Asymmetric Synthesis of Serricornin via Boronic Esters

Article abstract of DOI:10.1021/jo980432g

Highly stereoselective boronic ester chemistry has been used for the synthesis of (4S,6S,7S)-7- hydroxy-4,6-dimethylnonanone (1), the pheromone of the cigarette beetle. 2-Bromo-1-butene (8) was made from 1-butyne via bromoboration and protodeboronation, and was converted to 1-ethylethenylmagnesium bromide. (R,R)-1,2-Dicyclohexyl-1,2-ethanediol ["(R)-DICHED"] methylboronate was treated with (dichloromethyl)lithium to yield (R)-DICHED (S)-1-chloroethylboronate (9), which with 1-ethylethenylmagnesium bromide yielded (R)-DICHED (R)-(2-ethyl-1-methyl-2- propenyl)boronate (10). Further chain extensions with (chloromethyl)lithium, (dichloromethyl)- lithium followed by methylmagnesium bromide, and (dichloromethyl)lithium followed by ethyl- magnesium bromide completed assembly of the carbon skeleton. Deboronation with hydrogen peroxide yielded (3S,5S,6S)-2-ethyl-3,5-dimethylocten-6-ol (14), which with osmium tetraoxide and sodium periodate yielded 1.

Full text of DOI:10.1021/jo980432g

4
466
J . Org. Chem. 1998, 63, 4466-4469
Asym m etr ic Syn th esis of Ser r icor n in via Bor on ic Ester s
Donald S. Matteson,* Rajendra Prasad Singh, Bonnie Schafman, and J ing-jing Yang
Department of Chemistry, Washington State University, Pullman, Washington 99164-4630
Received March 9, 1998
Highly stereoselective boronic ester chemistry has been used for the synthesis of (4S,6S,7S)-7-
hydroxy-4,6-dimethylnonanone (1), the pheromone of the cigarette beetle. 2-Bromo-1-butene (8)
was made from 1-butyne via bromoboration and protodeboronation, and was converted to
1
-ethylethenylmagnesium bromide. (R,R)-1,2-Dicyclohexyl-1,2-ethanediol [“(R)-DICHED”] meth-
ylboronate was treated with (dichloromethyl)lithium to yield (R)-DICHED (S)-1-chloroethylboronate
9), which with 1-ethylethenylmagnesium bromide yielded (R)-DICHED (R)-(2-ethyl-1-methyl-2-
(
propenyl)boronate (10). Further chain extensions with (chloromethyl)lithium, (dichloromethyl)-
lithium followed by methylmagnesium bromide, and (dichloromethyl)lithium followed by ethyl-
magnesium bromide completed assembly of the carbon skeleton. Deboronation with hydrogen
peroxide yielded (3S,5S,6S)-2-ethyl-3,5-dimethylocten-6-ol (14), which with osmium tetraoxide and
sodium periodate yielded 1.
In tr od u ction
The pheromone of the cigarette beetle, Lasioderma
We have shown that it is possible to cleave the chiral
director (R)-(R*,R*)-1,2-dicyclohexylethane-1,2-diol [(R)-
DICHED] from boron and replace it by its (S)-enanti-
serricorne F. (Anobiidae), a pest of dried foodstuffs and
7
omer, but the most efficient synthetic strategy requires
tobacco, is (4S,6S,7S)-7-hydroxy-4,6-dimethylnonanone
use of a single chiral director throughout the synthesis
if possible. This requirement rules out the route via (S)-
DICHED boronic ester 4, the enantiomer of an interme-
1
(
1), which exists as an equilibrium mixture with its cyclic
hemiacetal tautomer 2. The attractant activity is inhib-
ited by the (4S,6S,7R)-isomer (3) at the 10% level, but
the (4S,6R,7R)-isomer and the (4S,6R,7S)-isomer have
no apparent effect up to a 1:1 ratio, and it appears that
the four enantiomers of these are also inert. Previous
stereocontrolled syntheses of 1 have been reported from
4
diate used for the stegobinone synthesis, to (R)-DICHED
boronic ester 5, which has to have the opposite chiral
director in order to install the second methyl group
correctly. What is needed instead is a way to construct
the synthetic equivalent of 4 with (R)-DICHED as chiral
director. The benzyloxy group of 4 and 5 would be a
ketone precursor, and stereocontrol at this site is ir-
relevant.
