Chiral synthesis via organoboranes. 48. Efficient synthesis of trans- fused bicyclic and cyclic ketones and secondary alcohols in high optical purities via asymmetric cyclic hydroboration with isopinocampheylchloroborane etherate

Article abstract of DOI:10.1021/jo981040c

Highly stereo- and enantioselective annelation has been achieved for the synthesis of trans-fused bicyclic and cyclic ketones via the asymmetric cyclic hydroboration of suitable cyclic dienes, such as 1-allyl-1- cycloalkenes or 1-vinyl-1-cycloalkenes and appropriate acyclic 1,4-dienes, respectively, with enantiomerically pure isopinocampheylchloroborane etherate (IpcBHCl·Et₂O). The IpcBHCl· Et₂O (an 86-90% equilibrium mixture) was readily synthesized by the reaction of an equivalent amount of hydrochloric acid in ethyl ether (Et₂O) with optically pure isopinocampheylborane (IpcBH₂). The hydroboration of the terminal double bond of a representative diene with IpcBHCl·Et₂O readily provided the corresponding isopinocampheylalkylchloroborane (IpcRBCl). Subsequent hydridation of the IpcRBCl with lithium aluminum hydride (LAH, 0.25 equiv) at -20 or -25 °C generated the intermediate isopinocampheylalkylborane (IpcRBH) almost instantly, which then underwent a rapid stereospecific and enantioselective intramolecular cyclic hydroboration to provide the intermediate cyclic trialkylborane. This trialkylborane, on treatment with an aldehyde, liberated the optically pure auxiliary as α-pinene (readily recovered for recycle) to provide the corresponding cyclic borinate ester. This ester reacted smoothly with α,α-dichloromethyl methyl ether (DCME) in the presence of a hindered base (the DCME reaction) to yield, after oxidation with buffered hydrogen peroxide, the trans-fused bicyclic or cyclic ketone in high enantiomeric excess (ee). In another improved approach, in situ generated IpcBHCl·Et₂O, from the reduction of isopinocampheyldichloroborane (IpcBCl₂) with trimethylsilane (Me₃SiH), in the presence of representative dienes in Et₂O provided considerably improved optical yields of the bicyclic and cyclic ketones. The trialkylboranes obtained from suitable acyclic dienes can be easily protonolyzed to provide the secondary alcohols in high ee.

Full text of DOI:10.1021/jo981040c

8276
J . Org. Chem. 1998, 63, 8276-8283
Ch ir a l Syn th esis via Or ga n obor a n es. 48. Efficien t Syn th esis of
Tr a n s-F u sed Bicyclic a n d Cyclic Keton es a n d Secon d a r y Alcoh ols
in High Op tica l P u r ities via Asym m etr ic Cyclic Hyd r obor a tion
w ith Isop in oca m p h eylch lor obor a n e Eth er a te
Ulhas P. Dhokte,1a Pradip M. Pathare,1b Verinder K. Mahindroo,1c and Herbert C. Brown*
H. C. Brown and R. B. Wetherill Laboratories of Chemistry, Purdue University,
West Lafayette, Indiana 47907
Received J une 1, 1998
Highly stereo- and enantioselective annelation has been achieved for the synthesis of trans-fused
bicyclic and cyclic ketones via the asymmetric cyclic hydroboration of suitable cyclic dienes, such
as 1-allyl-1-cycloalkenes or 1-vinyl-1-cycloalkenes and appropriate acyclic 1,4-dienes, respectively,
with enantiomerically pure isopinocampheylchloroborane etherate (IpcBHCl‚Et2O). The IpcBHCl‚
Et2O (an 86-90% equilibrium mixture) was readily synthesized by the reaction of an equivalent
amount of hydrochloric acid in ethyl ether (Et2O) with optically pure isopinocampheylborane
(IpcBH2). The hydroboration of the terminal double bond of a representative diene with IpcBHCl‚
Et2O readily provided the corresponding isopinocampheylalkylchloroborane (IpcRBCl). Subsequent
hydridation of the IpcRBCl with lithium aluminum hydride (LAH, 0.25 equiv) at -20 or -25 °C
generated the intermediate isopinocampheylalkylborane (IpcRBH) almost instantly, which then
underwent a rapid stereospecific and enantioselective intramolecular cyclic hydroboration to provide
the intermediate cyclic trialkylborane. This trialkylborane, on treatment with an aldehyde, liberated
the optically pure auxiliary as R-pinene (readily recovered for recycle) to provide the corresponding
cyclic borinate ester. This ester reacted smoothly with R,R-dichloromethyl methyl ether (DCME)
in the presence of a hindered base (the DCME reaction) to yield, after oxidation with buffered
hydrogen peroxide, the trans-fused bicyclic or cyclic ketone in high enantiomeric excess (ee). In
another improved approach, in situ generated IpcBHCl‚Et2O, from the reduction of isopinocam-
pheyldichloroborane (IpcBCl2) with trimethylsilane (Me3SiH), in the presence of representative
dienes in Et2O provided considerably improved optical yields of the bicyclic and cyclic ketones.
The trialkylboranes obtained from suitable acyclic dienes can be easily protonolyzed to provide the
secondary alcohols in high ee.
Hydroboration of alkenes is one of the fundamentally
general stereospecific synthesis of trans-fused bicyclic
ketones via the cyclic hydroboration-carbonylation pro-
tocol.4 A noteworthy feature of this methodology is the
stereospecific synthesis of thermodynamically disfavored
(()-trans-perhydro-1-indanone (1) (eq 1).4b This reaction
has shown considerable promise for the synthesis of cyclic
systems from appropriate dienes as shown in eq 2.5b
novel reactions in organic synthesis to provide organobo-
ranes readily transformed into an array of synthetically
useful compounds of interest.2 Since the development of
optically pure R-pinene-derived borane reagents, a vari-
ety of procedures have become available for the enanti-
oselective version of this reaction.3 On the other hand
boron annulation via cyclic hydroboration of suitable
dienes, developed in our group,4 has emerged as an
important synthetic tool in the synthesis of natural
products.5,6 The thexylborane (ThxBH2) reagent has been
used to hydroborate representative dienes to achieve a
(1) Present addresses: (a) Chemical Development, Bristol-Myers
Squibb Co., Syracuse, NY 13221. (b) Department of Radiation Oncol-
ogy, University of Washington, Medical Center, Seattle, WA 98195.
(c) Department of Drug Metabolism, G. D. Searle & Co., 4901 Searle
Parkway, Skokie, IL 60077.
(2) (a) Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21, 287.
(b) Matteson, D. S. Synthesis 1986, 973.
(3) (a) Brown, H. C.; Ramachandran, P. V. Advances in Asymmetric
Synthesis; Hassner, A., Ed.; J AI Press: Greenwich, CT, 1995; Vol. 1,
pp 147-210. (b) Brown, H. C.; Ramachandran, P. V. J . Organomet.
Chem. 1995, 500, 1.
(4) (a) Brown, H. C.; Negishi, E. J . Am. Chem. Soc. 1967, 89, 5477.
(b) Brown, H. C.; Negishi, E. Chem. Commun. 1968, 594.
(5) (a) Bryson, T. A.; Reichel, C. J . Tetrahedron Lett. 1980, 2381.
