Enantioselectivity increases with reactivity: Electronically controlled asymmetric addition of diethylzinc to aromatic aldehydes catalyzed by a chiral pyridylphenol

Full text of DOI:10.1021/jo9609889

8
002
J . Org. Chem. 1996, 61, 8002-8003
En a n tioselectivity In cr ea ses w ith
Rea ctivity: Electr on ica lly Con tr olled
Asym m etr ic Ad d ition of Dieth ylzin c to
Ar om a tic Ald eh yd es Ca ta lyzed by a Ch ir a l
P yr id ylp h en ol
Sch em e 1. Syn th esis a n d Resolu tion of Ch ir a l
P yr id ylp h en ol 4
Huichang Zhang, Feng Xue, T. C. W. Mak, and
Kin Shing Chan*
Department of Chemistry, The Chinese University of Hong
Kong, Shatin, New Territories, Hong Kong
Received May 29, 1996 (Revised Manuscript Received
September 17, 1996)
Achieving enantioselective reactions through a cata-
lytic process is recognized as one of the most important
and challenging problems in organic synthesis, and
therefore it has received much attention. Enormous
progress has been made in this area during the past
decade.1 However, the factors governing enantioselec-
tivity remain the subject of speculation even in reactions
that have been extensively studied.2 Enantioselectivity
in catalytic asymmetric reaction is usually interpreted
in steric terms.3 Electronic effects have seldom been
reported to control enantioselectivity even though the
electronic properties of both the catalyst and substrate
can have profound effects in fundamental organometallic
NaOH,�
aq MeOH
60 °C, 24 h
sulfonates 5.9 Chromatographic separation of on silica
gel and subsequent alkaline hydrolysis finally yielded the
processes.4
,5
6
In the limited number of studies of elec-
1
0
enantiomerically pure ligands (R)-(+)-4 and (S)-(-)-4
Scheme 1).
The results of the enantioselective catalytic addition
of diethylzinc to aromatic aldehydes (eq 1) by (R)-(+)-(4)
are summarized in Table 1. The reactions were con-
ducted at 0 °C in toluene in the presence of 5 mol % of
R)-(+)-4 (optical purity > 99.5%) under nitrogen for 48
h with 2 equiv of Et Zn to give high yields of alcohols
a -e with moderate to high enantioselectivity.
tronic effects, the underlying reasons are poorly under-
stood. Our interest in asymmetric catalysis has prompted
us to design and synthesize the new biaryl chiral N,O-
ligand 4. In the catalytic enantioselective addition of
diethylzinc to p-substituted benzaldehydes catalyzed by
this chiral pyridylphenol (R)-(+)-4, we have observed for
the first time that the enantioselectivity (1) depends on
the electronic nature of the aryl aldehydes in a linear free
energy relationship and (2) increases with more reactive
substrates.
(
(
2
1
0-12
7
The chiral pyridylphenol 4 was synthesized from
2
-bromo-3,5-di-tert-butylanisole through the Suzuki cross
7
coupling of boronic acid 1 with 2-bromo-3-methyl-
pyridine (2) in the presence of 2.0 equiv of KO Bu and 5
mol % of Pd(Ph
t
8
3
P)
4
in DME to produce 3, which was then
treated with pyridine hydrochloride to afford recemic 4
Most remarkably, the enantioselectivity of the reac-
tions is subjected to a remote electronic effect; the
(Scheme 1).
Resolution of this pyridylphenol was carried out with
S)-(+)-camphorsulfonyl chloride via the diastereomeric
(
(9) The R and S configurations of 4 were determined by X-ray
analysis of (S,S)-5, which after alkaline hydrolysis afforded (S)-(-)-
1
0
(
1) For recent reviews, see: (a) Kotha, S. Tetrahedron 1994, 50,
1 1 1
4. X-ray structure analysis of (S,S)-(+)-5: P2 2 2 ; a ) 11.284(2) Å,
3
3
639. (b) Noyori, R. Ibid. 1994, 50, 4259. (c) Nugent, W. A.; RajanBabu,
b ) 12.846(2) Å, c ) 19.739(2) Å, V ) 2861.2(10) Å , Z ) 4, Fcalc )
3
T. V.; Burk, M. J . Science 1993, 259, 479. (d) Soai, K.; Niwa, S. Chem.
Rev. 1992, 92, 833. (e) Noyori, R.; Tokunaga, M.; Kitamura, M. Bull.