2
microbially produced methyl (R)-3-hydroxypentanoate
and via asymmetric enolate chemistry.3
Resu lts
A carbon-carbon double bond was chosen as the
masked carbonyl group to carry through the synthesis
of 1. The strategy to achieve the desired chirality
involved reaction of a suitable 1-ethyl-1-metalloalkene
with (R)-DICHED (S)-(1-chloroethyl)boronate (9). An
obvious way to avoid regioisomer problems would be to
use a 3-metallo-3-hexene as the intermediate, but unex-
pected complications were encountered in the hydrobo-
ration of 3-hexyne (see Discussion).
Although the purity requirements for biologically active
serricornin are not nearly as stringent as for stegobinone,
an anobiid beetle pheromone we have synthesized previ-
4
ously, the three stereocenters offer a worthy synthetic
challenge well suited to our asymmetric boronic ester
chemistry.5 Diastereoselections in the 1000:1 range can
be achieved by the use of a chiral director that has C
symmetry, a level of precise stereocontrol well beyond
the minimal requirements for the present synthesis.
2
6
The use of a (2-halo-1-butenyl)magnesium halide was
then undertaken. The classical synthesis of 2-chloro-1-
8
butene from 2-butanone yielded a gross mixture and was
*
To whom correspondence should be addressed.
abandoned in favor of a haloboration strategy. Boron
(1) (a) Kuwahara, Y.; Fukami, H.; Howard, R.; Ishii, S.; Matsumura,
F.; Burkholder, W. E. Tetrahedron 1978, 34, 1769-1774. (b) Mori, M.;
Mochizuki, K.; Kohno, M.; Chuman, T.; Ohnishi, A.; Watanabe, H.;
Mori, K. J . Chem. Ecol. 1985, 12, 83-89.
(5) (a) Matteson, D. S.; Sadhu, K. M.; Peterson, M. L. J . Am. Chem.
Soc. 1986, 108, 812-819. (b) Matteson, D. S.; Sadhu, K. M. U.S. Patent
4,525,309, J une 25, 1985. (c) Matteson, D. S. Chem. Rev. 1989, 89,
1535-1551. (d) Matteson, D. S.; Soundararajan, R.; Ho, O. C.;
Gatzweiler, W. Organometallics 1996, 15, 152-163.
(6) Tripathy, P. B.; Matteson, D. S. Synthesis 1990, 200-206.
(7) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1996, 61, 6047-6051.
(8) Charpentier, P. Bull. Soc. Chim. Fr. 1934, 1, 1407-1411.
(
2) Mori, K.; Watanabe, H. Tetrahedron 1985, 41, 3423-3428.
3) Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1987, 28, 651-
(
6
54.
(
4) (a) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1993, 58, 6545-
6
1
547. (b) Matteson, D. S.; Man, H.-W.; Ho, O. C. J . Am. Chem. Soc.
996, 118, 4560-4566.
S0022-3263(98)00432-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/05/1998

Synthesis of Serricornin via Boronic Esters
J . Org. Chem., Vol. 63, No. 13, 1998 4467
tribromide and 1-butyne react exothermically to produce
the yields in each step. Although the efficiency of
recovery of the chiral director, (R)-DICHED, was not
measured, it has been shown in previous work that 90%
of a similar chiral director can be recovered if the
byproduct fractions are kept and included in the recy-
cling.10 Thus, the synthesis is highly efficient in its use
of chiral director.
(2-bromobutenyl)boron dibromide (6), which reacts more
slowly with the stoichiometric amount of 1-butyne to form
tris(2-bromobutenylborane) (7). Either 6 or 7 with acetic
acid yielded 2-bromo-1-butene (8).
The overall yield of serricornin based on the achiral
precursors 1-butyne and boron tribromide was not mea-
sured accurately. The yield of purified 2-bromo-1-butene
via the tris(alkenylborane) was 80%, and if it is assumed
that the yield of Grignard reagent was 70-80%, the yield
of serricornin was 33-39%.