(b) Welch, M. C.; Bryson, T. A. Tetrahedron Lett. 1988, 521. (c)
Pattenden, G.; Smithies, A. J .; Walter, D. S. Tetrahedron Lett. 1994,
35, 2413.
Asymmetric hydroboration has been studied quite
extensively. However, no effort has been made to study
the enantioselective version of cyclic hydroboration as a
powerful and convenient synthetic tool for the stereo- and
enantioselective preparation of synthetically useful trans-
fused polycyclic systems. Since many natural products
possess such cyclic systems in their structures,5 a simple
and efficient method to achieve their synthesis in highly
stereocontrolled fashion is highly desirable. Thus, the
(6) (a) Reichert, C. F.; Pye, W. E.; Bryson, T. A. Tetrahedron 1981,
37, 2441. (b) Levine, E. J .; Bryson, T. A. Heterocycles 1982, 18, 271.
10.1021/jo981040c CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/21/1998

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 63, No. 23, 1998 8277
Sch em e 1
importance of this area of research led us to examine the
synthesis of chiral trans-1-decalone by asymmetric cyclic
hydroboration of 1-allyl-1-cyclohexene (4) with IpcBH2
(2)7,8 as well as the improved IpcBHCl‚Et2O (3) reagent
in high enantiomeric purity.9
In this paper, we wish to report a detailed account of
our research on the asymmetric cyclic hydroboration of
appropriate dienes, viz., 1-allyl-1-cycloalkenes and 1-vinyl-
1-cycloalkenes, with IpcBH2 (2) and with IpcBHCl‚Et2O
(generated by two different but simple operations). We
also wish to report the application of this reaction for the
synthesis of cyclic ketones and secondary alcohols in
significantly high optical purities.
Optically pure isopinocampheylborane (2) was conve-
niently prepared via hydroboration of R-pinene.7 Cyclic
hydroboration of the diene 4 with IpcBH2 (2) in Et2O at
-20 °C formed the corresponding cyclic trialkylborane
5. The trialkylborane on treatment with acetaldehyde13
underwent a clean, facile elimination of the chiral auxil-
iary, R-pinene, to form the corresponding cyclic borinate
ester 6. The ester 6 reacted smoothly with R,R-dichlo-
romethyl methyl ether (DCME) in the presence of lithium
tert-butoxide (the DCME reaction)14 to yield, after oxida-
tion with buffered hydrogen peroxide, optically active (+)-
trans-1-decalone in g99% de and 54% ee (Scheme 1).
The asymmetric induction realized with IpcBH2 (2) was
only moderate. This unsatisfactory result led us to
examine modification of the IpcBH2 reagent in the hope
of achieving improved optical yields. Literature reports15
suggest that the steric and electronic environment around
the boron atom in pinene-based reagents must be critical
for achieving a high degree of stereoselection in asym-
metric hydroboration. Accordingly, we decided to explore
the effect of introducing a chlorine atom into the IpcBH2
reagent. An advantage of IpcBHCl is that it would
permit sequential hydroboration. Thus, the reaction of
IpcBH2 with a stoichiometric amount of ethereal hydro-
gen chloride provided isopinocampheylchloroborane ether-
ate (IpcBHCl‚Et2O) (2) in Et2O at -5 °C. Systematic
investigation of this new reagent showed that IpcBHCl‚
Et2O exists in equilibrium with small amounts of IpcBH2
and IpcBCl2‚Et2O (8) (∼5-7% each)16 (eq 3).
Resu lts a n d Discu ssion
Optically active carbonyl compounds, bearing a ste-
reogenic center R to the carbonyl group, are important
synthons for a number of natural and unnatural prod-
ucts. Earlier reports describe tedious routes for the
synthesis of optically active trans-1-decalone (7) involving
resolution procedures10,11 and for substituted ketones as
well. For example, Djerassi et al.10 synthesized optically
active trans-1-decalone (7) by the optical resolution of (()-
cis,cis-1-decalol, followed by oxidation to the correspond-
ing cis,cis-1-decalone, equilibrated to trans-1-decalone of
70% optical purity. Enders et al.12 reported the synthesis
of optically active R-substituted ketones by the conversion
of the ketones into the chiral hydrazones, which under-
went metalation with lithium diisopropylamide to the
metal derivatives. These, upon alkylation followed by
ozonolysis or hydrolysis, provided chiral R-substituted
ketones. Thus to explore the full scope and the generality
of the asymmetric cyclic hydroboration process, we
decided to synthesize in high ee representative trans-
fused bicyclic and cyclic ketones as well as related
secondary alcohols.
Syn th esis of Tr a n s-Fu sed Bicyclic Keton es. Thex-
ylborane (ThxBH2) has been utilized to synthesize trans-
fused bicyclic ketones in a stereospecific manner from the
corresponding cyclic dienes (eq 1).4 We decided to
examine the possibility of achieving asymmetric cyclic
hydroboration of dienes by replacing the thexyl group of
ThxBH2 by the optically pure isopinocampheyl (Ipc) group
from R-pinene, IpcBH2 (2).7 Thus, the synthesis of
optically active trans-1-decalone (7) was selected as a trial
case to test the practicality of achieving asymmetric cyclic
hydroboration of a representative diene, 1-allyl-1-cyclo-
hexene (4) (Scheme 1).
Thus, the hydroboration of 1-allyl-1-cyclohexene (4)
with IpcBHCl‚Et2O provided the corresponding IpcRBCl
9 predominantly, along with only trace amounts of the
trialkylborane 5. This dialkylchloroborane (9) on treat-
ment with 0.25 equiv of LiAlH4 at -20 °C underwent
smooth hydridation17 with the precipitation of LiCl,
(7) (a) Brown, H. C.; Schwier, J . R.; Singaram, B. J . Org. Chem.
1928, 43, 4395. (b) Brown, H. C.; J adhav, P. K.; Mandal, A. K. J . Org.
Chem. 1982, 47, 5074.
(8) This molecule actually exists in solution as a dimer. However,
it is convenient to represent in the monomeric form.
(9) Brown, H. C.; Mahindroo, V. K.; Dhokte, U. P. J . Org. Chem.
1996, 61, 1906.
(10) Djerassi, C.; Staunton, J . J . Am. Chem. Soc. 1961, 83, 736.
(11) Fernandez, F.; Kirk, D. N.; Scopes, M. J . Chem. Soc., Perkin
Trans. 1 1974, 1, 18.
(13) (a) Brown, H. C.; J adhav, P. K.; Desai, M. C. J . Am. Chem.
Soc. 1982, 104, 4303. (b) Brown, H. C.; J adhav, P. K.; Desai, M. C. J .
Org. Chem. 1982, 47, 4583.
(14) (a) Carlson, B. A.; Brown, H. C. J . Am. Chem. Soc. 1973, 95,
6876. (b) Brown, H. C.; Carlson, B. A. J . Org. Chem. 1973, 38, 2422.
(15) (a) Houk, K. N.; Rondan, N. G.; Wu, Y.-D.; Metz, J . T.; Paddon-
Row, M. N. Tetrahedron 1984, 40, 2257. (b) Egger, M.; Keese, R. Helv.
Chim. Acta 1987, 70, 1843.
(12) Enders, D.; Eichenauer, H. Angew. Chem., Int. Ed. Engl. 1976,
15, 549.
