Diastereo- and enantioselective synthesis of syn-α-vinylchlorohydrins and cis-vinylepoxides

Article abstract of DOI:10.1021/jo960875p

A new method to generate chiral syn-vinylchlorohydrins and cis-vinyloxiranes is reported. Reaction of (α-haloallyl)lithiums with methoxy-9-BBN or Ipc₂BOMe followed by treatment with BF₃·OEt₂ leads to (Z)-(γ-haloallyl)boranes which react with aldehydes to yield cis-vinylepoxides (de ≥ 90%) upon oxidative workup. Alternatively, addition of ethanolamine to the allylboration product yields syn-α-halohydrins (de ≥ 90%) that are also easily cyclized to cis-vinylepoxides. Extension of this protocol using [(Z)-γ-chloroallyl]BIpc₂ leads to chiral syn-α-chlorohydrins and cis-vinylepoxides in high de (≥90%) and ee (90-99%). Enantioselectivity of reactions of chiral (Z)-(γ-chloroallyl)boranes with aldehydes are more sensitive to reaction conditions than enantioselectivity of reactions of other α-or γ-substituted allylboranes. The effects of proportion of BP₃·OEt₂ and the relative efficacies of LiNR₂ bases on diastereo- and enantioselectivity of the chloroallylation are reported.

Full text of DOI:10.1021/jo960875p

J . Org. Chem. 1996, 61, 7513-7520
7513
Dia ster eo- a n d En a n tioselective Syn th esis of
syn -r-Vin ylch lor oh yd r in s a n d cis-Vin ylep oxid es
Shaojing Hu, Seetharaman J ayaraman,* and Allan C. Oehlschlager*
Department of Chemistry, Simon Fraser University, Burnaby, B.C, Canada, V5A 1S6
Received May 14, 1996X
A new method to generate chiral syn-vinylchlorohydrins and cis-vinyloxiranes is reported. Reaction
of (R-haloallyl)lithiums with methoxy-9-BBN or Ipc2BOMe followed by treatment with BF3‚OEt2
leads to (Z)-(γ-haloallyl)boranes which react with aldehydes to yield cis-vinylepoxides (de g 90%)
upon oxidative workup. Alternatively, addition of ethanolamine to the allylboration product yields
syn-R-halohydrins (de g 90%) that are also easily cyclized to cis-vinylepoxides. Extension of this
protocol using [(Z)-γ-chloroallyl]BIpc2 leads to chiral syn-R-chlorohydrins and cis-vinylepoxides in
high de (g90%) and ee (90-99%). Enantioselectivity of reactions of chiral (Z)-(γ-chloroallyl)boranes
with aldehydes are more sensitive to reaction conditions than enantioselectivity of reactions of
other R-or γ-substituted allylboranes. The effects of proportion of BF3‚OEt2 and the relative efficacies
of LiNR2 bases on diastereo- and enantioselectivity of the chloroallylation are reported.
Sch em e 1. Allylbor a tion Em p loyin g r- a n d
γ-Su bstitu ted Allylic Bor on Com p ou n d s
In tr od u ction
Addition of allyl organometallic reagents to carbonyl
compounds is an important method for the stereocon-
trolled formation of carbon-carbon bonds,1 and allylic
organoboranes are particularly versatile members of this
class of reagents (Scheme 1).2-6
We have applied the allylboration of aldehydes to the
preparation of syn-R-halohydrins and cis-vinylepoxides
(Scheme 2). When boron possesses chiral ligands, the
reaction sequence is enantioselective. The present route
to syn-chlorohydrins7 is superior to other methods such
as asymmetric reduction of R-halo-substituted ketones8
and opening of chiral epoxides.7a Under our allylboration
conditions, syn-R-halohydrins are easily converted to
vinyloxiranes.9-13 The primary advantage of the new
methodology is in the ease of preparation of chiral cis-
vinyloxiranes which are obtainable only via Sharpless
epoxidation of (Z)-allylic alcohols. Although Sharpless
epoxidation proceeds with high enantioselectivity with
(E)-allylic alcohols it gives variable enantioselectivity
with the (Z)-isomers.14
Sch em e 2
Resu lts a n d Discu ssion
X Abstract published in Advance ACS Abstracts, September 15, 1996.
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(2) (a) Roush, W. R. In Comprehensive Organic Synthesis; Heath-
cock, C. H., Ed.; Pergamon Press: Oxford, 1991; Vol. 2, pp 1-53. (b)
Barrett, A. G. M.; Malecha, J . W. J . Chem. Soc., Perkin Trans. 1 1994,
1901. (c) Barrett, A. G. M., Seefeld, M. A.; Williams, D. J . J . Chem.
Soc., Chem. Commun. 1994, 1053. (d) Barrett, A. G. M., Seedfeld, M.
A. Tetrahedron 1993, 49, 7857.
(3) Hoffmann, R. W. Pure Appl. Chem. 1988, 60, 123.
(4) Brown, H. C.; J adhav, P. K.; Bhat, K. S. J . Am. Chem. Soc. 1988,
110, 1535.
(5) (a) Hunt, J . A.; Roush, W. R. Tetrahedron Lett. 1995, 36, 501.
(b) Roush, W. R.; Grover, P. T. Tetrahedron 1992, 48, 1981. Also, see
ref 2.
(6) (a) Ager, D. J .; East, M. B. Tetrahedron, 1992, 48, 2803. (b)
Hoffmann, R. W.; Munster, I. Tetrahedron Lett. 1995, 36, 1434.
(7) (a) Bonini, C.; Righi, G. Synthesis 1994, 225. (b) Wright, A. D.;
Konig, G. M.; de Nys, R.; Sticher, O. J . Nat. Prod. 1993, 56, 394.
(8) (a) Corey, E. J .; Bakshi, R. K.; Shibata, S.; Chen, C. P.; Singh,
V. K. J . Am. Chem. Soc. 1987, 109, 7925. (b) Corey, E. J .; Helal, C. J .
Tetrahedron Lett. 1993, 34, 5227.
Syn th esis of (Z)-(γ-ch lor oa llyl)bor a n es. Sterically
encumbered trialkylboranes normally react with R-sub-
stituted allyllithiums at the less substituted position to
provide the corresponding γ-substituted allylboron ate
complex.15 By contrast, (R-chloroallyl)lithium, generated
in situ from allyl chloride and LDA, reacts with borate
esters to produce ate complexes which yield (R-chloroal-
lyl)boronate esters by dealkoxylation.16 The latter react
with aldehydes to yield γ-chlorohydrins. If the borate
reagent contains sterically demanding ligands, reaction
with (R-chloroallyl)lithium leads to (R- and (γ-chloroallyl)-
boronates (Scheme 3).17b Sterically less demanding
9-methoxy-9-BBN reacts with (R-chloroallyl)lithium to
give predominantly the (R-chloroallyl)boron ate com-
plex.18 Regioselectivity in allylborane formation thus
(9) Alexakis, A.; Cahiez, C.; Normant, J . G. F. Tetrahedron Lett.
1978, 19, 2027.
(10) Ley, S. V. Pure Appl. Chem. 1994, 66, 1415.
(11) (a) Heumann, A.; Re´glier, M. Tetrahedron 1995, 51, 975. (b)
Barret, A. G. M.; Sturgess, M. A. Tetrahedron 1988, 44, 5615.
(12) Marshall, J . A. Chem. Rev. 1989, 89, 1503.
(14) J ohnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH Publishers: New York, 1993; pp 103-
158.
(15) Yamamoto, Y.; Yatagai, H.; Saito, Y.; Maruyama, K. J . Org.
Chem. 1984, 49, 1096.
(13) (a) Tsuji, J . Tetrahedron 1986, 42, 4361. (b) Trost, B. M. Angew.
Chem. Int. Ed. Engl. 1995, 34, 259. (c) Trost, B. M.; Sudhakar, A. R.