The boronic ester chemistry followed established pro-
(R,R)-1,2-Dicyclohexyl-1,2-ethanediol [(R)-
DICHED] (S)-(1-chloroethyl)boronate (9) was prepared
cedures.5
,6
Unsaturated alcohol 14 was the only intermediate in
the sequence that was purified by chromatography.
Despite the lack of rigorous purification of any of the
preceding intermediates in this multistep sequence, the
stereoselectivity and yield in each chain-extension step
were so high that purified 14 was obtained from its crude
predecessor 13 in 89% yield.
from (dichloromethyl)lithium and (R)-DICHED methyl-
boronate as previously described.9 Treatment of 9 with
(1-ethylethenyl)magnesium bromide (from 8 and mag-
nesium in THF) yielded (R)-(2-ethyl-1-methyl-2-prope-
nyl)boronate 10, which was converted by (chloromethyl)-
lithium to (3-ethyl-2-methyl-3-butenyl)boronate 11.
The unusually high stereoselection in the rearrange-
6
ment of (chloroalkyl)borate complexes is a major factor
in making this synthesis practical without purification
of intermediates at every step. A rational basis for the
stereoselectivity has recently been postulated by Corey,
Barnes-Seeman, and Lee,11 and quantum-mechanical
calculations by Midland have independently led to a
similar conclusion.12
The procedures reported here utilized preformed (dichlo-
romethyl)lithium for laboratory convenience, which re-
quires cooling to -100 °C. However, it should be noted
that a practical temperature for scale-up, -40 °C, has
been used successfully with a number of similar prepara-
tions merely by generating the (dichloromethyl)lithium
from dichloromethane and lithium diisopropylamide in
the presence of the boronic ester.4
,5,13
At the outset of this work, it was expected that
hydroboration of 3-hexyne with catecholborane would
produce a single regio- and stereoisomer,14 which could
be converted to a single geometric isomer of 3-bromo-3-
hexene,15 then to 3-lithio-3-hexene, for reaction with (R)-
DICHED (S)-(1-chloroethyl)boronate (9) to form the
propylidene analogue of (R-methylenealkyl)boronic ester
1
0. However, commercial catecholborane with 3-hexyne
yielded gross (E,Z)-mixtures as a result of free radical
side reactions, and (Z)-3-hexenyl-3-boronic esters isomer-
ize thermally to (E,Z)-mixtures, reported in detail else-
where.16 Such mixtures would have unduly complicated
the characterization of a series of intermediates, hence,
the use of 2-bromo-1-butene (8) instead.
Chain extension with (dichloromethyl)lithium and
methylation with methylmagnesium bromide yielded
intermediate 12, and a final chain extension with (dichlo-
romethyl)lithium and ethylation with ethylmagnesium
bromide completed the carbon skeleton, boronic ester 13.
Deboronation of 13 yielded key intermediate alkenol 14,
which was cleaved to serricornin (1) by sodium periodate
with a catalytic amount of osmium tetraoxide. Purifica-
tion of 14 was easily accomplished by distillation. Ser-
ricornin undergoes dehydration from cyclic tautomer 2
to enol ether 15 if distilled without prior removal of all
traces of acid.
The best alternative synthesis utilizes asymmetric
aldol and enolate alkylation processes.3 The chiral
director used for both carbon-carbon bond connections,
(S-trans)-2,5-bis[(methoxymethoxy)methyl]pyrrolidine, re-
(
(
9) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1996, 61, 6047-6051.
10) Matteson, D. S.; Tripathy, P. B.; Sarkar, A.; Sadhu, K. M. J .
Am. Chem. Soc. 1989, 111, 4399-4402.
(
11) Corey, E. J .; Barnes-Seeman, D.; Lee, T. W. Tetrahedron:
Asymmetry 1997, 8, 3711-3713.
(
(
12) Midland, M. M. J . Org. Chem. 1998, 63, 914-915.
13) Matteson, D. S.; Hurst, G. D. Organometallics 1986, 5, 1465-
1
4
1
467.
(
14) Brown, H. C.; Gupta, S. K. J . Am. Chem. Soc. 1972, 94, 4370-
371.
Discu ssion
(15) Matteson, D. S.; Liedtke, J . D. J . Am. Chem. Soc. 1965, 87,
526-1531.
