1,4-asymmetric induction in the chromium(II)- and indium-mediated coupling of allyl bromides to aldehydes

Article abstract of DOI:10.1021/jo960986o

A series of allyl bromides bearing an ethereal stereogenic substituent at C-2 were synthesized from methyl acrylate. These were coupled with a range of aldehydes under chromium(II) chloride-mediated conditions to afford syn-4-alkoxyalkan-1-ols in good yie

Full text of DOI:10.1021/jo960986o

6936
J . Org. Chem. 1996, 61, 6936-6940
1,4-Asym m etr ic In d u ction in th e Ch r om iu m (II)- a n d
In d iu m -Med ia ted Cou p lin g of Allyl Br om id es to Ald eh yd es
Robert J . Maguire, J ohann Mulzer,* and J an W. Bats†
Institut fu¨r Organische Chemie, J . W. Goethe-Universita¨t Frankfurt, Marie-Curie-Strasse 11,
D-60439 Frankfurt am Main, Germany
Received May 28, 1996X
A series of allyl bromides bearing an ethereal stereogenic substituent at C-2 were synthesized from
methyl acrylate. These were coupled with a range of aldehydes under chromium(II) chloride-
mediated conditions to afford syn-4-alkoxyalkan-1-ols in good yield and diastereoselectivity. The
effect of altering the nature of the ethereal group and alkyl substituent upon the diastereoselectivity
of the reaction was also investigated. The relative stereochemistry was proved by X-ray structure
analysis. The work was extended to replace the chromium(II) chloride with indium metal, and
this also afforded syn-4-alkoxyalkan-1-ols in good yield and diastereoselectivity.
Sch em e 1
In tr od u ction
Since the initial description of the chromium(II) chloride-
mediated coupling of allyl halides to aldehydes in the late
1970s,1 the “Nozaki-Hiyama” reaction and its variations
have proved to be powerful synthetic operations.2 The
reaction features almost exclusive 1,2-anti-diastereose-
lectivity, excellent chemoselectivity, and the mild Lewis
acidity of the chromium(II) species allows the process to
be performed on relatively sensitive substrates. These
advantages have been demonstrated in the synthesis of
a wide range of natural products.3 Further work in this
field has led to the development of 1,2-asymmetric
induction reactions, either by the use of chiral aldehydes4
or chiral allyl bromides,5 but little attention has been paid
to extending the range of the stereochemical communica-
tion in this reaction. This paper describes a general
method for achieving 1,4-asymmetric induction in the
Nozaki-Hiyama reaction and efforts to optimize the
stereochemical outcome of the reaction. This approach
was extended, in a similar manner, to indium metal as
the coupling agent.
aldehyde to a cyclic allyl iodide.8 In these reports, the
diastereoselectivity is postulated to arise from chelation
between a chiral oxygenated function and the Lewis
acidic element, which then dictates the facial selectivity
of the reaction between the activated allyl species and
the aldehyde. We decided to adopt a similar approach
and to take advantage of the strong affinity of chromium
toward oxygen. The allyl bromides were readily acces-
sible in racemic form in a four-step sequence from methyl
acrylate (1), Scheme 1. Thus, methyl acrylate was
treated with the required aldehyde in the presence of
DABCO according to literature procedure.9 The hydroxy
esters 2a -c were then protected as either a benzyl ether
(3a,d,j),10 tert-butyldimethylsilyl ether (3b,e,h ),11 or meth-
oxymethyl ether (3c,f,i).12 Reduction at low temperature
with DIBAL-H, followed by the Nicolaou bromination of
the resulting alcohols,13 afforded the requisite 2-substi-
tuted allyl bromides 4, which, due to their lability, were
Resu lts a n d Discu ssion
Initial studies in the use of allylmetallic reagents for
1,4-asymmetric induction have been limited to the use
of allylsilanes6 and allylstannanes7 and one specific
example of a chromium(II)-mediated coupling of an
† X-ray structural analysis.
X Abstract published in Advance ACS Abstracts, September 1, 1996.
