyl moiety of the
catalytically active complex, corresponding to the S config-
uration, can be inferred.
1 Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai and N. Miyaura,
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10 SEC measurements (polystyrene standard) on the disubstituted
complex confirmed the presence of two species having different
nuclearity: the molecular weight of one species was twice the
molecular weight of the other one (see ESI, Fig. S5w).
11 Large ligands can generate 1 : 1 Rh(I) : L complexes: O. Njyomura,
T. Iwasawa, N. Sawada, M. Tokunaga, Y. Obora and Y. Tsuji,
Organometallics, 2005, 24, 3468.
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13 Structure B can be excluded on the basis of the position of the
doublet signal in the 31P NMR spectrum, corresponding to
the signal of the monosubstituted complex obtained from
[Rh(acac)(C2H4)2].
In summary tropos phosphite 1 shows a unique behavior in
its coordination to [{RhCl(C2H4)2}2] giving rise to mono- or
disubstituted complexes depending on the P/Rh ratio and
the reaction time. This tunable coordination permits fine
tuning of the asymmetric addition of phenylboronic acid to
14 A very similar behavior is observed for the disubstituted complexes
(see ESI, Fig. S2w), although the complexity of the spectrum
prevents complete assignment of the signals.
15 K. Vandyck, B. Matthys, M. Willen, K. Robeyns, L. Van Meervelt
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16 A. Iuliano and P. Scafato, Tetrahedron: Asymmetry, 2003, 14, 611.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 457–459 | 459