J . Am. Chem. Soc. 1987, 109, 3792.
(16) (a) Brown, H. C.; Rangaishevi, M. V. Tetrahedron Lett. 1990,
31, 7113. (b) Brown, H. C.; Rangaishevi, M. V. Tetrahedron Lett. 1990,
31, 7115.
S0022-3263(96)00875-4 CCC: $12.00 © 1996 American Chemical Society

7514 J . Org. Chem., Vol. 61, No. 21, 1996
Hu et al.
Sch em e 3
ratio 98:2), but the diastereoselectivity (syn vs anti) is
only 91:9 (Table 2, entry 8). When the entire reaction
sequence is conducted at -95 °C using LiN(c-Hex)2,
regioselectivity increases to the point that no γ-chloro-
hydrin is detectable and the de increases to 98% (Table
2, entries 13-16).
Preparation of (chloroallyl)borane 13a at -95 °C,
followed by warming to room temperature, stirring for 2
h, and recooling to -95 °C for 0.5 h, before reaction at
-95 °C with benzaldehyde (Table 2, entry 12), did not
lower diastereoselectivity. This experiment provides
additional evidence that (γ-chloroallyl)boranes are con-
figurationally stable. Similarly, no decrease in diaste-
reoselectivity is observed when 13a is prepared at -95
°C, warmed to -78 °C, and reacted with PhCHO at the
latter temperature (Table 2, entry 15).
The formation of (Z)-(γ-chloroallyl)boranes may be due
to attack of the boron at the γ-position of (R-chloroallyl)-
lithium or via rearrangment of an initially formed (R-
chloroallyl)borane. Evidence for the formation of (R-
chloroallyl)boranes from (R-chloroallyl)lithiums comes
from the observation that treatment of (R-chloroallyl)-
lithium with methoxy-9-BBN results in a ring-expansion
that is most feasible via an (R-chloroallyl)boron ate
complex.18 It is well known that decomposition of allyl-
boron ate complexes with Lewis acids such as BF3‚OEt2
is accompanied by allylic rearrangement.20 Thus, pre-
cedents exist which suggest that (γ-chloroallyl)boranes
5 could arise from BF3‚OEt2-promoted decomposition of
R-ate complexes 4 with a concomitant [1,3]-boron shift
(Scheme 4). Since previous reports suggest that the [1,3]-
rearrangement of R-methylallyl-9-BBN to (Z)- and (E)-
isomers of crotyl-9-BBN occurs at low temperatures,21 we
appears to be influenced by the steric requirements of
the boron substituents.
We reinvestigated the reaction between (R-chloroallyl)-
lithium and 9-methoxy-9-BBN. At -78 °C BF3‚OEt2-
promoted decomposition of the resultant ate complex 3
produces a mixture of chloroallylboranes 4 and 5 which
upon reaction with aldehydes and treatment with etha-
nolamine19 yields syn-chlorohydrins 7 and γ-chlorohy-
drins 6 in a ratio of 89-85:11-15 (de 84-88%, Scheme
4; Table 1). The inferior diastereoselectivity is attributed
to the formation of minor amounts of (E)-(γ-chloroallyl)-
borane 5c along with major (Z)-γ-isomer 5a . Lowering
the temperature (-95 °C) for the formation and decom-
position of the ate complex improves the regio- and
diastereoselectivities (Table 1). Use of a more sterically
demanding base, lithium dicyclohexylamide [LiN(c-
Hex)2], further improves regioselectivity in favor of the
syn-chlorohydrin 7 and dramatically improves diastereo-
selectivity (de ) 98%) (Table 2, entry 1). Formation of
syn-chlorohydrins 7 requires (Z)-(γ-chloroallyl)borane 5a
whereas 6 is derived from the (R-chloroallyl)borane 4.
Regio- and stereoselectivities of reactions of the reagent
formed from (R-chloroallyl)lithium, 2a , and BF3‚OEt2 are
relatively insensitive to reaction conditions (Table 2,
entries 1-6). Reaction of (R-chloroallyl)lithium with 2a
at -95 °C followed by demethoxylation of the complex
with BF3‚OEt2 at -95 °C and reaction with benzaldehyde
at temperatures between -41 °C and -95 °C consistently
yields syn-chlorohydrin 7 with 99:1 diastereoselectivity,
suggesting 5a is configurationally stable over this tem-
perature range.
1
examined formation of 4 by low temperature H NMR.
In initial experiments we were unable to determine if
both (R- and (γ-chloroallyl)boranes were present. The
driving force for formation of the (Z)-(γ-chloroallyl)borane
may be due to Lewis base behavior of γ-chlorine.
Ha loa llylbor a tion s w ith 13. The (Z)-halo-substitut-
ed allylboranes 13a -d react rapidly with aldehydes at
-95 °C to give halohydrins upon ethanolamine workup,19
and cis-vinyloxiranes after oxidative workup.22 High
diastereo- and enantioselectivities are realized in these
experiments (Scheme 5; Table 3). Routine oxidation
(OH-/H2O2) of the carbon-boron bond22 lowers optical
purities of base-sensitive oxiranes compared to their
halohydrin precursors and is not recommended (Table
3, entries 3, 4, 7, and 8). Such oxiranes are best obtained
by cyclization of corresponding chlorohydrins in a sepa-
rate step. We successfully employed K2CO3/MeOH or
KO-t-Bu/THF to generate base-sensitive oxiranes with
no diminution of optical purity compared to the chloro-
hydrin precursors.
We anticipated that introduction of a bulky chiral
auxiliary would improve regioselectivity and yield chiral
syn-chlorohydrins (Scheme 5). Use of Brown’s chiral
auxiliary, (-)-B-methoxydiisopinocampheylborane (dIpc2-
BOMe, 2b) in the chloroallylboration reaction (-78 °C)
with LDA as base enhances the regioselectivity (13:12,
The absolute configurations of chlorohydrins, 16 [R )
(E)-PhCHdCH, c-Hex] obtained from 2b were deter-
mined by hydrogenolysis to alcohols, 21, of known con-
figuration23 (Scheme 6). The configurations of the hy-
(17) For various methods of synthesis of (() vinylepoxides, see: (a)
Mallaiah, K.; Satyanarayana, J .; Ila, H.; J unjappa, H. Tetrahedron Lett.
1993, 34, 3145. (b) J ulia, M.; Verpeaux, J . N.; Zahneisen, T. Bull. Soc.
Chim. Fr. 1994, 131, 539. (c) Doucoure, A.; Mauze, B.; Miginiac, L. J .
Organomet. Chem. 1982, 236, 139. (d) Hoffmann, R. W.; Kemper, B.
Tetrahedron 1984, 40, 2219. (e) Trost, B. M.; Sudhakar, A. R. J . Am.
Chem. Soc. 1988, 110, 7933. (f) Trost, B. M.; Melvin, L. S. Sulfur ylids.
Emerging Synthetic Intermediates; Academic Press: New York, 1975.
Also, see ref 13c.
(20) (a) Hoffmann, R. W.; Feussner, G.; Zeiss, H. J .; Schulz, S. J .
Organomet. Chem. 1980, 187, 321. (b) Blais, J .; L'Honore´, A.; Soulie´,
J .; Cadiot, P. J . Organomet. Chem. 1974, 78, 323.
(21) (a) Hancock, K. G.; Kramer, J . D. J . Organomet. Chem. 1974,
64, C29. (b) Kramer, G. W.; Brown, H. C. J . Organomet. Chem. 1977,
132, 9.
(22) (a) J adhav, P. K.; Bhat, K S.; Perumal, P. T.; Brown, H. C. J .
Org. Chem. 1986, 51, 432. (b) Racherla, U. S.; Brown, H. C. J . Org.
Chem. 1991, 56, 401.
(18) Brown, H. C.; J ayaraman, S. J . Org. Chem. 1993, 58, 6791.