(1) (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J . Am. Chem.
Soc. 1977, 99, 3179. (b) Buse, C. T.; Heathcock, C. H. Tetrahedron Lett.
1978, 1685. Hiyama, T.; Okude, Y.; Kimura, K.; Nozaki, H. Bull. Chem.
Soc. J pn. 1982, 55, 561.
(2) For recent reviews see (a) Cintas, P. Synthesis 1992, 248. (b)
Hashmi, A. S. K. J . Prakt. Chem. 1996, 338, 491.
(3) e.g. (a) Mulzer, J .; Kattner, L. Angew. Chem., Int. Ed. Engl. 1990,
29, 679. (b) Shibuya, H.; Ohashi, K.; Kawashima, K.; Hori, K.;
Murakami, N.; Kitigawa, I. Chem. Lett. 1986, 85. (c) Rayner, C. M.;
Astles, P. C.; Paquette, L. A. J . Am. Chem. Soc. 1992, 114, 3926. (d)
Still, W. C.; Mobilio, D. J . Org. Chem. 1983, 48, 4785.
(4) Mulzer, J .; Kattner, L., Strecker A. R.; Schro¨der, C.; Buschmann,
J .; Lehmann, C.; Luger, P. J . Am. Chem. Soc. 1991, 113, 4218.
(5) Mulzer, J .; Schulze, T.; Strecker, A.; Denzer, W. J . Org. Chem.
1988, 53, 4908.
(8) Hatakeyama, S.; Numata, H.; Osani, K.; Takano, S. J . Org.
Chem. 1989, 54, 3515.
(9) Hoffmann, H. M. R.; Rabe, J . Angew. Chem., Int. Ed. Engl. 1983,
22, 795.
(10) Wessel, H.-P.; Iversen, T.; Bundle, D. R. J . Chem. Soc., Perkin
Trans. 1 1985, 2247.
(6) Nishigaichi, Y.; Takuwa, A.; J odai, A. Tetrahedron Lett. 1991,
32, 2383.
(7) (a) Nishigaichi, Y.; Kuramoto, H.; Takuwa, A. Tetrahedron Lett.
1995, 36, 3353. (b) Gruttadauria, M.; Thomas, E. J . J . Chem. Soc.,
Chem. Commun. 1995, 1469.
(11) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(12) Stork, G.; Takahashi, T. J . Am. Chem. Soc. 1977, 99, 1275.
(13) Nicolaou, K. C.; Veale, C. A.; Webber, S. E.; Katerinopoulos,
H. J . Am. Chem. Soc. 1985, 107, 7515.
S0022-3263(96)00986-3 CCC: $12.00 © 1996 American Chemical Society

Coupling of Allyl Bromides to Aldehydes
J . Org. Chem., Vol. 61, No. 20, 1996 6937
Sch em e 2
Ta ble 1
ally
bromide
compound
entry
R
PG
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
TBDMS
TBDMS
TBDMS
MOM
MOM
MOM
R′
% yield
syn:antia
no.b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
4a
4a
4a
4a
4a
4a
4a
4d
4d
4d
4g
4g
4g
4b
4e
4h
4c
4f
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Me
Et
64
75
68
71
87:13
83:17
85:15
81:19
81:19
85:15
mixture
91:9
85:15
87:13
95:5
91:9
91:9
83:17
89:11
90:10
81:19
83:17
88:12
5
6
7
8
9
10
-
11
12
13
14
15
16
17
18
19
20
21
22
iPr
tBu
vinyl
CO2Et
Ph
69
26c
complex
71
Ph
Ph
Et
70
68
60
iPr
Ph
iPr
iPr
iPr
Me
Ph
Et
66
iPr
Ph
Ph
Ph
Ph
51d
34
75
64
61
75
iPr
Me
Ph
Ph
Ph
4i
iPr
72
a
1
b
Determined by H NMR. Refers to compound number in experimental section; c: 47% allyl chloride returned; d: 34% allyl chloride
returned.