(16) Dhokte, U. P.; Kulkarni. S. V.; Brown, H. C. J . Org. Chem. 1996,
61, 5140.

8278 J . Org. Chem., Vol. 63, No. 23, 1998
Dhokte et al.
Sch em e 2
Sch em e 4
Sch em e 3
followed by the DCME reaction-oxidation as described
earlier furnished the desired trans-1-decalone (7) in
g99% ee (Scheme 4).21
For convenience, the kinetic resolution methodology
was further extended for the chiral synthesis of other
trans-fused bicyclic systems to provide the optically active
bicyclic ketones 15-19 from appropriate dienes. The
results are summarized in Table 1. By application of the
upgradation methodology and controlled treatment with
an aldehyde, the ee’s of ketones 15-17 were conveniently
increased to 79%, 92%, and 90%, from their initial values
of 69%, 76%, and 76%, respectively (Chart 1).
Lower ee values, i.e., 31% and 56%, were realized for
the formation of trans-fused bicyclic ketones, 19 and 18,
containing a five-membered ring, with IpcBHCl. How-
ever, the upgradation methodology provided moderate to
excellent optical induction for bicyclic ketones containing
the six-membered ring.
forming the corresponding dialkylborane 10 in situ,
which then underwent a facile intramolecular asym-
metric cyclic hydroboration to furnish the desired cyclic
trialkylborane 5. Elimination of (+)-R-pinene from 5 by
treatment with acetaldehyde, followed by the DCME
reaction as described earlier, afforded the (+)-trans-1-
decalone (7) in g99% de and 84% ee (Scheme 2).
Thus, the use of preformed IpcBHCl‚Et2O improved the
optical yield of (+)-trans-1-decalone (7) to 84% ee. We
had previously established that the controlled treatment
of diastereomeric isopinocampheylalkylborinate esters
with an aldehyde results in a preferred reaction with the
major isomer, upgrading the optical purity of the product
borinate ester via kinetic resolution.18 In a similar
approach, indeed, the treatment of the diastereomeric
trialkylborane 5 (92:8) with 0.7 equiv of PhCHO, followed
by applying the DCME reaction19 to the resulting bori-
nate ester 11, provided (+)-trans-1-decalone (7) in g99%
ee (Scheme 3).
In the second approach, optically pure trans-1-decalone
(7) was prepared by upgradation of the intermediate
borinate ester 6. It is known that borinate esters react
with amino alcohols to form crystalline adducts.20 Thus,
the treatment of borinate ester 6 with a optically active
(S)-(+)-2-pyrrolidinemethanol (12) in Et2O at 24 °C
provided the diastereomeric adducts. The major diaste-
reomer 13 crystallized out, leaving the minor isomer in
the solution. Crystalline 13 was isolated and washed
with Et2O. Treatment with HCl provided the corre-
sponding borinic acid and the amino alcohol hydrochlo-
ride. The borinic acid, thus obtained, on esterification
In Situ Gen er a tion of Ip cBHCl‚Et2O fr om Red u c-
tion of Ip cBCl2 w ith Me3SiH in Et2O a s a n Im p r oved
Ap p r oa ch F or Asym m etr ic Cyclic Hyd r obor a tion .
Although synthesis of trans-1-decalone in g99% ee was
achieved by our upgradation protocol, we decided to
investigate the formation of pure IpcBHCl. Since the
preformed IpcBHCl‚Et2O (g99% ee, an 85-90% equilib-
rium mixture, eq 3) reagent provided ketone 7 in moder-
ate 84% ee, it was thought that the decreased ee might
be due to the ∼5-7% IpcBH2 present in the equilibrium
mixture.16 Therefore, we undertook to modify the syn-
thesis of IpcBHCl‚Et2O. It was anticipated that the
asymmetric cyclic hydroboration of 1-allyl-1-cyclohexene
with pure IpcBHCl‚Et2O might provide high ee for trans-
1-decalone. Thus, stable and optically pure isopinocam-
pheyldichloroborane22 (IpcBCl2, g99% ee) was prepared
from the reaction of boron trichloride (BCl3), trimethyl-
silane, and (+)-R-pinene (g99% ee).23 In situ reduction
of IpcBCl2 with trimethylsilane provided the intermediate
IpcBHCl which immediately hydroborated diene 4, al-
ready present in the reaction, in Et2O at -5 °C, to provide
the dialkylchloroborane 9 exclusively, without contami-
nation with trialkylborane 5 (Scheme 5).
The pure dialkylchloroborane intermediate 9 (g99%)
was subjected to hydridation with 0.25 equiv of LAH at
-25 °C in Et2O for 4 h to provide the trialkylborane 5.
This trialkylborane 5, following the same reaction se-
(17) (a) Kulkarni, S. U.; Lee, H. D.; Brown, H. C. J . Org. Chem.
1980, 45, 4542. (b) Brown, H. C.; Kulkarni, S. U. J . Organomet. Chem.
1980, 218, 299.
(18) J oshi, N. N.; Pyun, C.; Mahindroo, V. K.; Singaram, B.; Brown,
H. C. J . Org. Chem. 1992, 57, 504.
(19) The DCME reaction-oxidation process transforms borinate
esters 11 into ketones and trialkylboranes into tertiary alcohols. See
also ref 14.
(20) (a) Brown, H. C.; Bhat, K. S.; J adhav, P. K.; J . Chem. Soc.,
Perkin Trans. 1 1991, 2633. (b) Brown, H. C.; Vara Prasad, J . V. N. J .
Org. Chem. 1986, 51, 4526.
(21) For practical reasons we recommend the earlier in situ one-
pot method of upgrading the borinate ester by the controlled treatment
with an aldehyde.
(22) Brown, H. C.; Ramachandran, P. V.; Chandrasekharan, J .
Heteroatom Chem. 1995, 6, 117.
(23) Soundararajan, R.; Matteson, D. S. Organometallics 1995, 14,
4157.

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 63, No. 23, 1998 8279
Ta ble 1. Da ta for th e Op tica lly Active Tr a n s-F u sed Bicyclic Keton es Obta in ed via Asym m etr ic Cyclic Hyd r obor a tion of
Su ita ble Dien es
dienea
bicyclic ketonesb
yield (%)c
% eed
[R]D (c, solvent)
1-allyl-1-cyclohexene
7e
76
65f
51g
74h
67
84
g99f
g99g
g99h
69
+8.2° (0.55, EtOH)
+10° (0.57, EtOH)
+10o(0.53, EtOH)
+10.2o(0.53, EtOH)
-7.6o(1.09, CDCl3)
-8.6o(1.01, CDCl3)
-8.7o(1.02, CDCl3)
+15.2o(1.30, CDCl3)
+18.5o(1.46, CDCl3)
+5.9o(1.13, EtOH)
+7.4o(0.84, EtOH)
+5.8o(1.00, EtOH)
+112o(1.64, CDCl3)
+78.2o(1.64, CDCl3)
1-allyl-1-cyclopentene
15i
55f
68h
69
79f
81h
76
1-allyl-1-cycloheptene
1-allyl-1-cyclooctene
16i
17i
53f
62
92f
76
49f
59h
66
90f
72h
56j
1-vinyl-1-cyclohexene
1-vinyl-1-cycloheptene
18i
19i
66
31j
a
b
Dienes prepared by literature procedure and purified by fractional distillation.29 Stereoisomeric purities established by capillary
GC (SPB-5 column). c Isolated. Determined by analyzing dia-stereomeric ketals on capillary GC (SPB-5, column). e Analytical sample
d
was purified on preparative GC. f Upgradation via kinetic resolution. g Upgradation via chelate formation. Obtained by in situ generated
h
i
j
IpcBHCl‚Et2O method. Analytical sample was purified by HPLC. Determined by analyzing menthyl carbonate of secondary alcohol on
capillary GC (SPB-5 column).