Chem. Soc. J pn. 1995, 68, 36. (f) Shibata, T.; Mirioka, M.; Hayase, T.;
Choji, K.; Soai, K. J . Am. Chem. Soc. 1996, 118, 471.
1.188 g cm- ; Mo KR radiation (graphite monochromator); scan range
3° e 2θ e 50°; total number of reflections 2850, observed reflections
o w
1786 (F > 4.0σ (F)), R ) 0.0491, R ) 0.0506; GOF ) 1.17. Siemens
P4 four-circle X-ray diffractometer, data calculated with SHELXTL-
2
7
(2) (a) Giovannetti, J . S.; Kelly, C. M.; Landis, C. R. J . Am. Chem.
PC on a PC486. (R)-(+)-4: [θ]251 ) -5940°, ∆ꢀ251 ) -1.80, [R]
24.6 (c ) 0.35, CHCl ), optical purity > 99.5% (chiral Daicel OD HPLC
colomn, t ) 18.6 min, flow rate 0.3 mL/min, hexane/2-propanol ) 4:1).
(S)-(-)-4: [θ]251 ) +5346°, ∆ꢀ251 ) +1.62, [R]
CHCl ), optical purity >96% (chiral Daicel OD HPLC colomn, t
D
) +
Soc. 1993, 115, 4040. (b) Noyori, R.; Kitamura, M. Angew. Chem., Int.
Ed. Engl. 1991, 30, 49.
(
b) J . Bao, Wulff, W. D.; Rheingold, A. L. Ibid. 1993, 115, 3814.
(
3
R
2
7
3) (a) Corey, E. J .; Noe, M. C. J . Am. Chem. Soc. 1993, 115, 12579.
D
) -24.8 (c ) 0.35,
) 13.0
(
3
R
4) Farina, V.; Krishnan, B. J . Am. Chem. Soc. 1993, 115, 9585.
5) Mendez, N. Q.; Seyler, J . W.; Arif, A. M.; Gladysz, J . A. J . Am.
min, flow rate 0.3 mL/min, hexane/2-propanol ) 4:1). The author has
deposited atomic coordinates for this structure with the Cambridge
Crystallographic Data Centre. The coordinates can be obtained, on
request, from the Director, Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge, CB2 1EZ, UK.
(
Chem. Soc. 1993, 115, 2323.
6) (a) Schnyder, A.; Hintermann, L.; Togni, A. Angew. Chem., Int.
(
Ed. Engl. 1995, 34, 931. (b) RajanBabu, T. V.; Ayers, T. A.; Casalnuovo,
A. L. J . Am. Chem. Soc. 1994, 116, 4101. (c) Nishiyama, H.; Yamaguchi,
S.; Kondo, M.; Itoh, K. J . Org. Chem. 1992, 57, 4306. (d) J acobsen, E.
N.; Zhang, W.; Guler, M. L. J . Am. Chem. Soc. 1991, 113, 6703. (e)
Park, S.-B. Murata, K.; Matsumoto, H. Nishiyama, H. Tetrahedron:
Asymmetry 1995, 6, 2487. (f) Corey, E. J .; Helal, C. J . Tetrahedron
Lett. 1995, 36, 9153.
(10) (a) IUPAC Tentative Rule for the Nomenclature of Organic
Chemistry: J . Org. Chem. 1970, 35, 2849.
(11) Noryori, R.; Suga, S.; Kawai, K.; Okada, S.; Kitamura, M.;
Oguni, N.; Hayashi, M.; Kaneko, T.; Matsuda, Y. J . Organomet. Chem.
1990, 382, 19.
(12) Trost, N. M.; Belletire, J . L.; Godleski, S.; McDougal. P. G.;
Balkovec, J . M.; Baldwin, Ghristy, M. E.; Ponticello, G. S.; Varga, S.