Sch em e 3
not further characterized, but used directly in the
chromium-mediated coupling reaction.
With a reliable route to the allyl bromides in hand,
attention was turned to attempting the chromium-
mediated coupling reactions. Early work showed that
reactions of allyl bromide 4a with benzaldehyde, per-
formed in THF, afforded a degree of diastereoselectivity,
but were complicated by an Oppenauer-type oxidation
of the product homoallylic alcohol.14 Fortunately, the
formation of the ketone was completely suppressed when
the reaction was performed in DMF, and superior yields
and selectivities were obtained, see Scheme 2 and Table
1. Further studies showed that the optimum tempera-
ture for performing the reactions was -20 °C; below this,
the reaction became sluggish and afforded little improve-
ment in selectivity. Difficulties in isolating the product,
attributed to hydrolysis of the strong chromium-oxygen
bond, were overcome by adopting the procedure of Takai
and Utimoto.15 A range of aldehydes were reacted with
4a under these conditions and afforded homoallylic
alcohols in good yield and selectivity; the results are
presented in Table 1 (entries 1-7). It is notable that
pivalaldehyde (entry 5) gave a high degree of selectivity,
despite being notorious for performing badly in Nozaki-
Hiyama reactions. Less stable aldehydes (entries 6 and
7) decomposed before coupling, maybe this is due to the
long reaction time under Lewis acid conditions. The
reaction also returned significant quantities (ca. 10-25%)
of bromide/chloride exchange product, which unfortu-
nately did not react under these conditions. This problem
is ameliorated by the potential to “recycle” the allyl
chloride species by halide exchange.
The major and minor isomers could be clearly distin-
guished by H-NMR. In all cases, the carbinol proton
1
signal for the major product appeared downfield (ca. 0.1-
0.2 ppm) of the corresponding signal for the minor isomer.
The diastereoisomers could also be differentiated by the
chemical shift and coupling patterns of the allylic and
vinylic protons. The relative configuration of the major
diastereoisomer was determined to be 1,4-syn by X-ray
analysis of 4-phenylbenzoate derivative 24, furnished
from a homoenantiomeric synthesis of allyl bromide 4a ,
Scheme 3. Thus, using literature procedures, (S)-ethyl
lactate was protected using the Bundle procedure10 and
the ester function converted to a methyl ketone (23) via
the method outlined by Weinreb.16 Formation of the enol
triflate,17 followed by palladium(II) acetate catalyzed
(14) Maguire, R. J .; Mulzer, J .; Bats, J . W. Tetrahedron Lett. 1996,
37, 5487.
(15) Fujimura, O.; Takai, K.; Utimoto, K. J . Org. Chem. 1990, 55,
1705.
(16) (a) Levin, J . I.; Turos, E.; Weinreb, S. M. Synth. Commun. 1982,
12, 989. (b) Paterson, I.; Wallace, D. J .; Vela´quez, S. M. Tetrahedron
Lett. 1994, 35, 9083. (c) Nahm, S.; Weinreb, S. M. Tetrahedron Lett.
1981, 22, 3815.

6938 J . Org. Chem., Vol. 61, No. 20, 1996
Maguire et al.
methoxycarbonylation,18 furnished homoenantiomeric es-
ter 3a in good overall yield, which then led through to
the required allyl bromide. Hence, reaction with benz-
aldehyde afforded a mixture of C-1 epimers which could
be separated by bench-top chromatography and acylated
with 4-phenylbenzoyl chloride.19 The benzoate derivative
of the major product 24 crystallized as colorless needles
and allowed its structure to be determined by single
crystal X-ray analysis (supporting information). Unfor-
tunately, the derivative of the minor isomer 25 did not
prove to be so obliging.
Having established the stereochemical outcome of the
reaction, we proceeded to determine the effect of altering
the alkyl residue and ethereal protecting group. Substi-
tuting the methyl group of the allyl bromide with either
phenyl (4d ) or isopropyl (4g) produced a profound effect
on the level of asymmetric induction (entries 8-13),
affording consistently superior diastereoselectivities in
the range 74-82% de and 82-90% de, respectively.