Ch a r t 1
rotrimethylsilane at -10 °C. The diastereomeric ketals
separated well on capillary GC, in comparison with 1:1
racemic ketals obtained from the racemic ketones indi-
cating no kinetic resolution had taken place (eq 4).
However, diastereomeric ketals from the ketones 18
and 19 did not resolve on a capillary GC. Therefore, an
alternative method had to be worked out to determine
their ee values. Organoboranes react readily with car-
boxylic acids to liberate the corresponding alkanes. The
first alkyl group of a trialkylborane is protonolyzed easily,
followed by increased difficulty in the removal of the
second and third alkyl groups. The protonolysis reaction
proceeds with retention of stereochemistry of the carbon
center.25 Thus, taking advantage of this novel chemistry,
the trialkylboranes intermediates, involved in the syn-
thesis of these ketones, were subjected to selective
protonolysis of the primary C-B bond with acetic acid,
followed by oxidation to form the corresponding second-
ary alcohols. The alcohols were then converted to the
menthyl carbonate26 derivatives, which resolved well on
a capillary GC. The ee of the alcohols thus obtained
reflected the optical yield of the ketones obtained from
these trialkylboranes (eq 5).
Sch em e 5
quence as shown in Scheme 2 provided (+)-trans-1-
decalone (7) in g99% de and ee. Thus, we achieved the
synthesis of (+)-trans-1-decalone in essentially g99% ee
from the in situ generated IpcBHCl produced in the
reaction of IpcBCl2‚Et2O with trimethylsilane in Et2O in
the presence of 1-allyl-1-cyclohexene! Under similar
conditions, this procedure provided ketone 15 in 81% ee,
a higher value than that realized with preformed IpcBHCl‚
Et2O. On the other hand, ketone 17 was obtained in 76%
ee, a value comparable with that obtained with preformed
IpcBHCl‚Et2O.
Deter m in a tion of En a n tiom er ic Excess of Bicy-
clic Keton es. To our knowledge, of all the examples of
the bicyclic ketones synthesized, only trans-1-decalone
is known in optically pure form. Therefore, to determine
the enantiomeric purities of the bicyclic ketones 7 and
15-17, these ketones were conveniently converted into
their corresponding diastereomeric ketals24 by reaction
with optically active (2S,3S)-(+)-2,3-butanediol and chlo-
(24) Brown, H. C.; Srebnik, M.; Bakshi, R. K.; Cole, T. E. J . Am.
Chem. Soc. 1987, 109, 5420.
(25) (a) Brown, H. C.; Murray K. J . J . Am. Chem. Soc. 1959, 81,
4108. (b) Brown, H. C.; Murray K. J . J . Org. Chem. 1961, 26, 631. (c)
Brown, H. C.; Murray, K. J . Tetrahedron 1986, 42, 5497.
(26) Westley, J . W.; Halpern, B. J . Org. Chem. 1968, 33, 3978.

8280 J . Org. Chem., Vol. 63, No. 23, 1998
Dhokte et al.
Sch em e 6
Ch a r t 2
Sch em e 8
Sch em e 7
Stereoisomeric purities of the ketones 7 and 15-19
were established by epimerization of the products in the
presence of sodium methoxide followed by GC analyses
of the equilibrated mixtures and the isolated ketones.4b
In all cases the data revealed the absence of the cis-
isomers.
Assign m en t of Ab solu t e Con figu r a t ion . Kirk et
al.11 have established the absolute configuration of
trans-1-decalone (7). Thus, in accord with the sign of
the rotation of this ketone 7, obtained by the asym-
metric cyclic hydroboration, its absolute configuration
should be (9R,10S). In analogy with trans-1-decalone (7),
the absolute configuration of ketones 15-19 can be
correlated.
Syn th esis of 2-Or ga n ylcyclop en ta n on es in High
Op tica l P u r ities via Asym m etr ic Cyclic Hyd r obo-
r a tion of Su ita ble 1,4-Dien es. After achieving moder-
ate to excellent success in the asymmetric cyclic hydrob-
oration of cyclic dienes, we decided to test the utility of
the process for the synthesis of R-substituted cyclopen-
tanones via asymmetric cyclic hydroboration of a repre-
sentative examples of acyclic dienes, such as appropriate
1,4-dienes. For this study, asymmetric cyclic hydrobo-
ration of trans-1,4-hexadiene with IpcBH2 (2) was se-
lected as a typical example. The reaction was carried
out at -25 °C in Et2O to provide the corresponding
trialkylborane 20, which upon the series of reactions as
described earlier for trialkylborane 5 in Schemes 1 and
2, provided optically active 2-ethylcyclopentanone (22) in
64% ee (Scheme 6).
metric cyclic hydroboration of 1,4-pentadiene and 1,4-
hexadiene with in situ generated IpcBHCl, as described
in Scheme 5, provided 2-methyl- (25) and 2-ethylcyclo-
pentanones (22) in 51% and 79% ee, respectively. To
establish the generality of this methodology, asymmetric
cyclic hydroborations of representative 1,4-dienes were
performed with preformed IpcBHCl‚Et2O to achieve the
synthesis of 2-organylcyclopentanones (26-29) in moder-
ate ee (Chart 2).
We anticipate that it would be possible to upgrade the
ee of these products by following the kinetic resolution
shown in Scheme 3 and by the chelation method shown
in Scheme 4.
Deter m in a tion of Op tica l P u r ities of 2-Or ga n yl-
cyclop en ta n on es a n d Syn th esis of Ch ir a l Secon d -
a r y Alcoh ols. Organoboranes react readily with car-
boxylic acids to liberate the corresponding alkanes
(protonolysis reaction) with retention of stereochemistry
of the carbon center.25 Thus, trialkylboranes, a product
of asymmetric cyclic hydroboration of acyclic 1,4-dienes,
were treated with glacial acetic acid at ambient temper-
ature and the intermediate species were further subjected
to alkaline peroxide oxidation to provide the desired
secondary alcohols in high optical purities. Thus, this
procedure also provided a convenient method for achiev-
ing the synthesis of secondary alcohols in moderate to
good enantiomeric purities (Scheme 8).
The optical purity of the alcohols thus obtained was
determined by derivatizing with (-)-menthyl chlorofor-
mate26 or (+)-R-methoxy-R-(trifluoromethyl)phenylacetic
acid chloride (MTPA-Cl),27 and the corresponding men-
thyl carbonate and MTPA ester were analyzed on a
capillary GC with respect to their corresponding 1:1
diastereomeric mixtures.
After having achieved only moderate asymmetric
induction (64%) with IpcBH2, it was decided to test the
effectiveness of preformed IpcBHCl‚Et2O reagent in this
reaction. Thus, the preformed IpcBHCl‚Et2O was used
for stepwise hydroboration of trans-1,4-hexadiene as
shown in Scheme 7.