The overall yield of serricornin from (R)-DICHED
(16) Schafman, B.; Matteson, D. S. Main Group Met. Chem. 1996,
methylboronate was 59%, calculated as the product of
19, 705-710.

4
468 J . Org. Chem., Vol. 63, No. 13, 1998
Matteson et al.
3
quired a multistep synthesis involving resolution, as did
150 mmol) in THF (tetrahydrofuran) (200 mL) and butyl-
lithium (47.5 mL of 1.6 M solution in hexane, 76 mmol) at
-100 °C. After 5 min, a solution of [4R-(4R,5â)]-4,5-dicyclo-
hexyl-2-methyl-1,3,2-dioxaborolane (18.0 g, 72 mmol) in THF
the chiral director for an earlier synthesis of the inter-
mediate (S,S)-2-methyl-3-hydroxypentanoic acid.17 More
recent technology could no doubt improve the practicality
of this alternative approach.
(100 mL) was added via cannula to the stirred mixture.
Anhydrous zinc chloride (7.8 g, 58 mmol) was added. The
solution was allowed to warm to 20-25 °C and stirred for 24
h. The solvent was removed under vacuum. Ether was added,
and the mixture was washed with saturated ammonium
chloride solution. The organic phase was dried over anhydrous
magnesium sulfate and filtered. Concentration at reduced
Exp er im en ta l Section
Gen er a l Meth od s. The usual procedures for handling
reactive organometallic reagents were followed, including the
use of an inert atmosphere (argon) and THF (tetrahydrofuran)
that had been rigorously dried over sodium benzophenone
ketyl. Detailed directions for carrying out reactions of boronic
esters with (dichloromethyl)lithium have been reported
previously.
-Br om o-1-Bu t en e (8). A. Via (2-Br om ob u t en yl)-
d ibr om o)bor a n e. 1-Butyne (21.63 g, 31.9 mL, 400 mmol)
pressure yielded [4R-[2(S*),4R,5â]]-4,5-dicyclohexyl-2-(1-chlo-
1
roethyl)-1,3,2-dioxaborolane (7) (21.2 g, 98%); 300 MHz
H
NMR (CDCl ) δ 0.88-1.79 (m,22), 1.55 (d, 3), 3.45 (q, J ) 7.5
3
Hz, 1), 3.82-3.96 (m, 2); 75 MHz 13C NMR (CDCl ) δ 20.6,
3
4
-6
25.7, 25.9, 26.3, 27.1, 28.0, 37.9, 42.7, 84.0; HRMS calcd for
+
2
C
C
16
H
H
28BClO
28BClO
2
(M ) 298.1871, found 298.1864. Anal. Calcd for
: C, 64.35; H, 9.45; B, 3.62; Cl, 11.87. Found: C,
(
16
2
was condensed in a flask at -78 °C under argon, and boron
tribromide (100.2 g, 37.81 mL, 400 mmol) was added dropwise.
An exothermic reaction occurred, with the evolution of white
fumes. After addition of boron tribromide, the neat reaction
mixture was stirred at -78 °C for 0.5 h. Pentane (1 L) was
added slowly at -78 °C. The resulting orange homogeneous
solution was poured slowly onto excess crushed ice. (CAU-
TION: Hydrogen bromide evolution occurs.) The pentane
solution was separated, the aqueous phase was extracted with
pentane, and the combined pentane solution was concentrated
to ∼300 mL and then treated with glacial acetic acid (24 mL).
The mixture was stirred at 20-25 °C for 24 h or under reflux
for 16 h. Excess acetic acid was neutralized with sodium
carbonate solution and washed with water. The solution was
dried over anhydrous magnesium sulfate, filtered, and con-
centrated under reduced pressure. 2-Bromo-1-butene was
distilled under vacuum (1 Torr) from a flask immersed in a
64.63; H, 9.51; B, 3.37; Cl, 11.97.
Br om o(1-eth yleth en yl)m a gn esiu m (1-Bu ten -2-ylm a g-
n esiu m br om id e). This Grignard reagent was prepared in
the usual manner from magnesium turnings (3.2 g, 113 mmol)
in THF (tetrahydrofuran) (250 mL), and a solution of 2-bromo-
1
-butene (8) (13.5 g, 100 mmol) in THF (50 mL) was added
slowly. The concentration of Grignard reagent was determined
by titration with 2-propanol in THF using 1,10-phenanthroline
as an indicator.
