Asymmetric Kharasch Reaction: Catalytic Enantioselective Allylic Oxidation of Olefins Using Chiral Pyridine Bis(diphenyloxazoline) - Copper Complexes and tert-Butyl Perbenzoate

Article abstract of DOI:10.1021/jo972132p

Copper complexes of chiral pyridine bis(diphenyloxazoline)-type ligands have been studied as catalysts for the enantioselective allylic oxidation of olefins. Using 2.5-5 mol % of these chiral catalysts and tert-butyl perbenzoate as oxidant, optically active allylic benzoates were obtained in up to 86% ee. A variety of copper salts was studied under different conditions and in different solvents. Acetone was found to be a superior solvent for the reaction. Use of phenylhydrazine in conjunction with the chiral copper complex played a crucial role in increasing the rate of the reaction. Use of 4 ? molecular sieves increased the optical yield of product in almost every case.

Full text of DOI:10.1021/jo972132p

J . Org. Chem. 1998, 63, 2961-2967
2961
Asym m etr ic Kh a r a sch Rea ction : Ca ta lytic En a n tioselective Allylic
Oxid a tion of Olefin s Usin g Ch ir a l P yr id in e
Bis(d ip h en yloxa zolin e)-Cop p er Com p lexes a n d ter t-Bu tyl
P er ben zoa te†,‡
Govindasamy Sekar, Arpita DattaGupta, and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
Received November 20, 1997
Copper complexes of chiral pyridine bis(diphenyloxazoline)-type ligands have been studied as
catalysts for the enantioselective allylic oxidation of olefins. Using 2.5-5 mol % of these chiral
catalysts and tert-butyl perbenzoate as oxidant, optically active allylic benzoates were obtained in
up to 86% ee. A variety of copper salts was studied under different conditions and in different
solvents. Acetone was found to be a superior solvent for the reaction. Use of phenylhydrazine in
conjunction with the chiral copper complex played a crucial role in increasing the rate of the reaction.
Use of 4 Å molecular sieves increased the optical yield of product in almost every case.
Sch em e 1
In tr od u ction
The allylic oxidation of olefins with peresters in the
presence of copper salts to give allylic esters has been
previously studied by Kharasch and co-workers.1 The
reaction exploits the special nature of an allylic CH bond
and proceeds in a regioselective manner. For example,
in case of an acyclic terminal olefin, a mixture of internal
secondary ester and a primary ester is formed in which
the former one predominates (Scheme 1). Since the
allylic ester can easily be converted into allylic alcohol
by saponification or reduction method, the Kharasch
reaction eventually becomes an allylic alcohol synthesis.
Asymmetric version of this reaction will nicely comple-
ment other methods to prepare chiral allylic alcohols,
which are useful building blocks in organic synthesis.2,3
Early attempts for asymmetric version of this reaction
using copper complexes of (+)-R-ethyl camphorate,4a
chiral Schiff bases,4b and optically active amino acids4b
gave a very poor asymmetric induction (5-17% ee) in the
allylic oxidation of olefins. The area was dormant for a
number of years until 1991, when Muzart studied allylic
oxidation of cyclohexene with copper complexes of L-
amino acids using acetic acid and t-BuOOH, but the
asymmetric induction still remained poor (<30% ee).5a
A few years later, Muzart and Levina5b,c and Feringa et
al.6 independently studied the same reaction with cop-
per(I) and -(II) complexes of a variety of optically active
amino acids. Under their best conditions using a Cu(II)
complex of (S)-proline, cyclopentene and cyclohexene gave
54% and 63% ee’s, respectively. During the course of our
study on enantioselective allylic oxidation of olefins,
important contributions were made by several groups.7,8
Pfaltz et al.8a and Andrus et al.8b,c independentely re-
ported that chiral copper(I)-bis(oxazoline) complexes
would catalyze the allylic oxidation of olefins in a
reasonably good enantioselective manner. Around the
same time, Katsuki et al.8d,e introduced copper(II) com-
plexes of tris(oxazoline) ligand that showed some im-
provement in the enantioselective allylic oxidation of
cyclopentene; but, however, other olefins gave only mod-
est enantioselectivity. Andersson et al.8f used a chiral
copper complex of a bicyclic amino acid for the same
reaction, but the enantioselectivity remained modest. The
universal problem with all the previous reports had been
† Dedicated to Professor E. J . Corey on the occasion of his 70th
birthday.
‡ Part of the work was presented in the form of an invited lecture
at the 48th ACS Southeast Regional Meeting on asymmetric synthesis
Nov 10-13, 1996, Greenville, SC.
(1) (a) Kharasch, M. S.; Sosnovsky, G. J . Am. Chem. Soc. 1958, 80,
756. (b) Kharasch, M. S.; Sosnovsky, G.; Yang, N. C. J . Am. Chem.
Soc. 1959, 81, 5819. (c) For a review on the Kharasch reaction, see:
Rawlinson, D. J .; Sosnovsky, G. Synthesis 1972, 1.
(2) For general reviews on the use of chiral allylic alcohols in organic
synthesis, see: (a) Wipf, P. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 5, p 827. (b) J ohnson,
R. A.; Sharpless, K. B. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon Press: Oxford, 1991; Vol. 7, p 389. (c) Godleski, S.
A. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: Oxford, 1991; Vol. 4, p 585. (d) Lipshutz, B. H.; Sengupta, S.
In Organic Reactions; Wiley: New York, 1992; Vol. 41, p 135. (e)
Kazmaier, U. Liebigs Ann./ Recl. 1997, 285.
(3) For some recent references on application of chiral allylic alcohols
in synthesis, see: (a) Charette, A. B.; Lemay, J . Angew. Chem., Int.
Ed. Engl. 1997, 36, 1090 and references cited therein. (b) Marino, J .
P.; Viso, A.; Lee, J .-D.; Fernandez, de la P. R.; Fernandez, P.; Rubio,
M. B. J . Org. Chem. 1997, 62, 645. (c) Adam, W.; Corma, A.; Reddy, T.
I.; Renz, M. J . Org. Chem. 1997, 62, 3631. (d) Ukaji, Y.; Taniguchi, K.
Sada, K.; Inomata, K. Chem. Lett. 1997, 547.
(4) (a) Denney, D. B.; Napier, R.; Cammarata, A. J . Org. Chem. 1965,
30, 3151. (b) Araki, M.; Nagase, T. Ger. Offen. 2625030, 1976; Chem.
Abstr. 1977, 86, 120886r.
(5) (a) Muzart, J . J . Mol. Catal. 1991, 64, 381. (b) Levina, A.; Muzart,
J . Tetrahedron: Asymmetry 1995, 6, 147. (c) Levina, A.; Muzart, J .