This reaction provided the desired 2-ethylcyclopen-
tanone (22) in 84% ee, a much improved value than
realized with the IpcBH2 reagent. However, the asym-
(27) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34,
2543.

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 63, No. 23, 1998 8281
Ta ble 2. Da ta for th e Op tica lly Active 2-Or ga n ylcyclop en ta n on e Obta in ed via Asym m etr ic Cyclic Hyd r obor a tion of
Su ita ble Dien es w ith Ip cBH2 (2) Rea gen t
dienea
cyclopentanoneb or alcoholb
yield (%)c
% eed
[R]D (c, EtOH)
trans-1,4-hexadiene
22
30
26
32
27
33
28
34
29
35
59
62
50
52
78
75
75
72
80
82
64
45
54
54
60
60
64
64
82
82
-107.5° (1.08)
-2.66° (2.10)
-98.5° (0.81)
-12.45° (0.57)
+1.24° (1.05)
+9.00° (0.50)
-0.96° (1.46)
-8.96° (0.60)
+1.09° (0.55)
+3.09° (0.62)
5-methyl-1,4-hexadiene
2,2-dimethyl-3,6-heptadiene
trans-1-cyclopentyl-1,4-pentadiene
trans-1-phenyl-1,4-pentadiene
a
b
Dienes were prepared by literature procedure29 and purified by fractional distillation. Purified by preparative GC. c Isolated.
d
Determined by resolving diastereomeric MTPA ester or menthyl carbonate derivates on an SPB-5 column.
P r ep a r a tion of Tr a n s-F u sed Bicyclic Keton es fr om
Con clu sion s
Dien es via Asym m etr ic Cyclic Hyd r obor a tion w ith P r e-
for m ed Ip cBHCl‚Et2O.16 The following procedure for the
preparation of (9R,10S)-(+)-trans-1-decalone (7) is representa-
tive. A solution of IpcBH2 (2) (28.5 mL, 20 mmol) in Et2O was
cooled to -10 °C and HCl in Et2O (7.14, 20 mmol) was added
to it dropwise with stirring. After the addition was complete,
the 11B NMR spectrum indicated the formation of a major
amount of IpcBHCl‚Et2O (3).16 In another flask the 1-allyl-
1-cyclohexene (4) (2.68 g, 22 mmol) was dissolved in Et2O (10
mL) and cooled to 0 °C. To it, preformed 3 solution was added
dropwise and the mixture was allowed to stir at 0 °C for 1 h,
when the 11B NMR spectrum indicated major formation of R2-
BCl (9) (δ 74). The reaction mixture was cooled to -20 °C
(ice-water bath), and the LAH (1.0 M, 5 mL, 5 mmol) in Et2O
was added dropwise with stirring. The stirred mixture was
allowed to warm to 24 °C (12 h). The 11B NMR indicated the
formation of clean trialkylborane 5 (δ 81). The mixture was
cooled to 0 °C and acetaldehyde (2.5 mL) added and stirred
for 1 h, when the 11B NMR spectrum indicated the formation
of borinate ester (6) (δ 52). The volatiles were removed by
applying reduced pressure (10 mmHg, 30 min), 6 was dissolved
in Et2O (20 mL), and the solution was cooled to 0 °C. To it
R,R-dichloromethyl methyl ether (30 mmol, 2.70 mL) was
added, followed by the dropwise addition of lithium tert-
butoxide in n-hexanes (40 mmol, generated from tert-butyl
alcohol and n-butyllithium) with stirring. The mixture was
stirred at 0 °C for 1 h and then at 24 °C for 4 h. Water (10
mL) was added, and then the mixture was washed with water
to pH ) 7. Solvent was removed. THF (20 mL) was added
followed by the addition of 3.0 M NaOAc (8.0 mL) and H2O2
(30%, 8.0 mL), and the mixture was stirred at 24 °C for 1 h
and then at 40-50 °C for 1 h. The mixture was diluted with
Et2O (40 mL) and then washed with water (4 × 10 mL), brine
(10 mL), and dried (MgSO4). The solvent was removed and
the residue distilled (64-66 °C, 0.5 mmHg) (lit.10 40 °C., 0.1
mmHg) to afford the desired ketone 7 (2.42 g, 76% yield): Mp
The asymmetric cyclic hydroboration provides a highly
efficient, simple, and promising synthetic route to a
variety of trans-fused polycyclic and cyclic systems.
Thus, the asymmetric cyclic hydroboration of suitable
dienes with the R-pinene-derived chloroborane reagent
(IpcBHCl), obtained by simple operations, followed by the
DCME reaction provide trans-fused bicyclic ketones and
R-substituted-cyclopentanones in high stereo- and enan-
tiomeric purities. Representative bicyclic ketones have
been synthesized by utilizing this methodology, and their
ee can be increased by the upgradation procedures. It
appears that relatively lower asymmetric induction is
achieved in the five-membered ring closure in comparison
with the six-membered ring closure. This methodology
provides convenient access to the 2-organylcyclopen-
tanones in moderate to excellent optical yields. The
intermediate trialkylboranes, obtained in this reaction,
can be conveniently transformed by controlled protonoly-
sis-oxidation into optically active secondary alcohols,
also useful synthons in natural product synthesis.
Exp er im en ta l Section
All glassware was dried at 140 °C overnight, assembled hot,
and cooled to ambient temperature in a stream of nitrogen.28
All reactions involving air- or moisture-sensitive compounds
were performed under a static pressure of dry nitrogen.28
Reported melting points are uncorrected. 11B NMR spectra
were recorded at 96 MHz and were referenced relative to BF3‚
Et2O. 1H and 13C NMR spectra for all new compounds were
recorded at 200 MHz (also on 300 MHz) and 50 MHz,
respectively, relative to internal tetramethylsilane (TMS).
1
Chemical shifts in the H and 13C NMR spectra are reported
38 °C; [R]23 ) +8.20° (c 0.55, EtOH); (lit.11 -10 ( 1°; c 0.5,
D
as parts per million (ppm) downfield from TMS. Optical
rotations were measured on a digital polarimeter in a 1-dm
cell. Preparative HPLC was used to prepare analytical
samples using a C-18 column. The mobile phase used was
acetonitrile with detection at 210 nm. Capillary GC analyses
were performed using the SPB-5 column (30 m).
Ma ter ia ls. Tetrahydrofuran (THF) was distilled from
sodium benzophenone ketyl and used as required. Anhydrous
Et2O, (-)-menthyl chloroformate, 1,4-penta- and hexadienes
and (2S,3S)-(+)-2,3-butanediol were used as such without any
further purification. Certain cyclic and acyclic dienes used in
this study were prepared according to literature procedures
and purified by fractional distillation.29
EtOH).
The same procedure was applied for the synthesis of trans-
fused bicyclic ketones (15-19) from their corresponding dienes.
The results of these reactions are presented in Table 1.
Similarly, by the same procedure 2-organylcyclopentanones
(22, 25-29) were prepared in 53-80% yields. All these
reactions were performed on 10-15 mmol scales. All these
results are summarized in Tables 2 and 3.
Asymmetric cyclic hydroboration of diene 4 and trans-1,4-
hexadiene was performed with IpcBH2 (2) on 10-15 mmol
scale. The reaction was performed at -20 °C for 18 h to
provide the trialkylborane 5 (Scheme 1) and 20 (Scheme 6).