[
4R-[2(R*),4r,5â]]-4,5-Dicycloh exyl-2-(2-eth yl-1-m eth yl-
2
-p r op en yl)-1,3,2-d ioxa bor ola n e (10). (1-Buten-2-yl)mag-
nesium bromide (3.25 M in THF, 60 mmol) was added dropwise
in 0.5 h to [4R-[2(S*),4R,5â]]-4,5-dicyclohexyl-2-(1-chloroethyl)-
1
,3,2-dioxaborolane (9) (17.88 g, 60 mmol) in THF (65 mL)
stirred at -78 °C. The bath was allowed to warm to 20-25
C, and the reaction mixture was stirred for 20 h. The usual
workup procedure (see preparation of 9) yielded colorless liquid
°
bath at <10 °C into a receiver cooled with a -78 °C bath (37.85
1
1
2
3
1
0 (18.13 g, 95%): 300 MHz H NMR (CDCl
3
) δ 0.80-1.77 (m,
1
g, 70%): 300 MHz H NMR (CDCl
3
) δ 1.11 (t, 3), 2.44 (q, 2),
) δ 13.0, 34.9,
4 7
H Br (M ) 133.9731, found
2), 1.04 (d, 3), 1.17 (t, 3), 1.90 (q, 1), 2.00 (m, 1), 2.10 (m, 1),
.83 (d, 2), 4.72 +4.73 (AB, 2); 75 MHz C NMR (CDCl
2.3, 14.8, 25.9, 26.4, 27.3, 28.12, 29.3, 43.0, 83.3, 105.5, 154.0;
5
1
1
.33 (s, 1), 5.52 (d, 1); 75 MHz 13C NMR (CDCl
14.9, 136.1; HRMS calcd for C
33.9713.
3
13
3
) δ
+
+
HRMS calcd for C20
4R-[2(S*),4r,5â]]-4,5-Dicycloh exyl-2-(3-eth yl-2-m eth yl-
-bu ten yl)-1,3,2-d ioxa bor ola n e (11). Butyllithium (1.6 M
2
H35BO (M ) 318.2730, found 318.2742.
B. Via Tr is(2-br om obu ten yl)bor a n e. Butyne gas (5.9
[
g, 116 mmol) was condensed at -78 °C in a flask equipped
with a dry ice condenser and magnetic stir bar. (The receiver
was weighed before and after the introduction of the butyne.)
Boron tribromide (9.7 g, 3.6 mL, 38 mmol) was cooled to 0 °C
and then added dropwise down the side of the flask over a 5
min period. (Faster addition resulted in loss of butyne due to
the exothermic reaction.) The dry ice condenser was kept
charged while the mixture was allowed to warm to 25 °C over
a period of 4 h. The tris(2-bromobutenyl)borane appeared 95%
3
in hexane, 40 mL, 64 mmol) was added slowly from a syringe
to a stirred solution of chloroiodomethane (21.16 g, 8.73 mL,
1
1
20 mmol) and [4R-[2(R*),4R,5â]]-4,5-dicyclohexyl-2-(2-ethyl-
-methyl-2-propenyl)-1,3,2-dioxaborolane (10) (17.8 g, 56 mmol)
1
9
in THF (200 mL) cooled with a -78 °C bath. The bath was
allowed to warm to 20-25 °C, and the mixture was stirred
for 24 h. The solution was concentrated under vacuum, and
the residue was worked up in the usual way with ether and
saturated aqueous ammonium chloride (see the preparation
1
1
pure by H NMR analysis: 14.5 g (95%); 300 MHz H NMR
(CDCl
CDCl
3
) δ 1.18 (t, 3), 2.61 (dq, 2), 6.78 (t, 1); 75 MHz 13C NMR
) δ 13.3, 39.4, 131.2 (br, B-C), 145.2. The tris(2-
of 9). Concentration of the organic phase yielded liquid 11
(
3
1
(
17.6 g, 95%): 300 MHz H NMR (CDCl
3
) δ 0.89-1.77 (m, 30),
bromobutenyl)borane was dissolved in pentane (300 mL), and
glacial acetic acid (100 mL, 1.4 mol) was added slowly, causing
an exothermic reaction. After the mixture was stirred over-
night, the acid was neutralized with excess sodium carbonate
solution. The pentane phase was separated, dried over
anhydrous magnesium sulfate, and filtered. Pentane was
distilled at atmospheric pressure at a bath temperature up to
2
(
2
C
.03-2.06 (m, 2), 2.39 (m, 1), 3.80-3.85 (m, 2), 4.63 (d, 1), 4.72
d, 1); 75 MHz 13C NMR (CDCl
) δ 12.2, 17.9, 22.7, 25.8, 25.9,
6.3, 27.2, 28.3, 35.7, 42.9, 82.1, 105.0, 157.6; HRMS calcd for
3
+
21
H
37BClO
2
(M ) 332.2889, found 332.2881.