Synth. Commun. 1995, 25, 1789. (d) Levina, A.; Francoise, H.; Muzart,
J . J . Organomet. Chem. 1995, 494, 165.
(6) (a) Rispens, M. T.; Zondervan, C.; Feringa, B. L. Tetrahedron:
Asymmetry 1995, 6, 661. (b) Rispens, M. T.; Zondervan, C.; Feringa,
B. L. Tetrahedron: Asymmetry 1996, 7, 1895.
(7) DattaGupta, A.; Singh, V. K. Tetrahedron Lett. 1996, 37, 2633.
(8) (a) Gokhale, A. S.; Minidis, A. B. E.; Pfaltz, A. Tetrahedron Lett.
1995, 36, 1831. (b) Andrus, M. B.; Argade, A. B.; Chen, X.; Pamment,
M. G. Tetrahedron Lett. 1995, 36, 2945. (c) Andrus, M. B.; Chen, X.
Tetrahedron 1997, 53, 16229. (d) Kawasaki, K.; Tsumura, S.; Katsuki,
T. Synlett 1995, 1245. (e) Kawasaki, K.; Katsuki, T. Tetrahedron 1997,
53, 6337. (f) Sodergren, M. J .; Andersson, P. G.; Tetrahedron Lett. 1996,
37, 7577.
S0022-3263(97)02132-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/01/1998

2962 J . Org. Chem., Vol. 63, No. 9, 1998
Sekar et al.
Sch em e 2
the very slow rate of the reaction, requiring several days
for completion, and sometimes close to a month. Besides
this, optical and chemical yield for some cycloolefins had
been very poor. In this paper, we address some of these
issues and delineate full details of our work in this area.
Resu lts a n d Discu ssion
Design, synthesis, and tuning of a suitable chiral
ligand around a metal center is an important task in
asymmetric synthesis.9 During the past several years,
we were involved in designing chiral bases for conversion
of epoxides to chiral allylic alcohols.10 We now report that
the same goal of preparing chiral allylic alcohols can be
achieved by an enantioselevtive allylic oxidation of olefins
using a catalytic amount of copper complex of chiral
pyridine bis(diphenyloxazoline) ligand (henceforth we will
call it “pybox-diph” ligand). Pyridine bis(oxazoline)type
ligand (pybox ligand) was first used by Nishiyama for
asymmetric hydrosilylation reactions.11 Later on, these
ligands were used for asymmetric dehydrogenative sily-
lation of ketones,12 chiral recognition of binaphthol,13
enantioselective cyclopropanation reactions,14 aldol reac-
tions,15 and Diels-Alder reactions.16 While working on
an asymmetric cyclopropanation reaction17 using an ip-
pybox-diph ligand 4a , we envisioned that its copper
complex would be quite suitable as a catalyst for the
enantioselective allylic oxidation of olefins with a per-
ester. To carry out the reactions, a variety of pybox-
diph ligands were synthesized. The ligands 4a -d were
synthesized in two steps, viz., by coupling of 2,6-dipiconyl
chloride 118 and (S)-diphenylamino alcohol 219 followed
by intramolecular condensation of 3 with methane-
sulfonic acid (Scheme 2).17,20 Similarly, the ligand 7 was
synthesized from isophthalyl chloride 5 (Scheme 3).21
In our initial study, the complex of 4a 17 with CuI in
acetonitrile was found to catalyze the allylic oxidation of
Sch em e 3
Ta ble 1. Effect of Cop p er Sa lt in th e Com p lex w ith th e
Liga n d 4a on Ca ta lytic En a n tioselective Allylic
Oxid a tion of Cycloh exen ea
(9) Noyori, R. Asymmetric Catalysis in Organic synthesis; Wiley:
New York, 1994.
(10) (a) Bhuniya, D.; DattaGupta, A.; Singh, V. K. J . Org. Chem.
1996, 61, 6108. (b) Bhuniya, D.; DattaGupta, A.; Singh, V. K.
Tetrahedron Lett. 1995, 36, 2847. (c) Bhuniya, D.; Singh, V. K. Synth.
Commun. 1994, 24, 375. (d) Saravanan, P.; Singh, V. K. Tetrahedron
Lett. 1998, 39, 167.
(11) (a) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846. (b) Nishiyama, H.;
Kondo, M.; Nakamura, T.; Itoh, K. Organometallics 1991, 10, 500. (c)
Nishiyama, H.; Yamaguchi, S.; Kondo, M.; Itoh, K. J . Org. Chem. 1992,
57, 4306.
(12) Nagashimha, H.; Ueda, T.; Nishiyama, H.; Itoh, K. Chem. Lett.
1993, 347.
entry
Cu salt
CuI
CuCN
Cu(OTf)2
solvent
timec
% yieldd
% eee
1
2
3
4
5
MeCN
MeCN
acetone
acetone
acetone
05 d
05 d
28 h
06 d
24 h
37
48
44
87
65
09
42
26
73
71
(CuOTf)2PhH
[Cu(I)OTf]f
a
The reaction was done at rt, which here refers to 30 °C.
bPhCOOH and t-BuOOH were used for entries 1 and 2. PhCO3-
t-Bu was used for entries 3-5. c h for hours and d for days.
Isolated yield. e Determined by HPLC on chiral columns. f Pre-
d
pared in situ by reducing the Cu(II) OTf complex with PhNHNH2.
(13) Nishiyama, H.; Tajima, T.; Takayama, M.; Itoh, K. Tetrahe-
dron: Asymmetry 1993, 4, 1461.
cyclohexene with tert-butyl hydroperoxide and benzoic
acid, but the enantioselectivity was very poor (Table 1,
entry 1). We then tried other copper complexes prepared
from various copper salts such as CuCN, Cu(II) triflate,
and Cu(I) triflate. It was found out that all of them
catalyzed the allylic oxidation reaction, but only the 4a -
Cu(I) triflate complex gave reasonably higher asymmetric
induction. It was observed that the rate of the reaction
depended upon how the 4a -Cu(I) triflate complex was
prepared and used in the reaction (Table 1, entry 4 vs
5). The 4a -Cu(I) triflate complex was prepared in two
ways. In the first way, the ligand 4a was directly treated
with (CuOTf)2‚PhH, which is available commercially
(Table 1, entry 4). In the second way, the Cu(I) species
was prepared in situ by reducing the complex 4a -Cu-
(OTf)2 with phenylhydrazine (Table 1, entry 5).22 With
4a -Cu(I) triflate complex prepared in situ by using
(14) (a) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh,
K. J . Am. Chem. Soc. 1994, 116, 2223. (b) Doyle, M. P.; Peterson, C.
S.; Zhou, Q.-L.; Nishiyama, H. Chem. Commun. 1997, 951.