The usual workup procedure as described earlier provided (+)-
trans-1-decalone (7) and 2-ethylcyclopentanone (22) in 50-
69% and 59% yields, respectively. The optical purity (54% ee
for 7 and 64% for 22) of these ketones was determined as
discussed in the later section.
(28) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Syntheses Via Boranes; Wiley-Interscience: New York, 1975.
A reprinted edition, Vol. 1, Aldrich Chemical Co., Inc., Milwaukee, WI,
1997, is currently available.
(29) (a) Gream, G. E.; Serelis, A. K.; Stoneman, T. I. Aust. J . Chem.
1974, 27, 1711. (b) Brown, H. C.; Campbell, J . B., J r. J . Org. Chem.
1980, 45, 549.
Gen er a l P r oced u r e for Up gr a d a tion via Kin etic Reso-
lu tion . The following procedure for the upgradation of (9R,-
10S)-(+)-trans-decalone (7) from 84% ee to >99% ee is repre-

8282 J . Org. Chem., Vol. 63, No. 23, 1998
Dhokte et al.
Ta ble 3. Da ta for th e Op tica lly Active 2-Or ga n ylcyclop en ta n on es Obta in ed via Asym m etr ic Cyclic Hyd r obor a tion of
Su ita ble Dien es w ith Ip cBHCl‚Et2O (3) Rea gen t
dienea
cyclopentanoneb or alcoholb
yield (%)c
% eed
[R]D (c, EtOH)
trans-1,4-hexadiene
22
30
26
32
27
33
28
34
29
35
55
54
53
52
74
70
75
70
78
80
84
84
70
54
77
77
83
83
83
83
-137.5° (0.24)
-3.40° (3.03)
-126.3° (1.05)
-12.45° (0.34)
+1.5° (0.65)
+11.4° (1.23)
-1.20° (1.24)
-11.60° (0.43)
+1.40° (0.63)
+4.20° (0.57)
5-methyl-1,4-hexadiene
2,2-dimethyl-3,6-heptadiene
trans-1-cyclopentyl-1,4-pentadiene
trans-1-phenyl-1,4-pentadiene
a
b
Dienes were prepared by literature procedure29 and purified by fractional distillation. Purified by preparative GC. c Isolated.
d
Determined by resolving diastereomeric MTPA ester or menthyl carbonate derivates on an SPB-5 column.
sentative. A solution of diastereomeric trialkylborane (5) (5
mmol) in Et2O (10 mL) was cooled to 0 °C, benzaldehyde (3.5
mmol, 0.35 mL) was added to it dropwise, and the mixture
was stirred for 6 h. 11B NMR indicated the formation of borinic
ester (11) and the unreacted trialkylborane (5). The mixture
was subjected to the DCME reaction, followed by oxidative
workup as described earlier, provided the desired (+)-trans-
1-decalone (7) (0.5 g, 65% yield) (Scheme 3); Mp 43 °C (lit.11
at 0 °C, and the mixture was stirred for 30 min; 11B NMR
indicated the formation of borinate ester 6 (δ 52). Volatiles
were removed by applying aspirator vacuum. The borinate
ester 6 was dissolved in Et2O (10 mL), and the clear Et2O
solution containing the borinate ester was transferred into
another flask and cooled to 0 °C. The DCME reaction and
oxidative workup as described earlier provided the required
(+)-trans-1-decalone (7) (1.13 g, 74% yield) and a small amount
of crude material further purified by preparative GC: Mp
43 °C); [R]23 ) +10° (c 0.57, EtOH) corresponding to the
D
product of g99% ee.
41-2 °C; [R]23 +10.2 (c 0.53, EtOH).
D
Up gr a d a tion via Ch ela te F or m a tion . The following
procedure for the upgradation of (9R,10S)-(+)-trans-1-decalone
(7) from 84% ee to g99% ee is representative. The borinate
ester (6) was distilled (60-62 °C, 0.5 mmHg). To a solution
of distilled 6 (5 mmol) in Et2O (20 mL) was added (S)-(+)-2-
pyrrolidinemethanol (12) (5 mmol, 0.49 mL) dropwise with
stirring at 24 °C. A white precipitate appeared instantly. The
mixture was allowed to stir at 24 °C for 12 h. It was then
centrifuged and the supernatant layer removed. The solid was
washed with ether (3 × 5 mL) using centrifugation technique.
NMR (CDCl3) δ 5.7; 1H NMR (CDCl3 + DMSO-d6) δ 5.32-
5.52 (m, 1H), 3.9-4.02 (t, 1H), 3.5-3.8 (m, 1H), 3.35-3.48 (t,
1H), 2.97-3.10 (m, 2H), 2.1-0.5 (m, 20H); MS m/z 236 (M +
H), 100). Anal. Calcd for C14H26BNO: C, 71.48; H, 11.06; B,
4.68; N, 5.95. Found: C, 71.59; H, 11.30; B, 4.34; N, 5.72. The
amine complex (13) was then dissolved in Et2O (5 mL), and
HCl in Et2O (5 mmol, 2.1 mL) was added to it to precipitate
2-pyrrolidinemethanol hydrochloride as a yellow gummy solid.
The supernatant layer was transferred into another flask using
a double-ended needle, and the solvent was removed under
vacuum to provide the borinic acid. This acid was dissolved
in n-pentane, MeOH (5 mL) was added, and the mixture was
stirred over molecular sieves (4 Å, beads, 4-8 mesh) for 3 h.
The solvent was removed under vacuum to obtain the borinate
ester (14), which was subjected to the DCME-oxidation reac-
tion as described earlier to provide the desired trans-1-decalone
(7) (0.39 g, 51% yield): Mp 42-43; [R]23D ) +10° (c 0.53, EtOH)
corresponding to a product of g99% ee.
Hyd r obor a tion of 1-Allylcycloh exen e w ith in Situ
Gen er a ted Ip cBHCl‚Et2O. The typical procedure for in situ
generated IpcBHCl‚Et2O, obtained from the reduction of
IpcBCl2 with Me3SiH in Et2O, and its hydroboration with
1-allyl-1-cyclohexene follows. Neat IpcBCl2 (2.19 g, 10 mmol)
was placed in a flask and cooled to -5 °C, and cold (0 °C) Et2O
(9.0 mL) was added. To this resulting IpcBCl2‚Et2O in
solution, diene 4 (1.34 g, 11 mmol) was added, followed by
liquid trimethylsilane (0.74 g, 10 mmol, collected as a liquid
at -78 °C28). The reaction mixture was stirred for 10 min and
brought to ambient temperature. 11B NMR showed the
formation of dialkylchloroborane (9) (δ 76-77) exclusively.
Volatiles of the reaction mixture were removed by applying
aspirator vacuum, dry Et2O (9 mL) was introduced in the flask,
and the solution was cooled to -25 °C. LAH in Et2O (1.0 M,
2.5 mL) was added slowly from the side of the flask. The
reaction mixture was stirred for 4 h and warmed to ambient
temperature; the 11B NMR showed the clean formation of
trialkylborane 5 (δ 84). Acetaldehyde (20 mmol) was added
This procedure provided a significantly improved optical
yield of 81% for the bicyclic ketone 15 while ketone 17 was
obtained in 72% ee. This value is comparable with that (76%
ee) realized with preformed IpcBHCl‚Et2O.