[
4R-[2(S*,S*),4r,5â]]-4,5-Dicycloh exyl-2-(1-ch lor o-5-eth yl-
4
-m eth yl-4-p en ten yl)-1,3,2-d ioxa bor ola n e. A solution of
[4R-[2(S*),4R,5â]]-4,5-dicyclohexyl-2-(3-ethyl-2-methyl-3-bute-
5
5 °C, and 2-bromo-1-butene was distilled into a dry ice cooled
nyl)-1,3,2-dioxaborolane (11) (14.9 g, 45 mmol) in THF (50 mL)
was added via cannula to (dichloromethyl)lithium (50 mmol)
at -100 °C as described for the preparation of 9. Anhydrous
zinc chloride (6.13 g, 45 mmol) was added, the bath was
allowed to warm to 20-25 °C, and the mixture was stirred
for 24 h. The usual workup procedure yielded liquid [4R-
receiver under vacuum, 12.5 g (80%).
[
4R-(4r,5â)]-4,5-Dicycloh exyl-2-m eth yl-1,3,2-dioxa bor o-
la n e. This compound was prepared from [(R)-(R*,R*)]-1,2-
dicyclohexyl-1,2-ethanediol and trimethylboroxine by the pre-
1
8
viously reported method.
[
4R-[2(S*),4r,5â]]-4,5-Dicycloh exyl-2-(1-ch lor oet h yl)-
[
2(S*,S*),4R,5â]]-4,5-dicyclohexyl-2-(1-chloro-5-ethyl-4-methyl-
1
,3,2-d ioxa b or ola n e (9). The previously described proce-
dure
1
4
-pentenyl)-1,3,2-dioxaborolane (16.5 g, 97%): 300 MHz
NMR (CDCl ) δ 0.80-2.09 (m, 32), 2.52-2.55 (m, 1), 3.48 (dd,
), 3.92 (m, 2), 4.79 (m, 2); 75 MHz 13C NMR (CDCl
H
5
a,b
was used for the preparation of (dichloromethyl)-
3
lithium (76 mmol) from a solution of dichloromethane (12.9 g,
1
2
3
) δ 12.2,
0.5, 25.5, 25.8, 25.9, 26.3, 27.2, 28.1, 37.7, 39.5, 42.9, 84.1,
(
17) Masamune, S.; Choy, W.; Kerdesky, F. A. J .; Imperiali, B. J .
Am. Chem. Soc. 1981, 103, 1566-1568.
18) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1994, 59, 5734-
741.
(
(19) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687-
1689.
5

Synthesis of Serricornin via Boronic Esters
J . Org. Chem., Vol. 63, No. 13, 1998 4469
+
1
08.2, 153.8; HRMS calcd for C22
found 380.2629.
4R-[2(S*,S*),4r,5â]]-4,5-Dicycloh exyl-2-(4-et h yl-1,3-
H
38BClO
2
(M ) 380.2653,
ether (100 mL) was added, and the ether phase was washed
with water, dried over magnesium sulfate, and filtered.