(15) (a) Evans, D. A.; Murry, J . A.; Kozowski, M. C. J . Am. Chem.
Soc. 1996, 118, 5814. (b) Evans, D. A.; MacMillan, D. W. C.; Campos,
K. R. J . Am. Chem. Soc. 1997, 119, 10859.
(16) (a) Evans, D. A.; Murry, J . A.; von Matt, P.; Norcross, R. D.;
Miller, S. J . Angew. Chem., Int. Ed. Engl. 1995, 34, 798. (b) Davies, I.
W.; Gerena, L.; Cai, D.; Larsen, R. D.; Verhoeven, T. R.; Reider, P. J .
Tetrahedron Lett. 1997, 38, 1145.
(17) DattaGupta, A.; Bhuniya, D.; Singh, V. K. Tetrahedron 1994,
50, 13725.
(18) Newcomb, M.; Tinko, J . M.; Walba, D. M.; Cram, D. J . J . Am.
Chem. Soc. 1977, 99, 6392.
(19) Gupta, A. D.; Singh, B.; Singh, V. K. Ind. J . Chem. 1994, 33B,
981.
(20) For the similar cyclization using BF3‚Et2O, see: Davies, I. W.;
Gerena, L.; Lu, N.; Larsen, R. D.; Reider, P. J . J . Org. Chem. 1996,
61, 9629.
(21) A similar type of ligand without having diphenyl groups has
been synthesized previously. For reference, see: Bolm, C.; Weickhardt,
K.; Zehnder, M.; Ranff, T. Chem. Ber. 1991, 124, 1173.

Asymmetric Kharasch Reaction
J . Org. Chem., Vol. 63, No. 9, 1998 2963
Ta ble 2. Effect of P h en ylh yd r a zin e a n d 4 Å Molecu la r
Sieves on Ca ta lytic En a n tioselective Allylic Oxid a tion of
Cycloh exen e w ith Ch ir a l 4a -(Cu OTf) Com p lexa
Ta ble 3. Effect of P h en ylh yd r a zin e on Ca ta lytic
En a n tioselective Allylic Oxid a tion of Olefin s w ith Ch ir a l
4a -(Cu OTf) Com p lexa
entry
PhNHNH2
4 Å
timeb
% yieldc
% eed
1
2
3
4
no
yes
no
No
No
Yes
Yes
06 d
05 h
21 d
10 h
87
78
88
77
73
70
86
67
yes
a
The reaction was done at rt, which here refers to 18-20 °C.
b h for hour and d for days. c Isolated yield. Determined by HPLC
d
on Chiracel OJ and OD-H columns.
PhNHNH2, the rate of the reaction was fast and it took
much less time (6 days vs 1 day) without affecting the
enantioselectivity to a great extent (73% ee vs 71% ee).
With this exciting result, it was imperative to know the
effect of phenylhydrazine on the enantioselective oxida-
tion reaction with a complex prepared from 4a and
commercially available Cu(I) triflate. It was also thought
that if the last traces of moisture from the reaction
mixture was removed by using 4 Å molecular sieves, the
catalytic activity of the copper complex might go up, and
in turn, it might increase the enantioselectivity of the
reaction. So, the effect of PhNHNH2 and 4 Å molecular
sieves was examined on the allylic oxidation of cyclohex-
ene with chiral 4a -(CuOTf) complex in acetone (Table 2).
It was gratifying to note that phenylhydrazine increased
the rate of the reaction severalfold without affecting the
enantioselectivity too much. For example, when cyclo-
hexene was treated with tert-butyl perbenzoate and 5 mol
% of the complex 4a -(CuOTf) in the presence of phenyl-
hydrazine, the reaction time was reduced from 6 days to
5 h (Table 2, entry 1 vs 2). If phenylhydarzine was
replaced by 4 Å molecular sieves, the reaction became
very sluggish. However, the enantioselectivity increased
to 86% (Table 2, entry 3). For cyclohexene, this was the
highest enantioselectivity obtained, to date, for this kind
of transformation. The presence of phenylhydrazine and
4 Å molecular sieves together with the complex in the
reaction mixture was not benificial for asymmetric induc-
tion.
a
The reaction was done at rt, which here refers to 18-20 °C.
h for hours and d for days. c Isolated yield. Determined by
HPLC on chiral columns and by 400 MHz H NMR spectrum of a
Mosher ester of the corresponding alochol.
b
d
1
Ta ble 4. Ca ta lytic En a n tioselective Allylic Oxid a tion of
Olefin s w ith Ch ir a l 4a -(Cu OTf) Com p lex in th e P r esen ce
of 4 Å Molecu la r Sievesa
The drastic effect of phenylhydrazine on the rate of the
reaction in the allylic oxidation of cyclohexene prompted
us to examine its effect on other substrates. We extended
the reaction to several cycloolefins and found out the
similar effects (Table 3). In every case, the reaction time
was reduced from several days to few hours. Besides
this, the enantioselectivity was also high.
Since we had achieved the highest asymmetric induc-
tion (86% ee) in the allylic oxidation of cyclohexene with
the complex 4a -(CuOTf) in the presence of 4 Å molecular
sieves, we subjected other olefins to this condition, and
it was found out that the reaction was very slow in all
the cases (Table 4). Unlike cyclohexene, other olefins did
not give high asymmetric induction in the allylic oxida-
tion reaction.
a
The reaction was done at rt, which here refers to 18-20 °C.
d for days. c Isolated yield. Determined by HPLC on chiral
b
d
columbs and by 400 MHz 1H NMR spectrum of a Mosher ester of
the corresponding alcohol.
It was clear from the Table 3 that the use of phenyl-
hydrazine was highly benificial for the enantioselective
allylic oxidation of olefins with a complex 4a -(CuOTf).
In view of the high cost and handling problem of (CuOTf)
due to its unstability, it was thought to prepare the same
species in situ by reducing a 4a -Cu(OTf)2 complex with
PhNHNH2. Since our initial study on allylic oxidation
of cyclohexene with 4a -Cu(I) triflate prepared in this
manner in acetone was highly encouraging (vide supra),
we examined the effect of other factors such as solvent,
temperature, and additives on the reaction. Solvent
study indicated that acetone and acetonitile were better
than benzene. The rate of the reaction was faster in
acetone in comparison to acetonitile, and the enantiose-
lectivty was comparable (Table 5). Lowering the tem-
perature did improve the enantioselectivity to some
(22) (a) We have confirmed by UV-vis and EPR methods that 4a -
Cu(II) triflate complex gets reduced to Cu(I) species in the presence of
phenylhydrazine. For details, see ref 17. (b) For reduction of Cu(II)
species to Cu(I) with phenylhydrazine, also see: Kosower, E. M. Acc.