(19) Brown, H. C.; Racherla, U.; Liao, Y.; Khanna, V. V. J . Org.
Chem. 1992, 57, 6608.
(23) J acques, J .; Gros, G.; Bourcier, S. In Stereochemistry; Kagan,
H. B, Ed.; G. Thieme, Stuttgart, 1977; Vol 4.

Synthesis of syn-R-Vinylchlorohydrins and cis-Vinylepoxides
Sch em e 4
J . Org. Chem., Vol. 61, No. 21, 1996 7515
Ta ble 1. Rea ction of (Ch lor oa llyl)bor a n es 4 a n d 5 w ith
Ald eh yd es a t Low Tem p er a tu r esa
substituted at the γ-position with electron-donating
groups since the former are less nucleophilic at the
reacting allyl carbon. Thus, although high stereoselec-
tion is observed for reactions of (γ-haloallyl)boranes it
would be expected to be much more sensitive to temper-
ature and solvent than allylborations with more electron-
rich analogs.
In agreement with these expectations reaction of (γ-
chloroallyl)borane 13a with benzaldehyde at -78 °C
generates syn-chlorohydrin of 78% ee. Lowering the
temperature to -95 °C improves the ee to 97% (Table 3,
entry 3).
To test the influence of solvent(s) on the enantioselec-
tivity, we added LiN(c-Hex)2 in THF to a mixture of Ipc2-
BOMe and allyl chloride in diethyl ether at -95 °C.
Addition of benzaldehyde followed by workup gives
R-chlorohydrin of 97% ee. When the same reaction is
conducted using only THF, the ee is lowered to 75%
(Table 3, entry 4). In contrast, allylborations with
unsubstituted allyl- and (Z)-(γ-alkoxyallyl)boranes pro-
ceed with high enantioselectivity which is independent
of solvent and is maximum at -78 °C in THF.25b
Reaction of benzaldehyde with (Z)-(γ-bromoallyl)bo-
ranes 13b, d , prepared by in situ deprotonation of allyl
bromide, generated R-bromohydrins with syn selectivity
of 90:10 when benzaldehyde was added at -78 °C (Table
2, entry 9). The (R/γ-bromoallyl)borane reagent was less
regio- and diastereoselective than the analogous (R/γ-
chloroallyl)boranes (Table 2, entries 10 and 11). Lower
diastereoselectivity is attributed to steric conjestion and
lower Lewis base character of the (Z)-γ-bromine which
increases the proportion of (E)-isomer.
chlorohydrinb
vinyloxirane 9c
yield
(%)d
R vs γ
7+8:6
yield
cis vs
entry
1
R′CHO R′ )
(%)d,e
transf
1
2
3
1a
1a
1b
1b
1a
1a
Ph
PhCH2
Ph
c-Hex
Ph
c-Hex
79
86
76
78
77
76
85:15
87:13
88:12
89:11
91:9
95
97
96
97
98
98
92:8
94:6
94:6
93:7
95:5
94:6
4
5g
6g
95:5
a
Unless noted reactions were carried out at -78 °C, using 1.2
b
equiv of LDA and 2.6 equiv of BF3‚OEt2. Ratios determined by
product isolation. c Obtained by direct oxidative workup or cy-
clization of 7 and 8. Isolated yields. e Yields of chlorohydrin
d
cyclization. f Ratios determined by 1H NMR and capillary GC
analyses. Capillary GC analyses of chlorohydrins (syn vs anti)
g
gave the same ratio. Reactions carried out at -95 °C.
drogenation products 21 (R1 ) PhCH2CH2, c-Hex) were
d
further established by synthesis from Ipc2B(allyl). The
absolute configurations of other halohydrins and viny-
loxiranes resulting from γ-haloallylborations using 2b
and 2c were assigned by analogy with these two correla-
tions.
The enantiopreferences of γ-haloallylborations using
2b and 2c are consistent with those for allylboration
reagents derived from (+)- and (-)-R-pinene, respectively
(Table 3).24 The enantiopreference observed for (γ-
d
haloallyl)boranes derived from Ipc2BOMe involves si face
attack, which is in agreement with previous reports,22a,24
for related reagents (Scheme 7).
Allylborations proceed via initial rapid formation of a
carbonyl-boron ate complex and rate-determining for-
mation of a new carbon-carbon bond via a cyclic six-
membered chair transition state. Stereocontrol is mani-
fested during the formation of the new carbon-carbon
bond (Scheme 7). Transition states25a for this process are
expected to be earlier for (γ-haloallyl)borane analogs
compared to unsubstituted allylboranes or allylboranes
Effect of Stoich iom etr y of BF 3‚OEt2. Decomposi-
tion of allylboron ate complexes usually requires excess
BF3‚OEt2.26 Treatment of ate complexes 10, 11 with 1.33
equiv of BF3‚OEt2 followed by immediate condensation
with aldehydes generates mixtures of chlorohydrin and
(25) (a) For transition state energy calculations, see: Vulpetti, A.;
Gardner, M.; Gennari.; Bernardi, A.; Goodman, J . M.; Paterson, I. J .
Org. Chem. 1993, 58, 1711. (b) Brown, H. C.; Racherla, U. S.; Pellechia,
P. J . J . Org. Chem. 1990, 55, 1868.
(24) (a) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.;
Racherla, U. S. J . Am. Chem. Soc. 1990, 112, 2389. (b) Brown, H. C.;
Bhat, K. S.; J adhav, P. K. J . Chem. Soc., Perkin Trans. 1 1991, 2633.
(26) Brown, H. C.; Sinclair, J . J . Organomet. Chem. 1977, 131, 163.

7516 J . Org. Chem., Vol. 61, No. 21, 1996
Ta ble 2. Ha loa llylbor a tion of Ben za ld eh yd e u n d er Differ en t Con d ition sa
Hu et al.
temp1
(°C)b
temp2
(°C)c
temp3
(°C)d
BF3‚OEt2
(equiv)
halohydrin
epoxide
ee, %
entry
X
2
R:γe
cis:trans f
(cis) g
1
2h
3
4
5
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Cl
Br
Cl
Cl
Cl
Cl
Cl
-95
-95
-95
-95
-95
-95
-95
-78
-78
-78
-78
-95
-95
-95
-95
-95
-95
-95
-95
-95
-95
-95
-95
-78
-78
-95
-95
-95j
-95
-95
-95
-95
-95
-95
-78
-62
-41
-95
-95
-78
-78
-95
-95
-95
-95
-95
-78
-78
2.63
2.63
1.33
1.33
1.33
1.33
1.5
2.63
2.63
2.63
2.65
2.65
1.33
1.66
2.63
1.33
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
95:5
98:2
99:1
99:1
95:5
99:1
99:1
99:1
99:1
99:1
91:9
90:10
99:1
94:6
99:1
99:1
99:1
99:1
99:1
99:1
>99:<1
>99:<1
96:4
98:2
96:4
6
7
8i
9
78
74
88
86
87
98
97
86
85
10
11
12
13
14
15
16
99:1
98:2
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
a
LiN(c-Hex)2 was used, unless noted. b Temp1, temperature of ate complex formation. c Temp2, temperature of ate complex decomposition
using BF3‚OEt2. Temp3, temperature of R′CHO addition. e Ratios of R vs γ-halohydrins by isolation. Syn vs anti ratios of R-halohydrins
d
by capillary GC analysis. This was same as the cis vs trans ratios of epoxides. Obtained by cyclization of chlorohydrins. Ratios by 1H
f
g
NMR and capillary GC analyses. ee’s by GC (Cyclodex B, 30 m × 0.25 mm i.d. column) analyses of syn-R-halohydrins and epoxides were
h
i
j
identical. Cyclohexanecarboxadehyde was used. LDA was used. After decomposition of ate complex, the reaction was warmed to rt
for 2 h, and then recooled to -95 °C for 0.5 h before addition of aldehyde.