Concentration at 50 Torr yielded a residue consisting of
[S-(R*,R*,R*)]-2-ethyl-3,5-dimethyl-1-octen-6-ol (14) and [(R)-
(R*,R*)]-1,2-dicyclohexyl-1,2-ethanediol. The latter was re-
covered by addition of pentane (25 mL) and crystallization at
0 °C. Distillation at 45 °C (0.1 Torr) followed by chromatog-
raphy on silica with 9:1 pentane/ether yielded pure 14 (1.62
[
d im eth yl-4-p en ten yl)-1,3,2-d ioxa bor ola n e (12). Methyl-
magnesium bromide (3.0 M in ether, 13.3 mL, 40 mmol) was
added to a stirred solution of [4R-[2(S*,S*),4R,5â]]-4,5-dicy-
clohexyl-2-(1-chloro-5-ethyl-4-methyl-4-pentenyl)-1,3,2-diox-
aborolane (15.2 g, 40 mmol) in THF (250 mL) at -78 °C over
a period of 20 min. The bath was allowed to warm to 20-25
2
2
1
g, 89%): [R] 546 -12.5 (c ) 2.3, CHCl
(CDCl ) δ 0.83-2.30 (m, 20), 3.4 (m, 1), 4.75 (d, 2); 75 MHz
C NMR (CDCl ) δ 10.9, 12.5, 13.4, 20.2, 26.2, 27.8, 35.7, 37.9,
39.9, 75.9, 106.8, 156.6; HRMS calcd for C12 25O (M + 1)
24O: C,
3
); 300 MHz H NMR
°
C, and the reaction mixture was stirred for 20 h. The usual
3
1
13
workup procedure led to liquid 12 (13.8 g, 96%): 300 MHz H
NMR (CDCl
3
3
) δ 0.84-2.27 (m, 37), 3.81 (m, 2), 4.68 and 4.70
H
1
3
(AB, 2); 75 MHz C NMR (CDCl
3
) δ 12.3, 16.2, 20.2, 25.9, 26.0,
185.1905, found (CI) 185.1893. Anal. Calcd for C12
78.20; H, 13.12. Found: C, 78.02; H, 12.83.
H
2
6.4, 27.4, 28.28, 28.34, 39.2, 39.5, 43.0, 83.2, 106.7, 156.2);
+
HRMS calcd for C23
H
41BO
2
(M ) 360.3200, found 360.3199.
4R-[2(S*,S*,S*),4r,5â]]-4,5-Dicycloh exyl-2-(1-ch lor o-5-
Ser r icor n in (1 + 2). Osmium tetraoxide (80 mg, 0.3 mmol)
was added to a solution of [S-(R*,R*,R*)]-2-ethyl-3,5-dimethyl-
1-octen-6-ol (14) (0.552 g, 3 mmol) in 36 mL of 1,4-dioxane and
12 mL of water at 20-25 °C. After 15 min, finely powdered
sodium periodate (10.0 g, 46.8 mmol) was added in several
portions over a period of 1 h, in accordance with the literature
procedure.20 The mixture was stirred for 16 h and then
extracted with ether. The ether solution was washed with
sodium sulfite solution, dried over anhydrous magnesium
sulfate, filtered, and concentrated at 50 Torr to yield a residue
of serricornin (1 and 2) (0.507 g, 91%). The NMR data are
[
eth yl-2,4-d im eth yl-5-h exen yl)-1,3,2-d ioxa bor ola n e. A so-
lution of [4R-[2(S*,S*),4R,5â]]-4,5-dicyclohexyl-2-(4-ethyl-1,3-
dimethyl-4-pentenyl)-1,3,2-dioxaborolane (12) (13.66 g, 37.94
mmol) in THF (50 mL) was added via cannula to (dichloro-
methyl)lithium (48 mmol) at -100 °C as described for the
preparation of 9. Anhydrous zinc chloride (5.2 g, 38 mmol)
was added, the bath was allowed to warm to 20-25 °C, and
the mixture was stirred for 24 h. The usual workup led to
liquid [4R-[2(S*,S*,S*),4R,5â]]-4,5-dicyclohexyl-2-(1-chloro-5-
2
1
ethyl-2,4-dimethyl-5-hexenyl)-1,3,2-dioxaborolane (15.17 g,
consistent with those previously reported: 300 MHz H NMR
1
2
9
(
(
3
8%): 300 MHz H NMR (CDCl
3
) δ 0.85-2.22 (m, 37), 3.45
(C
(lit. 3.17) (m, 0.75, CHO of 2), 3.75 (lit 3.82) (ddd, 0.25, CHO
of 1); 75 MHz 13C NMR (C
) assigned to 1, δ 8.0, 10.7, 14.0,
6 6
D ) (literature data in parentheses) δ 0.8-2.4 (m, 23), 3.2
1
3
d, 1), 3.93 (m, 2), 4.70 and 4.74 (AB, 2); 75 MHz C NMR
CDCl ) δ 12.3, 17.1, 19.7, 25.3, 25.9, 25.9, 26.3, 27.3, 28.2,
4.2, 37.5, 40.3, 42.9, 84.0, 107.1, 156.1; HRMS calcd for C24
3
6 6
D
H
42
-
16.5, 27.0, 33.9, 36.1, 36.8, 43.6, 76.4, 213.4 (8.0, 10.8, 13.7,
16.4, 27.5, 33.9, 35.8, 36.8, 43.8, 76.4, 213.6); assigned to 2,
7.4, 10.7, 11.7, 16.8, 26.2, 30.2, 31.3, 33.1, 36.1, 72.6, 98.5 (7.4,
+
2
BClO (M ) 408.2966, found 408.2968.