Chem. Res. 1971, 4, 193. (c) For use of the same reduction method in
the cyclopropanation reaction, see: Kanemasa, S.; Hamura, S.; Harada,
E.; Yamamoto, H. Tetrahedron Lett. 1994, 35, 7985.

2964 J . Org. Chem., Vol. 63, No. 9, 1998
Sekar et al.
Ta ble 7. En a n tioselective Allylic Oxid a tion of
Ta ble 5. Effect of Solven t a n d 4 Å Molecu la r Sieves on
Ca ta lytic En a n tioselective Allylic Oxid a tion of
Cycloh exen e w ith Ch ir a l 4a -Cu (I) Com p lex Red u ced in
Situ fr om 4a -Cu (OTf)2 by P h en ylh yd r a zin ea
Cycloh exen e w ith Cop p er Com p lexes of Differ en t
Liga n d sa
entry
ligand
timeb
% yieldc
% eed
1
2
3
4
5
4a
4b
4c
4d
7
24 h
24 h
02 d
36 h
24 h
73
79
69
57
62
75
62
23
11
00
entry
solvent
4 Å
timeb
% yieldc
% eed
1
2
3
4
5
6
7
benzene
benzene
acetonitrile
acetonitrile
acetone
no
yes
no
yes
no
yes
yes
24 h
72 h
10 d
15 d
24 h
24 h
30 d
55
70
43
58
65
73
78
28
35
70
80
71
75
79
a
The reaction was done at rt, which here refers to 18-20 °C.
b h for hour and d for days. c Isolated yield. Determined by HPLC
d
acetone
acetone
on chiral columns.
a
All the reactions, except entry 7, was done at rt, which here
Sch em e 4
b
refers to 27-30 °C. The entry 7 was done at 10 °C. h for hours
and d for days. c Isolated yield. Determined by HPLC on chiral
d
columns.
Ta ble 6. Ca ta lytic En a n tioselective Allylic Oxid a tion of
Olefin s w ith Ch ir a l 4a -Cu (I) Com p lex Red u ced in Situ
fr om 4a -Cu (OTf)2 by P h en ylh yd r a zin ea
different ligands under the best conditions we had for
4a . When the isopropyl of the ligand 4a was replaced
by methyl, benzyl, or phenyl, the asymmetric induction
in the allylic oxidation reaction was poor (Table 7). The
absence of any asymmetric induction with ligand 7
indicated that the pyridine N was essential for chirality
transfer in the catalytic allylic oxidation reaction of
olefins.
It was observed that in all the cases (S)-pybox-diph
ligand gave (S)-allylic benzoates. The enantiomeric
excess in the reactions was determined by HPLC on
1
chiral columns and by 400 MHz H NMR spectrum of a
Mosher ester23 of the corresponding allylic alcohol ob-
tained by hydrolysis of benzoates. To see whether there
is any racemization during the hydrolysis of allylic
benzoates, we hydrolyzed 2-cyclohexenyl benzoate 8 (n
) 2) with known optical purity (86% ee, chiralcel OD-H
column) into allylic alcohol 9 (n ) 2), and then converted
back to the benzoate 8 (n ) 2). The analysis of this allylic
benzoate sample by HPLC on a Chiralcel OD-H column
indicated its optical purity to be 85.6% ee. Thus, there
is no racemization during the hydrolysis of allylic ben-
zoates under the reported conditions (Scheme 4).
The mechanism of the Kharasch reaction has been very
well studied. There is enough evidence in the literature
that the reaction proceeds via a radical intermediate. The
Cu(I) species cleaves the perester to give Cu(II) benzoate
10 and tert-butoxy radical.24 The tert-butoxy radical
abstracts an allylic hydrogen to give tert-butyl alcohol and
allylic radical (Scheme 5).25 It has been proposed in the
literature that there are two possibilities for the reaction
of allylic radical with Cu(II) benzoate (Figure 1). The
Cu(II) benzoate may add to the allylic radical to generate
Cu(III) benzoate 11 which can rearrange via a six-
membered cyclic transition state to give allylic benzoate.26
The other possibility could be that there is a bonding
a
The reaction was done at rt, which here refers to 28-30 °C.
h for hour. c Isolated yield. Determined by HPLC on chiral
b
d
columns and by 400 MHz 1H NMR spectrum of a Mosher ester of
the corresponding alochol.
extent, but the longer reaction time discouraged us to
do the reaction at lower temperature (Table 5, entry 7).
Molecular sieves (4 Å) helped to improve the enantiose-
lectivity to some extent in all the solvents. This prompted
us to examine allylic oxidation of other olefins with 4a -
Cu(I) triflate species prepared in situ by phenylhydrazine
in acetone in the presence of 4 Å molecular sieves. The
results are summarized in Table 6. In the case of
cyclopentene, the reaction was complete in just 4 h and
the asymmetric induction was 60%. Cyclohexene and
cycloheptene took 24 h for completion of the reaction, and
the asymmetric induction was 75% and 82%, respectively.
In the case of cyclooctene, the reaction was a bit slow
and it took 3 days for completion. However, the enan-
tioselectivity was 81%. It is worthy of note that the
asymmetric induction obtained in the cases of cyclohep-
tene and cyclooctene is the highest, to date, for the
asymmetric Kharasch reaction.
(23) Dale, J . A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512.
(24) (a) Kochi, J . K. J . Am. Chem. Soc. 1962, 84, 774. (b) Kochi, J .
K.; Bemis, A. Tetrahedron 1968, 24, 5099.
(25) (a) Walling, C.; Zavitsas, A. A. J . Am. Chem. Soc. 1963, 85,
2084. (b) Walling, C.; Thaler, W. J . Am. Chem. Soc. 1961, 83, 3877.
(26) Beckwith, A. L. J .; Zavitas, A. A. J . Am. Chem. Soc. 1986, 108,
8230 and references therein.
Next, to study the effect of different substituents at
the chiral center in the pybox-diph ligand on the allylic
oxidation reaction, we carried out the reactions with

Asymmetric Kharasch Reaction
J . Org. Chem., Vol. 63, No. 9, 1998 2965
Sch em e 5
F igu r e 1.
between an incipient double bond of the allylic radical
and the Cu(II) benzoate as designated in 12.27 In
literature, the former possibility has been favored as the
Cu(III) intermediate has been detected spectroscopi-
cally.26 In view of ours and others finding that Cu(II)
complexes also catalyze the reaction equally well, the
mechanism of the reaction becomes even more compli-
cated. In that case, it can be assumed that the reaction
proceeds via 12, and based on this we propose a transition
state model 13a to account for the obtained asymmetric
induction in the reaction.28 Knowing the complex nature
of redox chemistry of copper, the possibility of an
intermediate of the type 11 can also not be ignored. And
if this is the case, a transition state of the type 13b can
explain the enantioselectivity in the reaction.