lamine, dicyclohexylamine [(c-Hex)2NH], N-isopropylcyclo-
hexylamine, and 2,2,6,6-tetramethylpiperidine were freshly
distilled from CaH2 prior to use. Allyl chloride was freshly
distilled over P2O5 prior to use. Aldehydes were distilled prior
vinyloxirane (ratio 90:10). The formation of vinyloxirane
may result from the presence of dialkylamine. This
procedure is suitable for BF3‚OEt2-sensitive substrates
and products. Use of 2.6 equiv of BF3‚OEt2 results in
exclusive chlorohydrin formation (Table 2). Although
excess BF3‚OEt2 increases the proportion of γ-chlorohy-
drins, it prevents formation of vinyloxirane by complex-
ation with dialkylamine.
l
to use. The dIpc2BOMe, Ipc2BOMe, and 9-BBN were pur-
chased from Aldrich and used without purificaton. Moisture-
and air-sensitive reactions were conducted under argon in
vacuum-dried glassware. A nitrogen glove-bag was used to
weigh moisture-sensitive compounds. Syringes and cannulas
were used to transfer air-sensitive reagents.28 Unless other-
wise stated, standard workup refers the combination of organic
extracts, washing with ice-cold brine, drying over anhydrous
MgSO4, and concentration in vacuo. 1H NMR and 13C NMR
spectra were recorded at 400 and 100 MHz, respectively. GC
analyses were conducted using a 30-m × 0.25-mm i.d. fused
silica column coated with DB-1 with FID detection.
Reactions of 13 with benzaldehyde are more sensitive
.
to the amount of BF3 OEt2 (Table 4, entries 3-5) than
are reactions with aliphatic aldehydes. For reactions in
which LDA is used as the base, lowering the amount of
BF3‚OEt2 from 2.5 equiv to 1.33 equiv increases the ee
of chlorohydrin from 84% to the maximum obtained in
this work, 95%.
Gen er a l P r oced u r e for Ch lor oa llylbor a tion of Ald e-
h yd es Usin g Ip c2BOMe syn -(1R,2R)-2-Ch lor o-1-cyclo-
h exyl-3-bu ten -1-ol (16a ). To a stirred and cooled (-95 °C)
mixture of dIpc2BOMe (11.5 mmol) and allyl chloride (15 mmol)
in anhyd ether (50 mL) was added a solution of LiN(c-Hex)2
Effect of Str u ctu r e of LiNR2 Ba ses on th e EE of
Ch lor oh yd r in s. LDA, LiN(c-Hex)2, LiTMP, and LiN-
(c-Hex)i-Pr are reported to efficiently metalate allyl
chloride.18 We briefly examined the effect of base on the
enantioselectivity of syn-chlorohydrin formation (Table
5). With the exception of LDA, which gave lower dias-
tereo- and enanatioselectivities, all bases examined gave
chlorohydrin with comparable diastereo- and enantio-
meric composition.
.
(15 mmol) in THF (25 mL). After stirring for 1 h, BF3 OEt2
(30 mmol) was added followed by cyclohexanecarboxaldehyde
(11.5 mmol). The reaction was continued at -95 °C for 4 h.
All solvents were removed in vacuo at rt, and the residue was
triturated with n-pentane (40 mL) and allowed to settle (12
h). The supernatant was transferred to another predried flask
by cannula. The residue was further treated with pentane (2
× 30 mL), and the pentane extracts were combined. Removal
of pentane in vacuo furnished a semisolid. (For direct oxida-
tive workup, see synthesis of cis-vinylepoxides). This residue
was dissolved in ether and treated with ethanolamine follow-
ing the reported procedure.19 Standard workup followed by
flash chromatography (hexane:ether, 95:5) yielded 16a as a
colorless liquid (1.5 g, 72% yield): 13C NMR and 1H NMR
Con clu sion s
In summary, (R-chloroallyl)lithium, generated in situ,
is trapped by 9-MeO-9-BBN. Subsequent treatment with
.
BF3 OEt2 leads to (Z)-(γ-chloroallyl)borane 5, which con-
denses with aldehydes to yield (() syn-R-chlorohydrins
d
l
7 and (() cis-vinyloxiranes 9.27 Use of Ipc2BOMe or -
Ipc2BOMe in this process leads to (Z)-(γ-chloroallyl)-
boranes 13a -d which yield chiral chlorohydrins and cis-
vinyloxiranes in high de and ee. A similiar sequence
using (bromoallyl)lithium provided chiral syn-R-bromo-
hydrins with slightly lower de and ee.
spectral data are in agreement with those reported.17b [R]23
D
+56.68 (c ) 2.41, CHCl3).
syn -(1R,2R)-2-Ch lor o-1-p h en yl-3-bu t en -1-ol (16b ). 1H
NMR and 13C NMR spectral data are in agreement with
reported values.17b [R]23 +18.86 (c ) 1.92, CHCl3).
D
syn -(3R,4R)-3-Ch lor o-1-d od ecen -4-ol (16c). IR (film) ν
3406, 1077, 987, 927 cm-1 1H NMR (CDCl3) δ 5.94 (ddd, J )
.
17.6, 10.2, 8.6 Hz, 1H), 5.36 (ddd, J ) 17.6, 1, 1 Hz, 1H), 5.23
(ddd, J ) 10.2, 1, 1 Hz, 1H), 4.32 (dd, J ) 8.7, 5.6 Hz, 1H),
3.65 (m, 1H), 2.17 (d, J ) 2.0 Hz, 1H), 1.58-0.86 (m, 17H).
13C NMR (CDCl3) δ 135.45, 118.77, 74.27, 68.85, 34.90, 33.80,
Exp er im en ta l Section
Gen er a l Ch em ica l P r oced u r es. THF and diethyl ether
were distilled from sodium-benzophenone ketyl. Diisopropy-
(27) J ayaraman, S.; Hu, S.; Oehlschlager, A. C. Tetrahedron Lett.
1995, 36, 4765.
(28) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Synthesis via Boranes; Wiley-Interscience: New York, 1975.

Synthesis of syn-R-Vinylchlorohydrins and cis-Vinylepoxides
Sch em e 5
J . Org. Chem., Vol. 61, No. 21, 1996 7517
29.50, 29.46, 29.20, 25.52, 22.62, 14.01. CIMS m/ z (isobutane,
rel intensity) 201 [(M+ - 18) + 1 (8.3)], 183 (54.3), 165 (68.9),
125 (29.8), 107 (57.5). [R]23 +14.50 (c ) 2.0, CHCl3). Anal.
Calcd for C8H13ClO: C, 59.81; H, 8.16. Found: C, 59.69; H,
8.20.
D
141 (100). [R]23 +35.18 (c ) 2.08, CHCl3). Anal. Calcd for
D
C12H23ClO: C, 65.88; H, 10.60. Found: C, 65.78; H, 10.39.
syn -(3R,4R)-4-Ch lor o-1-p h en yl-(5E)-1,5-h exa d ien -3-ol
syn -(2R,3R)-3-Ch lor o-1-p h en yl-4-p en ten -2-ol (16d ). IR
(16f). IR (film) ν 3395, 1651, 1494, 1449, 1070, 967, 931 cm-1
.
(film) ν 3416, 1604, 1454, 1085, 989, 932 cm-1
.
1H NMR
1H NMR (CDCl3) δ 7.42-7.23 (m, 5H), 6.71 (d, J ) 15.1 Hz,
1H), 6.21 (dd, J ) 15.1, 6 Hz, 1H), 5.98 (ddd, J ) 16.9, 10.2,
7.8 Hz, 1H), 5.40 (d, J ) 16.9 Hz, 1H), 5.29 (d, J ) 10.2 Hz,
1H), 4.65-4.39 (m, 2H), 2.41 (s, 1H). 13C NMR (CDCl3) δ
136.27, 134.63, 133.12, 128.65, 128.06, 126.99, 126.70, 119.54,
75.20, 67.71. EIMS m/ z (rel intensity) 208 [M+ (4.3)], 172 (21),
133 (100), 115 (26.5), 103 (8.1), 91 (5.5), 77 (12), 55 (12.7).