(8R,9S)-(-)-tr a n s-P er h yd r o-4-in d a n on e (15): Yield 67%
for 69% ee compound and 55% for 79% ee (after upgradation
procedure) compound; bp 61-63 °C (1.0 mmHg) (lit.4b 45 °C,
0.5 mmHg); [R]23D ) -7.6° (c 1.09, CHCl3) for 69% ee and [R]23
D
) -8.6° (c 1.01, CHCl3) for 79% ee; IR (neat) 1708 cm-1; H
1
NMR (CDCl3) δ 1.16-2.42 (m, 14H); 13C NMR (CDCl3) δ
212.51, 58.29, 49.89, 41.66, 32.30, 30.95, 28.08, 22.65, 21.99;
MS m/z 139 (M+ + H); HRMS calcd for C9H14O 138.1045, found
138.1046.
The crystalline adduct (13) was isolated: Mp 206-207 °C; 11
B
(10R ,11S )-(+)-t r a n s-P e r h yd r o-1-b e n zoc yc loh e p t a -
n on e (16): Yield 69% of 76% ee compound and 53% of 92% ee
(after upgradation) compound; bp 80-82 °C (1.0 mmHg) (lit.4b
70-72, 0.6 mmHg); [R]23 ) +15.2° (c 1.3, CHCl3) for 76% ee
D
and [R]23 ) +18.5° (c 1.46, CHCl3) for 79% ee; IR (neat) 1708
D
cm-1; 1H NMR (CDCl3) δ 1.30-2.42 (m, 18H); 13C NMR (CDCl3)
δ 214.07, 58.21, 47.34, 41.58, 35.82, 34.85, 28.36, 26.54, 25.79,
25.52, 25.47; MS m/z 167 (M+ + H, 100); HRMS calcd for
C
11H18O 166.1358, found 166.1356.
(11R,10S)-(+)-tr a n s-P er h yd r o-1-b en zocyclooct a n on e
(17): Yield 62% of 76% ee compound and 49% of 90% ee (after
upgradation); bp 100-102 °C (0.6 mmHg); [R]23 ) +5.9° (c
D
1.13, EtOH) for 76% ee and [R]23 ) +7.4° (c 0.84, EtOH) for
D
90% ee compound; IR (neat) 1708 cm-1
;
1H NMR (CDCl3) δ
0.84-2.66 (m, 20H); 13C NMR (CDCl3) δ 213.63, 55.53, 44.53,
42.08, 33.93, 32.67, 27.52, 27.11, 26.77, 26.63, 25.13, 24.16;
MS m/z 180 (M+, 12.1). Anal. Calcd for C12H20O: C, 80.0; H,
11.11. Found: C, 80.01; H, 11.35.
(8R,9S)-(+)-tr a n s-P er h yd r o-1-in d a n on e (18): Yield 66%;
bp 44-45 °C (0.4 mmHg) (lit.4b 43 °C, 0.5 mmHg); [R]23
)
D
+112° (c 1.64, CHCl3); IR (neat) 1738 cm-1; H NMR (CDCl3)
1
δ 0.97-2.43 (m, 14H); 13C NMR (CDCl3) δ 219.34, 56.95, 43.60,
37.30, 32.89, 27.91, 26.10, 25.85, 25.23; MS m/z 139 (M+
+
H), 100; HRMS calcd for C9H14O 138.1045, found 138.1044.
(9R,10S)-(+)-tr a n s-P er h yd r o-1-a zu len on e (19): Yield
66%; bp 66-68 °C (0.2 mmHg) (lit. 68 °C, 0.2 mmHg); [R]23
D
) +78.2° (c 0.77, CHCl3); IR (neat) 1738 cm-1; 1H NMR (CDCl3)
δ 0.80-2.60 (m, 16H); 13C NMR (CDCl3) δ 222.46, 55.69, 43.94,
38.38, 35.70, 29.08, 28.46, 27.86, 27.86, 27.27, 27.00; MS m/z
153 (M+ + H); HRMS calcd for C10H16O 152.1201, found
152.1199.
Gen er a l P r oced u r e for Deter m in in g th e Ee of Bicyclic
Keton es (7, 15-17) via Keta l F or m a tion . The ketone (0.1
mmol) was dissolved in methylene chloride (0.5 mL) and cooled
to -10 °C. (2S,3S)-(+)-2,3-butanediol (0.3 mmol) and chlo-

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 63, No. 23, 1998 8283
rotrimethylsilane (0.6 mmol) were added sequentially. The
reaction mixture was stirred at -10 °C for 0.5 h, poured into
saturated NaHCO3 solution, and extracted with Et2O. The
ethereal solution was dried over MgSO4, filtered, and analyzed
directly on capillary GC on an SPB-5 column (30 m).
NMR, IR, and GC analyses in comparison with their authentic
samples: Bp 119-120 °C (lit.34 116-120 °C); [R]23 ) -6.50°
D
1
(c 0.87, EtOH); (lit.34 -16.1°); IR (neat) 3500 cm-1; H NMR
(CDCl3) δ 0.90 (t, 3H), 1.20 (d, 3 H), 1.30-1.50 (m, 4 H), 3.70-
3.90 (m, 1 H); 13C NMR (CDCl3) δ 14.2, 19.1, 23.4, 41.7, 67.8;
MS m/z 88 (M+).
(-)-2-Eth ylcyclop en ta n on e (22): Yield 59%; bp 90-92 °C
(100 mmHg) (lit.30 92, 100 mmHg); [R]23 ) -137.5° (c 0.24,
(-)-3-Hexa n ol (30): Yield 56%; bp 134-135 °C (lit.35 133-
134 °C); [R]23D ) -3.40° (c 3.03, EtOH) (lit.35 -7.13°); IR (neat)
3345 cm-1; 1H NMR (CDCl3) δ 3.50 (s, 1H), 1.25-1.75 (m, 7H),
0.85-1.50 (m, 6H). The optical yield of 64% was determined
by converting this alcohol into its MTPA ester27 and analyzing
it on an SPB-5 column (30 m).
D
EtOH); IR (neat) 1731 cm-1; 1H NMR (CDCl3) δ 1.92-2.4 (m,
5H), 1.68-1.90 (m, 2H), 1.46-1.64 (m, 1H), 1.20-1.40 (m, 1H),
0.95 (t, J ) 3 Hz, 3H); 13C NMR (CDCl3) δ 50.6, 38.3, 29.0,
22.7, 20.7, 11.9. Anal. Calcd for C7H12O: C, 75.0; H, 10.75.
Found: C, 74.69; H, 11.06. The optical yield of 80% was
determined by analyzing this ketone on Chiraldex GTA (23
m) column at 61 °C (isothermal).
(-)-2-Meth yl-3-h exa n ol (32): Yield 42%; bp 145-146 °C
(lit.36 145-146 °C); [R]23 ) -16.8° (c 0.34, EtOH) (lit.36
D
(-)-2-Meth ylcyclop en ta n on e (25): Yield 42%; bp 137-
+21.25°); IR (neat) 3345 cm-1; 1H NMR (CDCl3) δ 3.40 (s, 1H),
1.20-1.75 (m, 6H), 0.85-1.00 (m, 9H). The optical yield of
54% was determined by converting this alcohol into its
menthyl carbonate26 and analyzing it on an SPB-5 column (30
m).