In these favorable transition state assemblies, copper
benzoate may attain an orientation to provide a π-stack-
ing of the two aromatic rings.29 Since the distance
between both the rings is approximately 3.5 Å, there
might be some attractive interaction which would stabi-
lize the drawn conformation. In that case, the allylic
radical will approach the Cu species from the less
hindered side as shown in Figure 2. The benzoate oxygen
attacks the allylic carbon, which is electrophilic in nature
due to coordination of incipient double bond with the
copper species. This follows reduction of the Cu species
into its original oxidation state. Thus, the catalytic cycle
of the allylic oxidation of olefins continues.
The reason for the increase in the rate of the reaction
on use of phenylhydrazine is not very clear to us. In a
preliminary study, we observed that phenylhydrazone
increased the rate of the reaction as well. In view of this,
it is proposed that phenylhydrazine reacts with acetone
to form phenylhydrazone, which increases the rate of the
reaction.30 The similar rate enhancement in the allylic
oxidation reaction could not be obtained by replacing it
by amine bases such as pyridine, DBN, or DBU.31 The
role of molecular sieves could be that it removes the last
traces of moisture from the reaction mixture.
F igu r e 2.
near future once it gets wide attention from organic
chemists across the world.
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR spectra were recorded on 60,
300, and 400 MHz spectrometers. Chemical shifts are ex-
pressed in ppm downfield from TMS as internal standard, and
coupling constants are reported in hertz. Routine monitoring
of reactions was performed using silica gel-G obtained from
Acme. All the column chromatographic separations were done
by using silica gel (Acme’s, 60-120 mesh). Petroleum ether
used was of boiling range 60-80 °C. Reactions that needed
anhydrous conditions were run under an atmosphere of dry
nitrogen or argon using flame-dried glassware. The organic
extracts were dried over anhydrous sodium sulfate. Evapora-
tion of solvents was performed at reduced pressure. Tetrahy-
drofuran (THF) was distilled from sodium benzophenone ketyl
under nitrogen. Benzene, dichloromethane, acetonitrile, and
acetone were distilled from CaH2.
Gen er a l P r oced u r e for Syn th esis of Am id o Alcoh ols
(3). To a stirred solution of (S)-diphenylamino alcohol (10
mmol) and Et3N (25 mmol) in CH2Cl2 (30 mL) was added
dropwise a solution of dipicolinyl chloride 1 (5 mmol) in 5 mL
of CH2Cl2 at 0 °C, and the mixture was stirred for 16 h (0 °C
to rt). The reaction mixture was diluted with CH2Cl2 (20 mL)
and washed with aqueous NaHCO3, water, and brine. The
organic layer was dried, and the solvent was evaporated in
vacuo. Purification by column chromatography over silica gel
gave pure coupled product 3.
In conclusion, we have studied enantioselective allylic
oxidation of olefins with a copper complex of pybox-diph
ligands. We have shown for the first time that the rate
of the reaction can be increased severalfold by using
phenylhydrazine. Under the best conditions, we were
able to convert cyclic olefins to (S)-allylic benzoates in
up to 86% ee. Although there is some limitaion32 with
this reaction, the methodology will be highly useful in
N,N′-Bis[1′-(S)-isopr opyl-2′,2′-diph en yl-2′-h ydr oxyeth yl]-
2,6-p yr id in ed ica r boxa m id e (3a ).17 This was prepared as
per our own procedure: yield 90%; mp 110-111 °C; Rf 0.22
(1:4, EtOAc in petroleum ether); [R]25 -46.2° (c 1.0, CHCl3);
D
(27) Kochi, J . K.; Mains, H. E. J . Org. Chem. 1965, 30, 1862.
(28) Professor Muzart is also quite apprehensive about the tradi-
tional mechanism. For details, see ref 5d.
(29) For a review on the π stacking effect in asymmetric synthesis,
see: J ones, G. B.; Chapman, B. J . Synthesis 1995, 475.
(30) We have observed that Cu(II) species can be reduced to Cu(I)
using phenylhydrazone.
(31) For allylic oxidation of olefins using a complex of DBN/DBU-
Cu(OTf)2, see: Sekar, G.; DattaGupta, A.; Singh, V. K. Tetrahedron
Lett. 1996, 37, 8435.
1H NMR (DMSO-d6, 400 MHz) δ 0.83 (d, J ) 6.8 Hz, 6H), 1.08
(d, J ) 6.8 Hz, 6H), 1.81 (m, 2H), 5.02 (d, J ) 11.2 Hz, 2H),
6.06 (s, 2H, OH)), 7.02 (m, 2H), 7.15 (m, 6H), 7.32 (t, J ) 7.2
(32) The drawback of the reaction is that acyclic olefins reacted very
slowly and gave very poor asymmetric induction. For example, 1-octene
gave 11% ee in the allylic oxidation reaction with the ligand 4a under
the best conditions.

2966 J . Org. Chem., Vol. 63, No. 9, 1998
Sekar et al.
Hz, 4H), 7.53 (m, 8H), 8.0 (bs, 2H, NH), 8.06 (dd, J ) 8.0, 6.0
Hz, 1H), 8.26 (d, J ) 10.8 Hz, 2H).
m/z) 674 (M+ + 1). Anal. Calcd for C47H35N3O2: C, 83.78; H,
5.24; N, 6.24. Found: C, 83.52; H, 5.12; N, 6.11.
N,N′-Bis[1′-(S)-isopr opyl-2′,2′-diph en yl-2′-h ydr oxyeth yl]-
1,3-ben zen ed ica r boxa m id e (6). To a stirred solution of (S)-
diphenylamino alcohol 2a (1.92 g, 7.5 mmol) and Et3N (2.1 mL,
15 mmol) in THF (10 mL) was added dropwise a solution of
isophthalyl chloride 5 (505 mg, 2.5 mmol) in 60 mL of THF at
room temperature, and the reaction mixture was stirred for 6
h. The resulting white solid was filtered and washed with
water and methanol. It was dried to give 1.51 g of product
N,N′-Bis[1′-(S)-ben zyl-2′,2′-d ip h en yl-2′-h yd r oxyeth yl]-
2,6-p yr id in ed ica r boxa m id e (3b). This was prepared fol-
lowing the general procedure mentioned above: yield 85%; mp
114-116 °C; Rf 0.24 (1:4, EtOAc in petroleum ether); [R]25
D
-115.2° (c 1.25, CHCl3); IR (KBr) 3400, 3040, 1660 cm-1; H
1
NMR (DMSO-d6, 400 MHz) δ 2.78 (d, J ) 12.4 Hz, 2H), 2.93
(dd, J ) 14.0, 3.6 Hz, 2H), 5.39 (dt, J ) 10.4. 1.4 Hz, 2H), 6.42
(s, OH), 7.05 (m, 8H), 7.15 (m, 8H), 7.23 (m, 2H), 7.39 (t, J )