[
4R-[2(S*,S*,S*),4r,5â]]-4,5-Dicycloh exyl-2-(1,5-d ieth yl-
,4-d im eth yl-5-h exen yl)-1,3,2-d ioxa bor ola n e (13). Ethyl-
magnesium bromide (3.0 M in diethyl ether, 35.6 mmol) was
added dropwise over 20 min to a stirred solution of [4R-
2
10.7, 11.7, 16.7, 26.2, 30.2, 31.3, 33.1, 36.2, 72.7, 98.6); HRMS
+
calcd for C11
H
20O [(M - 18) ] 168.1514, found 168.1506.
[
2(S*,S*,S*),4R,5â]]-4,5-dicyclohexyl-2-(1-chloro-5-ethyl-2,4-
Ack n ow led gm en t. We thank the Washington Tech-
nology Center (Seattle, WA) and the National Science
Foundation, Grant No. CHE9613857, for support.
dimethyl-5-hexenyl)-1,3,2-dioxaborolane (14.5 g, 35.6 mmol)
in THF (200 mL) cooled with a -78 °C bath. The bath was
allowed to warm to 20-25 °C, and the mixture was stirred
for 24 h. The usual workup yielded liquid 13 (12.9 g, 90%):
Su p p or tin g In for m a tion Ava ila ble: Copies of the 300
1
3
4
1
3
00 MHz H NMR (CDCl
3
) δ 0.87-2.27 (m, 43), 3.81 (m, 2),
) δ 12.3, 14.1,
7.6, 19.5, 22.0, 25.8, 25.9, 26.1, 27.1, 27.6, 28.2, 28.5, 31.6,
7.4, 43.1, 83.1, 105.8, 156.8; HRMS calcd for C26 [(M
1
13
MHz H and 75 MHz C NMR spectra for compounds 7-14,
.66 and 4.71 (AB, 2); 75 MHz 13C NMR (CDCl
3
the (R-chloroalkyl)boronic ester intermediates between 11 and
2 and between 12 and 13, and the 1H spectrum of 1 (in
1
H
48BO
2
equilibrium with 2) (21 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.
+
+
1) ] 403.3747, found 403.3732.
S-(R*,R*,R*)]-2-E t h yl-3,5-d im et h yl-1-oct en -6-ol (14).
Aqueous 3 M sodium hydroxide (30 mL) and a solution of [4R-
2(S*,S*,S*),4R,5â]]-4,5-dicyclohexyl-2-(1,5-diethyl-2,4-dimethyl-
-hexenyl)-1,3,2-dioxaborolane (13) (4.02 g, 10 mmol) in diethyl
[
[
5
J O980432G
ether (200 mL) were stirred and cooled with an ice bath during
the portionwise addition of 30% hydrogen peroxide (30 mL)
over a period of 1 h. The mixture was stirred for 15 h, more
(
20) Pappo, R.; Allen, D. S., J r.; Lemieux, R. U.; J ohnson, W. S. J .
Org. Chem. 1956, 21, 478-479.