HRMS Calcd for C12H13ClO: 208.0655. Found: 208.0655.
(CDCl3) δ 7.35-7.23 (m, 5H), 6.03 (ddd, J ) 16.9, 10.2, 7.5
Hz, 1H), 5.37 (ddd, J ) 16.9, 1, 1 Hz, 1H), 5.28 (ddd, J ) 10.2,
1, 1 Hz, 1H), 4.36 (dd, J ) 7.7, 4.6 Hz, 1H), 3.94 (m, 1H), 2.97
(dd, J ) 13.8, 5 Hz, 1H), 2.81 (dd, J ) 13.8, 7.8 Hz, 1H), 2.18
(d, J ) 5.6 Hz, 1H). 13C NMR (CDCl3) δ 137.45, 135.27, 129.43,
126.65, 126.76, 119.08, 75.12, 67.06, 40.31. CIMS m/ z (isobu-
tane, rel intensity) 197 [M+ + 1 (12.7)], 179 (29.8), 161 (27.5),
151 (4.3), 143 (100), 133 (7.3), 121 (36.7). [R]23 +15.7 (c )
D
syn -(3R,4R)-4-Ch lor o-2-m eth yl-5-h exen -3-ol (16g). IR
2.88, CHCl3). Anal. Calcd for C11H13ClO: C, 67.18; H, 6.66.
Found: C, 66.99; H, 6.78.
(film) ν 3363, 1651, 1416, 1087 cm-1 1H NMR (CDCl3) δ 5.97
.
(ddd, J ) 16.9, 10.2, 6.8 Hz, 1H), 5.37 (ddd, J ) 16.9, 1, 1 Hz,
1H), 5.24 (ddd, J ) 10.2, 0.7, 0.7 Hz, 1H), 4.50 (dd, J ) 8.8,
3.6 Hz, 1H), 3.36 (dd, J ) 8.0, 3.6 Hz, 1H), 2.05 (d, J ) 6.2 Hz,
1H), 1.87 (m, 1H), 0.97 (dd, J ) 9.9, 6.8 Hz, 6H). 13C NMR
(CDCl3) δ 135.75, 118.4, 78.90, 67.45, 31.02, 19.67, 16.47.
CIMS m/ z (isobutane, rel intensity) 149 [(M+ + 1 (12.3)], 131
syn -(3R,4R)-3-Ch lor o-(5E)-1,5-octa d ien -4-ol (16e). IR
(film) ν 3396, 1670, 1640, 1101, 968, 927 cm-1
.
1H NMR
(CDCl3) δ 5.95-5.80 (m, 2H), 5.49-5.43 (m, 1H), 5.35 (ddd, J
) 16.9, 1, 1 Hz, 1H), 5.24 (ddd, J ) 10.2, 1, 1 Hz, 1H), 4.33
(ddd, J ) 14.4, 1, 1 Hz, 1H), 4.16 (t, J ) 6.4 Hz, 1H), 2.06 (m,
2H), 1.88 (m, 1H), 0.99 (t, J ) 3.4 Hz, 3H). 13C NMR (CDCl3)
δ 136.80, 134.95, 126.78, 118.96, 75.30, 67.91, 25.18, 13.19.
CIMS m/ z (isobutane, rel intensity) 143 [(M+ - 18) + 1 (100)],
(100). [R]23 +55.0 (c ) 2.0, CHCl3). Anal. Calcd for C7H13
-
D
OCl: C. 56.57; H, 8.82. Found: C, 56.72; H, 8.77.

7518 J . Org. Chem., Vol. 61, No. 21, 1996
Hu et al.
Ta ble 3. Ha loa llylbor a tion of Ald eh yd es w ith Rea gen ts
13a -d a
Ta ble 4. Effect of P r op or tion of BF 3‚OEt2 on th e EE of
Ch lor oh yd r in sa
syn-
halohydrin,
cis-
BF3‚OEt2
(equiv)
R′ in
R′CHO
syn-R-chlorohydrin
16, ee %b
vinyloxiraneb
entry R in LiNR2
yield, ee, yield,
ee,
cis/
1
2
3
4
5
6
7
8
9
c-Hex
i-Pr
c-Hex
i-Pr
i-Pr
c-Hex
i-Pr
c-Hex
i-Pr
i-Pr
2.5
2.5
2.5
2.5
1.33
2.5
1.33
2.5
2.5
1.33
c-Hex
c-Hex
Ph
Ph
Ph
t-Bu
t-Bu
n-C8H17
n-C8H17
n-C8H17
95
93.5
98
84
95
78
77
94
93
92
c
d
c
d
entry
R′CHO R′ )
1
2
%
%
%
%
transe
1
2
3
n-C8H17
i-Pr
Ph
1a 2b
1a 2b
1a 2b
1a 2b
1a 2b
1a 2b
70
68
78
77
72
85
78
75
65
77
71
75
78
70
68
98
95
98
76
95
90
99
93h
78
95
94
97
96
94
93
95
99
96
97
94
98
95
85i
90
98
97
98
96
97
92
98f
95f
97
75
93
90
97
92f
77
93
92
94
94
94
92
99:1
98:2
98:2
99:1
98:2
99:1
99:1
98:2
97:3
96:4
94:6
98:2
98:2
95:5
94:6
4g Ph
5
6
7
8
9
10
11
12
13
14
15
c-Hex
PhCH2
(E)-EtCHdCH 1a 2b
(E)-PhCHdCH 1a 2b
t-Bu
Ph
c-Hex
Ph
c-Hex
c-Hex
Ph
10
1a 2b
1b 2b
1b 2b
1a 2c
1a 2c
1b 2c
1b 2c
a
Ate complex formation, decomposition and aldehyde addition
at -95 °C. dIpc2BOMe was used. ee’s determined by GC (Cy-
b
clodex B, 30 m × 0.25 mm i.d. column using conditions given in
Table 3).
Ta ble 5. Effect of Lith iu m Dia lk yla m id e Ba se Str u ctu r e
on Ster eoselectivity of Ch lor oh yd r in F or m a tion a
a
Li(c-Hex)2. Ate complex formation, decomposition (2.5 equiv
of BF3‚OEt2) and aldehyde addition at -95 °C (for solvent details
R-chlorohydrin, 16
b
see Experimental Section). Obtained by cyclization of chlorohy-
lithium
dialkylamide used
R′CHO
R′ )
dsc
syn vs anti
drins with K2CO3/MeOH, unless noted. If oxiranes are insensitive
to base (except entries 3, 6 and 7), they can be obtained by
oxidation of intermediates 14 or 15 (NaOH/H2O2), without isolation
entry
ee (%)b
1
2
3
4
5
6
LDA
LDA
LiTMP
Li(i-Pr)c-Hex
LiN(c-Hex)2
LiN(c-Hex)2
c-Hex
Ph
c-Hex
c-Hex
c-Hex
Ph
94
82
94
93
96
98
97:3
95:5
>99:1
97:3
>99:1
99:1
d
of chlorohydrin. c Isolated yields. Ee’s determined by GC (Cyclo-
dex B, 30 m × 0.25 mm i.d. column, carrier gas He at 15 psi,
temperature between 100 °C and 200 °C, isothermal), unless noted.
The racemic compounds prepared using 9-methoxy-9-BBN instead
of Ipc2BOMe. e Determined by 1H NMR and capillary GC analysis.