8 Hz, 4H), 7.65 (m, 8H), 7.78 (bs, NH), 7.89 (dd, J ) 8.0, 7.0
Hz, 1H), 8.33 (d, J ) 10.4 Hz, 2H); LCMS (APCI, m/z) 737
(M+ + 1). Anal. Calcd for C49H43N3O4: C, 79.76; H, 5.87; N,
5.69. Found: C, 79.18; H, 5.73; N, 5.72.
(95% yield): mp 182-184 °C; [R]25 -100.5° (c 2.0, DMSO);
D
IR (film) 3400, 3050, 1620 cm-1; 1H NMR (DMSO-d6, 400 MHz)
δ 0.73 (d, J ) 6.8 Hz, 6H), 0.96 (d, J ) 6.8 Hz, 6H), 1.8 (m,
2H), 3.3 (s, OH), 5.12 (d, J ) 10 Hz, 2H), 5.86 (s, 2H, NH),
7.0-7.38 (m, 12H), 7.4-7.6 (m, 8H), 7.68 (dd, J ) 8.0, 2.0 Hz,
1H), 7.89 (dd, J ) 8.0, 2.0 Hz, 2H), 7.99 (s, 1H); LCMS (APCI,
m/z) 641 (M+ + 1). Anal. Calcd for C42H44N2O4: C, 78.72; H,
6.92; N, 4.37. Found: C, 78.31; H, 6.72; N, 4.31.
N,N′-Bis[1′-(S)-m eth yl-2′,2′-d ip h en yl-2′-h yd r oxyeth yl]-
2,6-p yr id in ed ica r boxa m id e (3c): yield 90%; mp 98-100 °C;
Rf 0.71 (1:1, EtOAc in petroleum ether); [R]25 -9.0° (c 1.0,
D
CHCl3); IR (KBr) 3390, 3040, 1660 cm-1; 1H NMR (CDCl3, 400
MHz) δ 1.17 (d, J ) 6.8 Hz, 6H), 2.9 (bs, 2H, OH), 5.22 (m,
2H), 7.13 (m, 2H), 7.26 (m, 6H), 7.38 (t, J ) 7.6 Hz, 4H), 7.56
(m, 8H), 7.91 (dd, J ) 7.6 Hz, 1H), 8.09 (d, J ) 9 Hz, 2H, NH),
8.18 (d, J ) 8 Hz, 2H); LCMS (APCI, m/z) 586 (M+ + 1). Anal.
Calcd for C37H35N3O4: C, 75.87; H, 6.02; N, 7.17; Found: C,
75.41; H, 6.12; N, 7.06.
1,3-Bis[5′,5′-diph en yl-4′-(S)-isopr opyloxazolin -2′-yl] ben -
zen e (7). A solution of amido alcohol 6 (704 mg, 1.1 mmol)
and methanesulfonic acid (425 µL, 6.6 mmol) in CH2Cl2 (20
mL) was refluxed for 6 h while keeping CaH2 in an addition
funnel for removing the water generated during the reaction.
The reaction mixture was diluted with CH2Cl2 (20 mL), washed
with aqueous NaHCO3, water, and brine, and dried. Solvent
removal gave a solid mass that was chromatographed over
silica gel to provide pure product 7 (646 mg, yield 97%): mp
177-180 °C; [R]25D -345.0° (c 1, acetone); IR (KBr) 3060, 1650
N,N′-Bis[1′-(S)-p h en yl-2′,2′-d ip h en yl-2′-h yd r oxyeth yl]-
2,6-p yr id in ed ica r boxa m id e (3d ): yield 94%; mp 158-160
°C; Rf 0.36 (1:3, EtOAc in petroleum ether); [R]25 -341° (c
D
1.0, CHCl3); IR (KBr) 3390, 3030, 1650 cm-1; 1H NMR (CDCl3,
400 MHz) δ 3.25 (s, 2H, OH), 6.09 (d, J ) 8.8 Hz, 2H), 6.92 (d,
J ) 8 Hz, 4H), 7.05-7.42 (m, 22H), 7.73 (d, J ) 8 Hz, 4H),
7.88 (dd, J ) 8.0 Hz, 1H), 8.91 (d, J ) 9.2 Hz, 2H). Anal. Calcd
for C47H39N3O4: C, 79.53; H, 5.54; N, 5.52. Found: C, 79.32;
H, 5.47; N, 5.38.
1
cm-1; H NMR (CDCl3, 400 MHz) δ 0.64 (d, J ) 6.8 Hz, 6H),
1.06 (d, J ) 6.8 Hz, 6H), 1.88 (m, 2H), 4.91 (d, J ) 5.6 Hz,
2H), 7.2-7.6 (m, 21H), 8.26 (dd, J ) 8.0, 1.6 Hz, 2H), 8.80 (s,
1H); MS (FAB, m/z) 606 (M+ + 1), 605 (M+, base peak). Anal.
Calcd for C42H40N2O2: C, 83.39; H, 6.66; N, 4.65. Found: C,
82.98; H, 6.52; N, 4.51.
Gen er a l P r oced u r e for Cycliza tion of Am id o Alcoh ols
(3) to P yr id in e Bis(d ip h en yloxa zolin es) (4). A solution
of amido alcohol 3 (1.1 mmol) and methanesulfonic acid (6.6
mmol) in CH2Cl2 (20 mL) was refluxed for 6 h while keeping
CaH2 in an addition funnel for removing the water generated
during the reaction. The reaction mixture was diluted with
CH2Cl2 (20 mL), washed with aqueous NaHCO3, water, and
brine, and dried. Solvent removal gave a solid mass that was
chromatographed over silica gel to provide pure cyclized
product 4.
Gen er a l P r oced u r e for En a n tioselective Allylic Oxi-
d a tion of Cycloh exen e Usin g P h COOH a n d t-Bu OOH. A
solution of the ligand 4a (0.06 mmol) and copper salt (CuI or
CuCN, 0.05 mmol) in CH3CN (4 mL) was stirred at room
temperature for 1 h. To this red-colored solution were added
benzoic acid (2.5 mmol) and cyclohexene (10 mmol). Then, 70%
t-BuOOH in water (1 mmol) was added dropwise, and during
this time the color of the mixture slowly changed from red to
blue green. The reaction mixture was left at room temperature
for 5 days. After the reaction was over, most of the acetonitrile
was removed in vacuo, and the crude was taken in EtOAc. It
was washed with water, saturated aqueous NaHCO3 solution,
and brine. After drying, solvent removal, and purification over
silica gel, the allylic benzoate 8 (n ) 2) was obtained in a pure
form.