138 °C (760 mmHg); [R]23D ) -57.9° (c 1.19, CHCl3) [lit.31 [R]23
D
) -110.5° (c 1.19, CHCl3)]; IR (neat) 1731 cm-1
;
1H NMR
(CDCl3) δ 1.94-2.38 (m, 5H), 1.70-1.90 (m, 1H), 1.40-1.58
(m, 1H), 1.08 (dd, J ) 6 Hz, 3H). This ketone was also
obtained by asymmetric cyclic hydroboration of 1,4-pentadiene
with in situ generated IpcBHCl as described earlier. Thus,
optical yield of 51% was obtained for the ketone 25 and was
determined by analyzing this ketone directly on a chiral
column, Chiraldex GTA (23 m) column at 49 °C (isothermal),
in comparison with its 1:1 racemic mixture.
(+)-2,2-Dim eth yl-4-h ep ta n ol (33): Yield 75%; bp 47-49
°C (5 mmHg) [lit.37 46.5 °C (5 mmHg)]; [R]23D ) +11.38° (c 1.23,
EtOH); IR (neat) 3352 cm-1; 1H NMR (CDCl3) δ 1.10-1.50 (m,
7H), 0.90-1.00 (m, 12H); 13C NMR (CDCl3) δ 69.6, 51.5, 42.0,
30.4, 30.3, 29.8, 23.8, 18.9, 14.1. Anal. Calcd for C9H20O: C,
75.0; H, 13.89. Found: C, 74.62; H, 14.22. The optical yield
of 77% was determined by converting this alcohol into its
MTPA ester27 and analyzing it on an SPB-5 column (30 m).
(-)-2-Isop r op ylcyclop en ta n on e (26): Yield 50%; bp 174
°C (760 mmHg) [lit.32 174 °C (760 mmHg)]; [R]23 ) -126.3°
D
(c 1.05, EtOH); IR (neat) 1731 cm-1; 1H NMR (CDCl3) δ 1.90-
2.38 (m, 6H), 1.58-1.80 (m, 2H), 1.00 (d, J ) 6 Hz, 3H), 0.80
(d, J ) 6 Hz, 3H); 13C NMR (CDCl3) δ 222, 55.4, 39.5, 27.6,
24.8, 21.3, 20.8, 18.5.
(-)-1-Cyclop en tyl-2-p en ta n ol (34): Yield 72%; bp 120 °C
(17 mmHg); [R]23 ) -11.6° (c 0.43, EtOH); IR (neat) 3345
D
cm-1; 1H NMR (CDCl3) δ 1.00-2.00 (m, 16H), 0.90 (t, 3H); 13
C
NMR (CDCl3) δ 71.4, 44.2, 40.4, 37.0, 33.5, 32.8, 25.3, 25.2,
19.0, 14.3; HRMS calcd 155.1436, found 155.1435. The optical
yield of 83% was determined by converting this alcohol into
its menthyl carbonate26 and analyzing it on an SPB-5 column
(30 m).
(+)-2-Neop en tylcyclop en ta n on e (27): Yield 78%; bp 130
°C (20 mmHg); [R]23 ) +1.50° (c 0.65, EtOH); IR (neat) 1738
D
cm-1
;
1H NMR (CDCl3) δ 1.65-2.45 (m, 8H), 1.40-1.60 (m,
1H), 0.90 (s, 9H); 13C NMR (CDCl3) δ 222.8, 76.9, 47.1, 44.4,
37.7, 33.0, 30.7, 30.0, 29.9, 21.0.
(+)-P h en yl-2-p en ta n ol (35): Yield 82%; bp 125-127 °C (15
(-)-2-(Cyclop en tylm eth yl)cyclop en ta n on e (28): Yield
mmHg) [lit.38 127 °C (15 mmHg)]; [R]23 ) +4.21° (c 0.57,
75%; bp 78-80 °C (0.5 mmHg) [lit.33 78 °C (0.5 mmHg)]; [R]23
D
D
EtOH); IR (neat) 3385 cm-1; 1H NMR (CDCl3) δ 7.15-7.40 (m,
5H), 3.80 (s, 1H), 2.80 (d, J ) 6 Hz, 1H), 2.65 (q, J ) 6 Hz,
1H), 1.30-1.70 (m, 5H), 0.90 (t, 3H); 13C NMR (CDCl3) δ 138.9,
129.7, 128.8, 128.7, 126.7, 126.2, 72.7, 44.4, 39.3, 19.3, 14.4.
Anal. Calcd for C11H16O: C, 80.49; H, 9.76. Found: C, 80.26;
H, 9.51. The optical yield of 82% was determined by convert-
ing this alcohol into its menthyl carbonate26 and analyzing it
on an SPB-5 column (30 m).
) -1.20° (c 1.24, EtOH); IR (neat) 1735 cm-1; 1H NMR (CDCl3)
δ 1.00-2.40 (m, 18H); 13C NMR (CDCl3) δ 48.7, 38.4, 38.0, 36.0,
33.3, 32.0, 30.1, 25.2, 25.0, 20.8. Anal. Calcd for C11H18O: C,
79.52; H, 10.84. Found: C, 79.17; H, 11.11.
(+)-2-Ben zylcyclop en t a n on e (29): Yield 80%; bp 109-
111 °C; [R]23 ) +1.40° (c 0.63, EtOH); IR (neat) 1731 cm-1
;
D
1H NMR (CDCl3) δ 7.10-7.50 (m, 5H), 3.15 (dd, J ) 4 Hz, and
J ) 2 Hz, 1H), 2.55 (q, J ) 3 Hz, 1H), 2.25-2.46 (m, 2H), 1.88-
2.20 (m, 3H), 1.45-1.85 (m, 2H); 13C NMR (CDCl3) δ 140.3,
129.2, 129.0, 128.7, 128.6, 126.5, 76.7, 51.3, 38.5, 35.9, 29.4,
20.8. Anal. Calcd for C12H14O: C, 82.75; H, 8.06. Found: C,
82.39; H, 8.11.
Ack n ow led gm en t. This work was initiated with
support from the National Institutes of Health (Grant
GM 10937) and completed with support from the Borane
Research Fund.
Gen er a l P r oced u r e for th e Syn th esis of Ch ir a l Alco-
h ols. The following procedure for the synthesis of optically
active (-)-2-pentanol (31) is representative. The reaction was
performed on a 10 mmol scale. To the trialkylborane, formed
from the reaction of preformed IpcBHCl‚Et2O with 1,4-pen-
tadiene as described earlier, glacial acetic acid (10 mL) was
added, and it was stirred at 24 °C for 10 min. The excess of
acetic acid was neutralized with aqueous 3 M NaOH, and
NaOH (3.0 M, 4 mL) was added followed by the addition of
30% H2O2 (4 mL) and the usual work up providing 1- and the
desired 2-pentanol in 30:70 ratio in 48% yield. These alcohols
were separated by preparative GC and characterized by 1H
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 7, 13, 15-19, 22, and 26-35 and 13C NMR spectra
for compounds 7, 13, 15-19, 26-29, and 33-35 (39 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
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J O981040C
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