These ratios were same as syn/ anti ratios of chlorohydrins
(determined by capillary GC analyses). f ee determined by 1H NMR
Reactions at -95 °C using dIpc2BOMe and 2.5 equiv of
a
b
BF3‚OEt2. ee’s determined by GC (Cyclodex B, 30 m × 0.25 mm
g
analysis (400 MHz) using Eu(hfc)3. Reaction conducted in THF.
ID column, using conditions in Table 3). c de’s determined by 1H
NMR and capillary GC analysis.
h
i
Determined by 1H NMR analysis of MTPA ester. Cyclized using
KO-t-Bu/THF.
163 [M+ + 1 (13.1)], 145 (83.8), 127 (100), 109 (62.1). [R]23
Sch em e 6
D
+38.60 (c ) 3.50, CHCl3). Anal. Calcd for C8H15ClO: C, 59.07;
H, 9.30. Found: C, 59.29; H, 9.20.
syn -(1R,2R)-2-Br om o-1-cycloh exyl-3-bu ten -1-ol (16i). IR
(film) ν 3378, 1494, 1278, 1087 cm-1 1H NMR (CDCl3) δ 6.11
.
(ddd, J ) 16.9, 10, 10 Hz, 1H), 5.31 (ddd, J ) 16.9, 1, 1 Hz,
1H), 5.15 (ddd, J ) 10, 1, 1 Hz, 1H), 4.70 (dd, J ) 17.6, 5.4
Hz, 1H), 3.26 (dd, J ) 12, 5.6 Hz, 1H), 1.96 (d, J ) 6.6 Hz,
1H), 1.84-1.14 (m, 11H). 13C NMR (CDCl3) δ 136.49, 118.04,
78.09, 62.26, 41.56, 29.79, 26.84, 26.49, 26.22, 25.91. CIMS
m/ z (isobutane rel intensity) 217 [(M+ + 2) - 18 + 1 (13.4)],
215 [(M+ - 18) + 1, (13.4)], 153 (81.4), 135 (63.5), 111 (100).
[R]23 +25.52 (c ) 3.02, Et2O). Anal. Calcd for C10H17BrO:
Sch em e 7
D
C, 51.71; H, 7.38. Found: C, 51.90; H, 7.35.
syn -(1R,2R)-2-Br om o-1-p h en yl-3-bu ten -1-ol (16j). IR
(film) ν 3445, 1640, 1489, 1425, 1048, 989, 926 cm-1 1H NMR
.
(CDCl3) δ 7.18-7.43 (m, 5H), 5.94 (ddd, J ) 17.6, 10.2, 8 Hz,
1H), 5.13 (ddd, J ) 17.6, 1, 1 Hz, 1H), 5.03 (ddd, J ) 10, 1, 1
Hz, 1H), 4.74 (dd, J ) 7.2, 4.1 Hz, 1H), 4.43 (dd, J ) 4.1, 3.6
Hz, 1H), 2.81 (d, J ) 3.6 Hz, 1H). 13C NMR (CDCl3) δ 135.27,
129.79, 129.04, 128.62, 126.55, 119.19, 77.04, 63.35. CIMS
m/ z (isobutane, rel intensity) 211 [(M+ + 2) - 18 (44.3)], 209
[(M+ - 18 (44.3)], 147 (35.9), 129 (59.7), 107 (100). [R]23
D
+36.78 (c ) 2.31, CHCl3). Anal. Calcd for C10H11OBr: C,
53.10; H, 4.91. Found: C, 53.08; H, 4.98.
syn -(1S,2S)-2-Br om o-1-cycloh exyl-3-b u t en -1-ol (17a ).
[R]23 -25.27 (c ) 2.91, Et2O).
D
syn -(1S,2S)-2-Br om o-1-p h en yl-3-bu ten -1-ol (17b). [R]23
D
-34.68 (c ) 2.13, CHCl3).
syn -(1S,2S)-2-Ch lor o-1-cycloh exyl-3-b u t en -1-ol (17c).
[R]23 -52.57 (c ) 2.21, CHCl3).
D
syn -(1S,2S)-2-Ch lor o-1-p h en yl-3-bu ten -1-ol (17d ). [R]23
D
-18.50 (c ) 2.0, CHCl3).
syn -(3R,4R)-4-Ch lor o-2,2-d im eth yl-5-h exen -3-ol (16h ).
IR (film) ν 3396, 1670, 1640, 1101, 968, 927 cm-1 1H NMR
(CDCl3) δ 6.05 (ddd, J ) 16.9, 10.2, 1 Hz, 1H), 5.31 (ddd, J )
16.9, 1, 1 Hz, 1H), 5.17 (ddd, J ) 10.2, 1, 1 Hz, 1H), 4.64 (dd,
J ) 4.8, 3.6 Hz, 1H), 3.36 (dd, J ) 7.8, 3.6 Hz, 1H), 2.24 (d, J
) 7.8 Hz, 1H), 1.00 (s, 9H). 13C NMR (CDCl3) δ 137.61, 117.06,
80.34, 66.32, 35.73, 26.77. CIMS m/ z (isobutane, rel intensity)
.
Syn th esis of cis-Vin ylep oxid es 18/19. (i) Gen er a l P r o-
ced u r e for Oxid a tion of Bor on In ter m ed ia tes 14/15. The
residue obtained (see experimental procedure for preparation
of 16a ) was dissolved in THF (20 mL) with stirring and cooled
to 0 °C. Then, 3 M NaOH (12 mL) and 30% H2O2 (12 mL)
were sequentially added. The reaction mixture was allowed

Synthesis of syn-R-Vinylchlorohydrins and cis-Vinylepoxides
J . Org. Chem., Vol. 61, No. 21, 1996 7519
to warm to rt (14 h). Standard workup followed by flash
chromatography yielded a colorless liquid, 18a (1.29 g, 74%
yield).
cis-(3R,4S)-3,4-Epoxy-5-m eth yl-1-h exen e (18g). IR (film)
ν 3034, 1641, 1244, 1197 cm-1
.
1H NMR (CDCl3) δ 5.75 (ddd,
J ) 17.2, 10.4, 7.4, 1H), 5.47 (ddd, J ) 17.2, 1, 1 Hz, 1H), 5.33
(ddd, J ) 10.4, 1, 1 Hz, 1H), 3.44 (dd, J ) 7.4, 4.4 Hz, 1H),
2.74 (dd, J ) 7.4, 4.4 Hz, 1H), 1.49-1.40 (m, 1H), 1.07 (d, J )
1.3 Hz, 3H), 0.91 (d, J ) 1.3 Hz, 3H). 13C NMR (CDCl3) δ
133.78, 120.69, 65.65, 58.78, 28.13, 20.27, 18.38. EIMS m/ z
112 [M+ (11.2)], 97 (26.5), 83 (18.7), 79 (13.4), 69 (68.7), 56
(100), 41 (29.7). [R]23D -69.60 (c ) 1.25, EtOH). HRMS Calcd
for C7H12O: 112.0888. Found: 112.0885.
(ii) Gen er a l P r oced u r e for Cycliza tion of syn -r-Ch lo-
r oh yd r in s. To a solution of R-chlorohydrin 16d (0.95 g, 5
mmol) in MeOH (40 mL) was added K2CO3 (1.20 g, 10.0 mmol).
This mixture was stirred for 6 h after which time most MeOH
was removed in vacuo. The resulting slurry was then diluted
with water (20 mL), and the mixture was extracted with Et2O
(3 × 40 mL). Standard workup followed by flash chromatog-
raphy (hexane:Et2O, 99:1) gave cis-vinyloxirane 18d (0.74 g,
98% yield).
cis-(3R,4S)-3,4-Ep oxy-2,2-d im eth yl-5-h exen e (18h ). 1H
NMR (CDCl3) δ 5.94 (ddd, J ) 17.8, 10.4, 8 Hz, 1H), 5.47 (dd,
J ) 17.8, 1 Hz, 1H), 5.27 (dd, J ) 10.2, 1 Hz, 1H), 3.47 (dd, J
) 8.0, 4.5 Hz, 1H), 2.82 (d, J ) 4.5 Hz, 1H), 1.00 (s, 9H). 13C
NMR (CDCl3) δ 134.08, 119.44, 67.19, 59.07, 33.63, 27.60.