Gen er a l P r oced u r e for En a n tioselective Allylic Oxi-
d a tion of Cycloh exen e w ith ter t-Bu tyl P er ben zoa te in
th e P r esen ce of 4a -Cu (OTf)2. A solution of the ligand 4a
(0.06 mmol) and Cu(OTf)2 (0.05 mmol) in an appropriate
solvent was stirred at room temperature for 1 h. To this blue-
green solution was added cyclohexene (10 mmol). Then, tert-
butyl perbenzoate (1 mmol) was added dropwise under N2
atmosphere, and the reaction mixture was left at room
temperature until the reaction was complete (disappearnce of
tert-butyl perbenzoate by TLC). Workup and purification were
done as above.
Gen er a l P r oced u r e for En a n tioselective Allylic Oxi-
d a tion of Olefin s w ith ter t-Bu tyl P er ben zoa te in th e
P r esen ce of 4a -(Cu OTf)2‚P h H. A solution of the ligand 4a
(36.3 mg, 0.06 mmol) and (CuOTf)2‚PhH (12.6 mg, 0.025 mmol)
in acetone (4 mL) was stirred at room temperature for 1 h. To
this red solution was added an olefin (10 mmol). Then, tert-
butyl perbenzoate (190 µL, 1 mmol) was added dropwise under
N2 atmosphere, and during this time the color of the solution
changed from red to blue-green. The reaction mixture was
left at room temperature until the reaction was complete
(disappearnce of tert-butyl perbenzoate by TLC). During this
time the color of the reaction mixture changed back to red.
Workup and purification were done as above.
2,6-Bis[5′,5′-d ip h en yl-4′-(S)-isop r op yloxa zolin -2′-yl]p y-
r id in e (4a ):17 yield 85%; mp 65-66 °C; Rf 0.55 (1:4, EtOAc
in petroleum ether); [R]25 -233.2° (c 2.7, CHCl3); 1H NMR
D
(CDCl3, 400 MHz) δ 0.68 (d, J ) 6.4 Hz, 6H), 1.06 (d, J ) 6.8
Hz, 6H), 1.95 (m, 2H), 4.89 (d, J ) 4.8 Hz, 2H), 7.28 (m, 8H),
7.36 (m, 8H), 7.6 (d, J ) 8 Hz, 4H), 7.96 (t, J ) 7.2 Hz, 1H),
8.21 (d, J ) 8 Hz, 2H).
2,6-Bis[5′,5′-d ip h en yl-4′-(S)-ben zyloxa zolin -2′-yl]p yr i-
d in e (4b): yield 85%; mp 101-102 °C; Rf 0.48 (1:4, EtOAc in
petroleum ether); [R]25 -328.0° (c 1, CHCl3); IR (KBr) 3000,
D
1620 cm-1
;
1H NMR (CDCl3, 80 MHz) δ 2.8 (d, J ) 7.5 Hz,
4H), 5.15 (t, J ) 7.5 Hz, 2H), 6.8-7.7 (m, 30H), 7.98 (dd, J )
7.0, 6.0 Hz, 1H), 8.18 (d, J ) 8 Hz, 2H); MS (FAB, m/z) 702
(M+ + 1, base peak). Anal. Calcd for C49H39N3O2: C, 83.85;
H, 5.60; N, 5.98. Found: C, 83.52; H, 5.80; N, 5.73.
2,6-Bis[5′,5′-d ip h en yl-4′-(S)-m eth yloxa zolin -2′-yl]p yr i-
d in e (4c). This was prepared as per the general procedure
mentioned above: yield 45% as a sticky material; Rf 0.37 (1:3,
EtOAc in petroleum ether); [R]25 -112.1° (c 2.5, CHCl3); IR
D
(film) 3000, 1710 cm-1; H NMR (CDCl3, 300 MHz) δ 2.4 (d,
1
6H), 5.12 (m, 2H), 6.75-7.5 (m, 20H), 7.99 (t, J ) 8 Hz, 1H),
8.27 (d, J ) 9 Hz, 1H), 8.37 (d, J ) 9 Hz, 1H); MS (FAB, m/z)
550 (M+ + 1, base peak). Anal. Calcd for C37H31N3O2: C,
80.84; H, 5.68; N, 7.64. Found: C, 80.52; H, 5.35; N, 7.35.
2,6-Bis[5′,5′-d ip h en yl-4′-(S)-p h en yloxa zolin -2′-yl]p yr i-
d in e (4d ). This was prepared as per the general procedure
mentioned above: yield 67%; mp 99-101 °C; Rf 0.27 (1:4,
EtOAc in petroleum ether); [R]25 -152.0° (c 1.0, CHCl3); IR
D
(film) 3040, 1680 cm-1; H NMR (CDCl3, 400 MHz) δ 6.12 (s,
1
1H), 6.8-7.21 (m, 20H), 7.28-7.45 (m, 8H), 7.6 (m, 2H), 7.97
(dd, J ) 8.0 Hz, 1H), 8.31 (m, 2H), 9.88 (s, 1H); LCMS (APCI,
Gen er a l P r oced u r e for En a n tioselective Allylic Oxi-
d a t ion of Olefin s w it h ter t-Bu t yl P er b en zoa t e in t h e

Asymmetric Kharasch Reaction
J . Org. Chem., Vol. 63, No. 9, 1998 2967
P r esen ce of 4a -Cu (OTf)2 a n d P h NHNH2. A blue-green
solution of the ligand 4a (36 mg, 0.06 mmol) and Cu(OTf)2 (18
mg, 0.05 mmol) in acetone (4 mL) was stirred at room
temperature for 1 h. Phenylhydrazine (6µL, 0.06 mmol) was
added, and the color of the solution changed from blue-green
to red (an indication of reduction of Cu(II) to Cu(I)). After 5
min, an olefin (10 mmol) was added. Then, tert-butyl perben-
zoate (1 mmol) was added dropwise under N2 atmosphere and
the reaction mixture was left at room temperature until the
reaction was complete (disappearance of tert-butyl perbenzoate
by TLC). Workup and purification were done as above.
