Communications
and then filtered. The filtrate was extracted with diethyl ether (3
15 mL) and the combined organics were dried (anhydrous Na2SO4),
filtered, and concentrated. Chromatography on silica (10% 1:9
EtOAc/Hex) gives 1-(2-methoxyphenyl)ethanol (3a, 194 mg, 98%)
as a clear oil: capillary GC analysis (J&W Scientific 30 m 0.25 mm
ID Cyclosil b, 1208C (1 min hold) to 1308 at 18minÀ1 then to 1658 at
28minÀ1) found peaks at 21.19 (97.2%, (R)-3a) and 23.55 (2.8%, (S)-
chiral phosphite moiety present in each SAL, as well as the
best results previously reported for each substrate. For
substrates 2a (R = OMe) and 2c–e (R = CF3, Cl, F), the
SAL identified is the most selective catalyst reported to date.
For 2b (R = Me), the best SAL and literature results are
nearly equivalent.
The importance ofthe heterodimeric zinc complex as a
structural element for the SALs is further illustrated by
comparing three diastereomeric ligands derived from (S,S)-
and (R,R)-1E. Even though the ligating groups and tethers
are identical in all three zinc complexes, the results obtained
in the hydroboration of2-methylstyrene ( 2b) vary signifi-
cantly. In contrast to the (SS,RR)-heterodimer, SAL EE
(91% ee, 95% a-3b), the diastereomeric (SS,SS)- and
(RR,RR)-homodimers, that is, [{(S,S)-1E}2Zn] and [{(R,R)-
1E}2Zn], exhibit low reactivity and lower selectivity: 87% ee
(84% a-3b) and 79% ee (82% a-3b), respectively.
In summary, a series ofTADDOL phosphite-bearing
SALs, readily prepared in combinatorial arrays by chirality-
directed self-assembly, provides a focused ligand library for
RhI-catalyzed hydroboration. These SALs exhibit the unique
feature of achieving high enantioselectivity through the subtle
manipulation ofthe chiral catalytic pocket by small system-
atic changes in the ligand scaffold, an approach not available
with classic ligand designs. The ligands differ only in scaffold
structure, yet the enantioselectivity obtained in catalytic
asymmetric hydroboration of2-methoxystyrene varies rfom
96% ee favoring the R-configuration to 30% ee favoring S.
{RhICl} and {RhIBF4} catalyst precursors and different sub-
strates require different ligand scaffolds to achieve success.
Nevertheless, {(SAL XY)RhI} catalysts afford high regiose-
lectivity (92–99% a3) and enantioselectivity (91–96% ee)
across a series of ortho-substituted styrenes varying in
electronic character and steric demand. Thus, a facile
method of self-assembly is exploited to fine tune catalysts
by ligand scaffold optimization, improving substrate general-
ity in a reaction that has thus far exhibited rather limited
substrate scope. Studies directed toward understanding the
structural basis for the wide variation in selectivity as a
function of ligand scaffold (i.e. the structure–activity relation-
ship ofthese ligands) are in progress.
1
3a); H NMR (400 MHz, CDCl3): d = 7.39 (1H, dd, J = 7.5, 1.4 Hz),
7.37–7.26 (1H, dt, J = 8.2, 1.6 Hz), 7.00 (1H, t, J = 7.5 Hz), 6.90 (1H,
d, J = 8.2 Hz), 5.15–5.11 (1H, q, J = 13.0, 6.5 Hz), 3.88 (3H, s)
1.53 ppm (3H, d, J = 6.5 Hz); 13C NMR (100 MHz, CDCl3): d = 156.5,
133.6, 128.2, 126.1, 120.8, 110.4, 66.4, 55.3, 23.0 ppm; [a]2D5 = + 25.88
(c = 1.4 g(100mL)À1, CHCl3).
Received: July 13, 2007
Revised: September 13, 2007
Published online: December 21, 2007
Keywords: asymmetric synthesis · combinatorial chemistry ·
.
hydroboration · self-assembly · stereoselective catalysis
[2] Recent reviews: a) A.-M. Carroll, T. P. OꢀSullivan, P. J. Guiry,
[3] a) S. A. Moteki, D. Wu, K. L. Chandra, D. S. Reddy, J. M.
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46, 930 – 933; e) M. Kuil, P. E. Goudriaan, P. W. N. M. Van Leeu-
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Experimental Section
[(SAL HC)Rh(nbd)BF4]-catalyzed asymmetric hydroboration of2-
methoxystyrene:
A solution of[{( S,S)-1H}2Zn] (10.0 mg, 1.4
10À2 mmol) and [{(R,R)-1C}2Zn] (10.0 mg, 1.4 10À2 mmol) in
CH2Cl2 (10 mL) was stirred at ambient temperature (10 min), and
then a solution of[Rh(nbd) 2BF4] (9.7 mg, 2.6 10À2 mmol) in CH2Cl2
(5 mL) was added. The resulting mixture was stirred at ambient
temperature (0.5 h), after which the volatile solvent was removed
under vacuum. The residue was dissolved in DME (10 mL), stirred
(0.5 h), and then a solution of2-methoxystyrene ( 2a, 174.0 mg,
1.30 mmol) in DME (2.0 mL) and powdered 4- molecular sieves (ca.
0.5 g) were added. The resulting mixture was cooled (08C) and a
solution ofpinacolborane (199.0 mg, 1.56 mmol) in DME (4.0 mL)
added dropwise. The reaction mixture was gradually warmed to room
temperature and stirred (12 h). Afterwards, the mixture was again
cooled (08C) and quenched by the addition ofMeOH (10 mL),
NaOH(aq) (3.0m, 15 mL), and H2O2(aq) (1 mL ofa 30% solution).
The ice bath was removed, and the resulting mixture stirred (3 h, RT)
896
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Angew. Chem. Int. Ed. 2008, 47, 894 –897