L.; Springler, J . P. J . Org. Chem. 1986, 51, 2370.
(
(
7) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2497.
8) Zhang, H.; Chan, K. S. Tetrahedron Lett. 1996, 37, 1043.
S0022-3263(96)00988-7 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 23, 1996 8003
Ta ble 1. En a n tioselective Ad d ition of Dieth ylzin c to
Ar om a tic Ald eh yd es Ca ta lyzed by Ch ir a l P yr id ylp h en ol
(
S)-(+)-4
product
X
% yield
% eea
confignb
7
7
7
7
7
a
b
c
d
e
NMe2
OMe
H
Cl
CN
88
96
92
97
92
40
66
75
80
89
Rc
R
R
d
R
R
d
a
Determined by chiral Daicel OD HPLC column. b Absolute
configurations determined by comparison of reported optical
1
1 c
rotations.
Absolute configurations determined by comparsion
d
of the same sign as the R isomer of 7b-d . Absolute configura-
tions determined by H NMR of its ester of (S)-O-methylmandelic
1
1
2
acid.
F igu r e 1. Plote of the optical yields of alcohols vs Hammett
constant σ .
p
substrates bearing electron-withdrawing groups in the
para-positions of aryl aldehydes afforded higher enantio-
selectivity than those with electron-donating groups.
lower both at 25 and -23 °C (ee < 1 and 35%, respec-
tively), and an inversion temperature likely fell at around
0 °C.16 Diasteromeric binding of aldehydes to zinc
leading to more reactive and less stable intermediates
for electron-deficient aldehydes might be possible to
account the electronic influence in a manner similiar to
that proposed by Halpern for the mechanism of asym-
metric hydrogenation.17
1
3
From the Hammett plot of log (R/S) versus Hammett
1
4
2
constants σ
.99 (Figure 1). The enantioselectivity of 7e is 89% ee
but that for 7c is only 75% ee, for example; this corre-
p
,
a straight line was obtained with R )
0
-
1
sponds to a difference of more than 0.5 kcal mol in
∆G for the two reactions.
q
∆
The enantioselectivity remarkably increases with more
In summary, the novel chiral pyridylphenol (R)-(+)-4
has been shown to catalyze the addition of diethylzinc
to aromatic aldehydes with moderate to high enantio-
selectivity. Most importantly, this enantioselectivity fol-
lows a linear free energy relationship with higher enan-
tioselectivity obtained for more reactive aryl aldehydes.
Further modification of ligands, applications in asym-
metric catalysis, and theoretical calculations are in
progress.
reactive substrates. By competiton experiments, the
relative reactivities of the p-arylaldehydes were found to
be CN (4.8), Cl (3.4), H (1.0), and Me N (0.1). This
2
reactivity pattern parallels the enantioselectivity. To the
best of our knowledge, only one other report has men-
tioned this phenomenon.6
e
The origin of these remarkable electronic influences
on the enantioselectivity remains unclear. The mecha-
nism of diethylzinc addition to aldehydes catalyzed by
amino alcohols has been eluciated to involve dinuclear
zinc species.15 The enantioselectivity was observed to be
Ack n ow led gm en t. We thank the Reseach Grants
Council of Hong Kong (CUHK 22/91) for financial
support.
q
(
13) The term ln (R/S) is proportional to -∆∆G according to the
Su p p or tin g In for m a tion Ava ila ble: 1H and 1C NMR
data and spectra for 4, 5, and 7 and experimental procedures
following equation:
q
log (R/S) ) -∆∆G /RT
(8 pages).
q
Here, -∆∆G is the free energy difference between two dia-
J O9609889
stereomeric transition states leading to enantiomeric products.
(
14) Gordon, A. J .; Ford, R. A. The Chemist's Companion; J ohn
Wiley: New York, 1972.
15) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J . Am. Chem.
Soc. 1989, 111, 4028.
(16) Buschmann, H.; Scharf, H.-D.; Hoffman, N.; Esser, P. Angew.
Chem., Int. Ed. Engl. 1991, 30, 477.
(17) Landis, C.; Halpern, J . J . Am. Chem. Soc. 1987, 109, 1746.
(