Gen er a l P r oced u r e for Allylic Oxid a t ion of Olefin s
w ith ter t-Bu tyl P er ben zoa te in th e P r esen ce of 4a -
(Cu OTf)2‚P h H a n d P h NHNH2. A solution of the ligand 4a
(36.3 mg, 0.06 mmol) and (CuOTf)2‚PhH (12.6 mg, 0.025 mmol)
in acetone (4 mL) was stirred at room temperature for 1 h. To
this red solution was added phenylhydrazine (6 µL, 0.06
mmol), and the solution was stirred for 10 min. After this,
an olefin (10 mmol) was added. Then, tert-butyl perbenzoate
(1 mmol) was added dropwise under N2 atmosphere, and
during this time the color of the solution changed from red to
blue-green. The reaction mixture was left at room tempera-
ture until the reaction was complete (disappearnce of tert-butyl
perbenzoate by TLC). During this time the color of the
reaction mixture again changed to red. Workup and purifica-
tion were done as above.
Gen er a l P r oced u r e for Allylic Oxid a t ion of Olefin s
w ith ter t-Bu tyl P er ben zoa te in th e P r esen ce of 4a -
(Cu OTf)2‚P h H a n d 4Å Molecu la r Sieves. A solution of the
ligand 4a (36.3 mg, 0.06 mmol) and (CuOTf)2‚PhH (12.6 mg,
0.025 mmol) in acetone (4 mL) was stirred at room tempera-
ture for 1 h. To this red solution were added 10-15 grains of
4 Å molecular sieves and an olefin (10 mmol). Then, tert-butyl
perbenzoate (190 µL, 1 mmol) was added dropwise under N2
atmosphere, and during this time the color of the solution
changed from red to blue-green. The reaction mixture was
left at room temperature until the reaction was complete
(disappearance of tert-butyl perbenzoate by TLC). After
completion of the reaction, the color of the reaction mixture
changed back to red. Workup and purification were done as
above.
Gen er a l P r oced u r e for Allylic Oxid a t ion of Olefin s
w ith ter t-Bu tyl P er ben zoa te in th e P r esen ce of 4a -
(Cu OTf)2‚P h H , P h en ylh yd r a zin e, a n d 4 Å Molecu la r
Sieves. A solution of the ligand 4a (36.3 mg, 0.06 mmol) and
(CuOTf)2‚PhH (12.6 mg, 0.025 mmol) in acetone (4 mL) was
stirred at room temperature for 1 h. To this red solution was
added phenylhydrazine (0.06 mmol), and the mixture was
stirred for 10 min. Then, 10-15 grains of 4 Å molecular sieves
and an olefin (10 mmol) were added. Then, tert-butyl perben-
zoate (190 µL, 1 mmol) was added dropwise under N2 atmo-
sphere, and during this time the color of the solution changed
from red to blue-green. The reaction mixture was left at room
temperature until the reaction was complete (disappearance
of tert-butyl perbenzoate by TLC). After completion of the
reaction, the color of the reaction mixture again changed back
to red. Workup and purification were done as above.
Gen er a l P r oced u r e for Allylic Oxid a t ion of Olefin s
w ith ter t-Bu tyl P er ben zoa te in th e P r esen ce of 4a -Cu -
(OTf)2, P h en ylh yd r a zin e, a n d 4 Å Molecu la r Sieves. A
solution of the ligand 4a (36.3 mg, 0.06 mmol) and Cu(OTf)2
(18 mg, 0.05 mmol) in acetone (4 mL) was stirred at room
temperature for 1 h. To this blue-green solution was added
phenylhydrazine (0.06 mmol), and the mixture was stirred for
10 min. During this time, the color of the solution changed
from blue-green to red (an indication for reduction of Cu(II)
to Cu(I) species). Then, 10-15 grains of 4 Å molecular sieves
and an olefin (10 mmol) were added. Then, tert-butyl perben-
zoate (190 µL, 1 mmol) was added dropwise under N2 atmo-
sphere, and during this time the color of the solution changed
from red to blue-green. The reaction mixture was left at room
temperature until the reaction was complete (disappearance
of tert-butyl perbenzoate by TLC). After completion of the
reaction, the color of the reaction mixture again changed back
to red. Workup and purification were done as above.
Gen er a l P r oced u r e for Hyd r olysis of (S)-Allylic Ben -
zoa tes. A solution of (S)-allylic benzoate (0.5 mmol) in 0.4 M
KOH solution in MeOH (4 mL) was kept at 0-3 °C until the
TLC showed complete disappearnce of the benzoate (10-30
h). After the reaction was over, methanol was removed in
vacuo, and the crude mixture was taken in CH2Cl2 (15 mL).
It was washed with water and brine and dried. Solvent
removal and filtration through a small plug of silica gel gave
pure (S)-allylic alcohol 9.10
(S)-2-Cyclop en ten yl-1-ben zoa te. It was obtained in a
maximum of 60% ee. The optical purity was determined by
HPLC on chiralcel OD column [hexane/2-propanol 99.95:0.05;
flow rate 0.5 mL/min; tR ) 27.48 min (S), 34.75 min (R)]: [R]25
D
-116.8° (c 7.5, CHCl3) [lit.8d,e (93% ee); [R]25 -179.0° (c 0.37,
D
CHCl3)].
(S)-2-Cycloh exen yl-1-ben zoa te. It was obtained in a
maximum of 86% ee. The optical purity was determined by
HPLC on chiralcel OD-H column [hexane/2-propanol 99.5:0.5;
tR ) 17.26 min (R), 18.78 min (S)]; [R]25D -157.0° (c 2.8, CHCl3)
[lit.8d,e (66% ee); [R]25 -118.0° (c 0.45, CHCl3)].
D
(S)-2-Cycloh ep ten yl-1-ben zoa te. It was obtained in a
maximum of 82% ee, which was determined by HPLC on
chiralcel OD-H column [heptane/2-propanol 99.9:0.1; tR ) 22.97
min (S), 24.85 min (R)]; [R]25D -38.2° (c 1, CHCl3) [lit.8d,e (60%
ee); [R]25 -29.0° (c 0.24, CHCl3)].
D
(S)-2-Cycloocten yl-1-ben zoa te. It was obtained in a
maximum of 82% ee, which was determined by Mosher ester23
of the corresponding alcohol: [R]25 +72.6° (c 1.25, CHCl3)
D
[lit.8d,e (64% ee); [R]25 +55.0° (c 0.11, CHCl3)].
D
Ack n ow led gm en t. This work has been supported
by a grant from the Department of Science and Tech-
nology (under SERC). We thank Professors A. Pfaltz,
P. G. Andersson, and D. Basavaiah for help in running
some of our samples on chiral HPLC columns. We also
thank Professors Kochi and Beckwith for discussions
on the mechanism of the Kharasch
reaction. G.S. thanks C.S.I.R. for the award of a senior
research fellowship.
J O972132P