CIMS m/ z (isobutane, rel intensity) 143 [(M+ - 18) + 1 (100)],
cis-(1R,2S)-1-Cycloh exyl-1,2-ep oxy-3-bu ten e (18a ). IR
(film) ν 1449, 1256, 1182, 985, 922, 823, 789 cm-1 1H NMR
.
(CDCl3) δ 5.72 (ddd, J ) 17.2, 10, 7.4, 1H), 5.47 (ddd, J ) 17.2,
1, 1 Hz, 1H), 5.33 (ddd, J ) 10, 1, 1 Hz, 1H), 3.39 (dd, J ) 7.5,
4.4 Hz, 1H), 2.77 (q, J ) 4.4 Hz, 1H), 1.77-1.13 (m, 11H). 13C
NMR (CDCl3) δ 133.57, 120.15, 63.45, 57.78, 36.13, 31.67,
28.95, 26.24, 25.78, 25.09. CIMS m/ z (isobutane, rel intensity)
125 (29.8), 107 (57.5). [R]23 +15.89 (c ) 1.45, EtOH). Anal.
D
Calcd for C8H14O: C, 76.13; H, 11.19. Found: C, 76.04; H,
11.24.
cis-(1S,2R)-1-Cycloh exyl-1,2-epoxy-3-bu ten e (19a). [R]23
153 [M+ + 1 (100)], 135 (68.5), 125 (8.7). [R]23 +35.18 (c )
D
D
-38.58 (c ) 2.68, EtOH).
2.08, EtOH). Anal. Calcd for C10H16O: C, 78.89; H, 10.59.
Found: C, 79.15; H, 10.73.
cis-(1S,2R)-1,2-Ep oxy-1-p h en yl-3-bu ten e (19b). [R]23
D
-90.16 (c ) 2.05, EtOH).
cis-(1R,2S)-1,2-Epoxy-1-ph en yl-3-bu ten e (18b). IR (film)
ν 1496, 1442, 1388, 1250, 1181, 986, 927, 821, 787 cm-1 1H
.
Gen er a l P r oced u r e for Ch lor oa llylbor a tion of Ald e-
h yd es Usin g 9-MeO-9-BBN. To a stirred and cooled (-78
°C) mixture of MeO-9-BBN (11.5 mmol) and allyl chloride (15
mmol) in anhyd ether (50 mL) was added a solution of LiN-
(c-Hex)2 (15 mmol) in THF (25 mL). After stirring for 0.5 h,
BF3‚OEt2 (30 mmol) was added followed by cyclohexanecar-
boxaldehyde (11.5 mmol). The reaction mixture was stirred
for 3 h at -78 °C, then the cold bath was removed and the
flask allowed to warm to rt. All solvents were removed in
vacuo, and the residue was triturated with n-pentane (40 mL)
and allowed to settle (12 h). The supernatant was transferred
to another predried flask through a cannula. The residue was
further treated with pentane (2 × 30 mL), and the pentane
extracts were combined. Removal of pentane in vacuo fur-
nished a semisolid. This was dissolved in ether and treated
with ethanolamine following the reported procedure.19 Stan-
dard workup followed by flash chromatography (hexane:ether,
95:5) yielded a mixture of 6a , 7a , and 8a .
NMR (CDCl3) δ 7.36-7.25 (m, 5H), 5.57-5.53 (m, 1H), 5.43-
5.34 (m, 1H), 5.29-5.26 (m, 1H), 4.25 (d, J ) 4.1 Hz, 1H), 3.67
(q, J ) 4.1 Hz, 1H). 13C NMR (CDCl3) δ 135.19, 132.15, 128.54,
128.13, 127.73, 126.48, 125.53, 121.84, 59.78, 58.85. CIMS
m/ z (rel intensity) 147 [M+ + 1 (100)], 146 [M+ (12.5)], 129
(54.7), 119 (11.7), 117 (14.4), 105 (23.0). [R]23 +97.36 (c )
D
2.65, EtOH). Anal. Calcd for C10H10O: C, 82.16; H, 6.89.
Found: C, 82.23; H, 6.99.
cis-(3R,4R)-3,4-Epoxy-1-dodecen e (18c). IR (film) ν 1639,
1465, 1256, 984, 922, 815 cm-1 1H NMR (CDCl3) δ 5.71 (ddd,
.
J ) 17.2, 10.4, 7.2 Hz, 1H), 5.46 (ddd, J ) 17.2, 1, 1 Hz, 1H),
5.34 (ddd, J ) 10.2, 1, 1 Hz, 1H), 3.39 (dd, J ) 7.2, 4.3 Hz,
1H), 3.06 (m, 1H), 1.58-0.85 (m, 17H). 13C NMR (CDCl3) δ
132.79, 120.04, 58.74, 57.12, 31.80, 29.39, 29.15, 27.73, 26.26,
22.60, 13.98. CIMS m/ z (isobutane, rel intensity) 183 [M+
+
1 (27)], 165 [(M+ - 18) + 1 (12.5)], 141 (100). [R]23 +15.7 (c
D
) 1.56, EtOH). Anal. Calcd for C12H22O: C, 79.06; H, 12.16.
Found: C, 79.01; H, 12.20.
Preparation of (() cis-vinylepoxide 9b by oxidation of boron
intermediate employed a procedure analogous to that described
for the synthesis of 18a .
cis-(2R,3S)-2,3-Epoxy-1-ph en yl-4-pen ten e (18d). IR (film)
ν 3086, 1639, 1496, 1250, 985, 928, 871, 778 cm-1 1H NMR
.
(Z)-4-Ch lor o-1-p h en yl-3-bu ten -1-ol (6a ). 1H NMR and
13C NMR spectra of 6a are in agreement with those reported.29
CIMS m/ z (isobutane, rel intensity) 165 [(M+ - 18) + 1 (100)],
147 (29.8), 129 (100).
(CDCl3) δ 7.35-7.23 (m, 5H), 5.90 (ddd, J ) 17.2, 10.4, 6.9
Hz, 1H), 5.57 (ddd, J ) 17.2, 1, 1 Hz, 1H), 5.46 (ddd, J ) 10.4,
1, 1 Hz, 1H), 3.52 (dd, J ) 6.9, 4.2 Hz, 1H), 3.33 (ddd, J ) 6.1,
6.1, 4.2 Hz, 1H), 2.96 (dd, J ) 14.8, 6.0 Hz, 1H), 2.82 (dd, J )
14.8, 6.7 Hz, 1H). 13C NMR (CDCl3) δ 137.68, 132.47, 128.90,
128.64, 126.64, 120.56, 58.96, 57.24, 34.17. EIMS m/ z (rel
intensity) 160 [M+ (9.7)], 142 (43.3), 131 (17.5), 117 (14.3), 104
(87.5), 103 (47.3), 91 (100), 78 (53.2), 69 (52.8), 51 (18.9), 41
(Z)-4-Ch lor o-1-cycloh exyl-3-b u t en -1-ol (6b). 1H NMR
(CDCl3) δ 6.13 (dd, J ) 7.1, 1.0 Hz, 1H), 5.90 (dd, J ) 9.4, 7.1
Hz, 1H), 3.44-3.49 (m, 1H), 2.60 (s, 1H), 2.32-2.49 (m, 2H),
1.88-1.66 (m, 6H), 1.02-1.39 (m, 5H). 13C NMR (CDCl3) δ
128.6, 119.8, 75.2, 43.5, 32.2, 29.2, 28.0, 26.5, 26.3. CIMS m/ z
(isobutane, rel intensity) 173 [(M+ - 18) + 2 + 1 (8.4)], 171
[(M+ - 8) + 1 (28)], 135 (100). Anal. Calcd for C10H17ClO: C,
63.65; H, 9.08. Found: C, 63.50; H, 9.12.
(11.2). [R]23 +15.48 (c ) 3.08, EtOH). Anal. Calcd for
D
C11H12O: C, 82.46; H, 7.55. Found: C, 82.30; H, 7.56.
cis-(3R,4S)-3,4-Ep oxy-(5E)-1,5-octa d ien e (18e). IR (film)
ν 3088, 1641, 1244, 984, 927, 840, 792 cm-1 1H NMR (CDCl3)
.
(Z)-4-Br om o-1-p h en yl-3-bu ten -1-ol (6c). 1H NMR and
13C NMR spectra of 6c are in agreement with those reported.29
CIMS m/ z (isobutane, rel intensity) 211 [(M+ + 2 ) - 18 (13.4)],
209 [(M+ - 18) (13.4)], 153 (21.4), 135 (100).
δ 6.01 (dt, J ) 15.5, 6.4 Hz, 1H), 5.78 (ddd, J ) 17.3, 10.2, 7.1
Hz, 1H), 5.50 (dd, J ) 17.3, 1.5 Hz, 1H), 5.37 (dd, J ) 10.2,
1.5 Hz, 1H), 5.26-5.33 (m, 1H), 3.54 (m, 2H), 2.10 (m, 2H),
1.00 (t, J ) 7.6 Hz, 3H). 13C NMR (CDCl3) δ 139.99, 132.71,
122.80, 120.37, 58.84, 58.80, 25.58, 13.18. CIMS m/ z (isobu-
tane, rel intensity) 183 [M+ + 1 (21.3)], 165 (12.1), 141 (100),
(Z)-4-Br om o-1-cycloh exyl-3-bu ten -1-ol (6d ). 1H NMR
(CDCl3) δ 6.27 (m, 2H), 3.48 (ddd, J ) 12.0, 5.6, 4 Hz, 1H),
2.41 (dd, J ) 4.8, 4 Hz, 1H), 2.34 (m, 1H), 2.15 (s, 1H), 1.87-
0.99 (m, 11H). 13C NMR (CDCl3) δ 131.9, 109.5, 75.1, 43.5,
34.8, 29.2, 28.0, 26.5, 26.3, 26.1. CIMS m/ z (isobutane, rel
intensity) 217 [(M+ + 2 ) - 18 + 1 (7.4)], 215 [(M+ - 18) + 1
(6.9)], 135 (78), 111 (100). Anal. Calcd for C10H17BrO: C,
51.52; H, 7.35. Found: C, 51.65; H, 7.50.
123 (3.7). [R]23 + 30.83 (c ) 1.05, EtOH). Anal. Calcd for
D
C8H12O: C, 77.38; H, 9.74. Found: C, 77.20; H, 9.90.
cis-(3R,4S)-3,4-Epoxy-1-ph en yl-(1E)-1,5-h exadien e (18f).
IR (film) ν 1641, 1494, 1451, 984, 927 cm-1 1H NMR (CDCl3)
.
δ 7.42-7.23 (m, 5H), 6.78 (d, J ) 16 Hz, 1H), 6.25 (dd, J ) 16,
7.6 Hz, 1H), 5.81 (ddd, J ) 17.2, 10.2, 7.2 Hz, 1H), 5.63 (ddd,
J ) 17.2, 1, 1 Hz, 1H), 5.41 (ddd, J ) 10.2, 1, 1 Hz, 1H), 3.74
(ddd, J ) 7.6, 4, 1 Hz, 1H), 3.65 (dd, J ) 7.2, 4 Hz, 1H). 13C
NMR (CDCl3) δ 136.35, 135.70, 132.51, 128.67, 128.33, 128.15,
126.57, 123.49, 120.70, 59.29, 58.85. EIMS m/ z (rel intensity)
172 [M+ (9.7)], 144 (10.1), 143 (33.9), 129 (17.7), 128 (37), 117
a n ti-2-Ch lor o-1-p h en yl-3-bu ten -1-ol (8a ). 1H NMR and
13C NMR spectra of 8a are in agreement with those reported.17b
a n ti-2-Ch lor o-1-cycloh exyl-3-bu ten -1-ol (8b). 1H NMR
and 13C NMR spectra of 8b are in agreement with those
reported.17b
(17.7), 116 (23.5), 115 (100), 65 (10.5), 63 (11.1), 50 (12.7). [R]23
D
+102.0 (c ) 0.7, EtOH). HRMS Calcd for C12H12O : 172.0888.
(29) (a) Hoffmann, R. W.; Landmann, B. Chem. Ber. 1986, 119, 1039.
(b) Hoffmann, R. W.; Landmann, B. Chem. Ber. 1986, 119, 2013.
Found: 172.0882.

7520 J . Org. Chem., Vol. 61, No. 21, 1996
Hu et al.
a n ti-2-Br om o-1-p h en yl-3-b u t en -1-ol (8c). 1H NMR
(CDCl3) δ 7.28-7.36 (m, 5H), 6.06 (dt, J ) 17.0, 10.2 Hz, 1H),
5.17 (d, J ) 17.6 Hz, 1H), 5.13 (d, J ) 10.2 Hz, 1H), 4.98 (d,
J ) 4.4 Hz, 1H), 4.73 (q, J ) 4.4 Hz, 1H), 2.79 (s, 1H); 13C
NMR (CDCl3) δ 139.53, 134.09, 128.74, 128.45, 126.89, 119.80,
EIMS m/ z (rel intensity) 147 [M+ + 1 (100)], 146 [M+ (12.5)],
129 (61.7), 119 (15.7), 117 (12.3), 105 (28.5).
tr a n s-1-Cycloh exyl-1,2-ep oxy-3-bu ten e (9d ). 1H NMR
and 13C NMR spectra of 9d are in agreement with those
reported.17b CIMS m/ z (isobutane, rel intensity) 153 [(M+
1) (100)], 135 (78.5), 125 (15.7).
+
77.21, 60.45. CIMS m/ z (isobutane, rel intensity) 211 [(M+
+
2) - 18 (42.3)], 209 [(M+ - 18) (44.6)], 147 (35.9), 129 (59.7),
107 (100). Anal. Calcd for C10H11BrO: C, 52.89; H, 4.88.
Found: C, 53.01; H, 4.95.
Ack n ow led gm en t. We thank the National Sciences
and Engineering Research Council, Canada, for finan-
cial support through a research grant to ACO.
a n ti-2-Br om o-1-cycloh exyl-3-bu ten -1-ol (8d ). 1H NMR
(CDCl3) δ 6.12 (ddd, J ) 17.0, 10.8, 10 Hz, 1H), 5.30 (ddd, J )
17.0, 1, 1 Hz, 1H), 5.19 (ddd, J ) 10.8, 1, 1 Hz, 1H), 4.74 (dd,
J ) 10, 3.6 Hz, 1H), 3.55 (dd, J ) 8, 3.6 Hz, 1H), 2.20 (s, 1H),
2.00 (m, 1H), 1.74-0.97 (m, 10H). 13C NMR (CDCl3) δ 134.57,
119.08, 78.50, 59.73, 40.47, 29.05, 28.72, 26.30, 25.96, 25.80.
CIMS m/ z (isobutane, rel intensity) 217 [(M+ + 2) - 18 + 1
(13.4)], 215 [(M+ - 18) + 1 (12.6)], 153 (39.4), 135 (100). Anal.
Calcd for C10H17BrO: C, 51.52; H, 7.35. Found: C, 51.60; H,
7.45.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 18f and 18g (4 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered
from the ACS; see any current masthead page for ordering
information.
tr a n s-1,2-Ep oxy-1-p h en yl-3-bu ten e (9c). 1H NMR and
13C NMR spectra of 9c are in agreement with those reported.17b
J O960875P