These results draw the conclusion that the steric de-
mands of the allyl bromide far outweigh those of the
aldehyde in determining the level of 1,4-asymmetric
induction furnished by the reaction. The use of allyl
bromides (4b,e,h and 4c,f,i) provided information about
the effect of the ethereal protecting group on the product
profile (entries 14-19). The tert-butyldimethylsilyl- and
methoxymethyl-protecting groups were chosen to alter
the “accessibility” of the oxygen atom, either reducing or
enhancing any interaction it may have with the chro-
mium species. Neither group had any effect in improving
the level of stereoselectivity and actually led to reduced
values, particularly in the case of the methoxymethyl
group. If chromium-oxygen chelation was an important
factor in determining the reaction diastereoselection, it
would be expected that the MOM group would improve
the selectivity and the silyl group reduce it; this is not
the case, and it could well be that the ethereal oxygen
cannot compete with the DMF solvent molecules in
chelating to the chromium species.
After establishing the results of the chromium(II)
chloride reactions, we turned our attention to developing
an alternative coupling system. In recent times, the
metal indium has begun to sparkle in the limelight of
organometallic chemistry, affording such advantages as
low toxicity of the metal and its salts, reactions that can
be performed in “wet” conditions, and the relative ease
of product purifiction.20 Contemporary work by Paquette
and Mitzel, using R- and -oxygenated aldehydes afforded
useful levels of 1,2- and 1,3-asymmetric induction, re-
spectively,21 and this led to our investigation into whether
the variety of allyl bromide species we have developed,
bearing a stereogenic ether function, will provide asym-
metric induction under similar conditions. To our de-
light, exposing allyl bromide 4a to benzaldehyde in the
presence of indium, in THF/water mix, afforded the 1,4-
syn-adduct 5 as the major product. Further experimen-
tation showed that the yield and reaction rate could be
Sch em e 4
Ta ble 2
% yield
allyl
bromide
R
PG
Bn
syn:antia
refb
4a
4d
4g
4b
4e
4h
4c
4f
Me
Ph
iPr
Me
Ph
iPr
Me
Ph
iPr
72
79
59
67
75
71
89
83
85
86:14
88:12
96:4
86:14
90:10
97:3
73:27
79:21
82:18
5
11
14
17
18
19
20
21
22
Bn
Bn
TBDMS
TBDMS
TBDMS
MOM
MOM
MOM
4i
Determined by 1H NMR. b Compound number in Experimental
a
Section.
improved by the addition of tetra-n-butylammonium
iodide, probably through in situ generation of the more
reactive allyl iodide species (the addition of tetraethyl-
ammonium bromide gave little improvement to the
system without added phase-transfer agents). Thus,
taking advantage of our supply of allyl bromides, we
investigated the effect of protecting group and allylic
substituent on the product profile, Scheme 4 and Table
2.
The reactions were generally complete after 8 h, but
some cases (PG ) TBDMS) required stirring overnight.
In these extended reactions, the indium showed a ten-
dency to coagulate into small balls, due to the action of
the stirrer bar; the addition of a small quantity of indium
powder (ca. 0.1-0.2 equiv) to the reaction helped the
reaction to completion. As can be seen from the table,
the results are comparable to those found for the Nozaki-
Hiyama conditions, furnishing similar levels of 1,4-
asymmetric induction and generally better yields. In one
i
system (R ) Pr, PG ) TBDMS), the product diastereo-
selection proved to be superb, emphasizing the steric
demands of the hydrocarbocarbon substituent on the
reaction selectivity.
Mech a n istic Ra tion a le
The stereochemical outcome of the coupling reactions
can be rationalized by considering the approach of the
aldehyde to the preferred conformation of the allyl
bromide function, Scheme 5. Whether it is an aldehyde-
metal complex reacting with the allyl bromide function,
or the aldehyde reacting with an allylmetal species, is
open to debate (hence the use of “M” in the Scheme 5),
but the approach of the carbonyl species is postulated to
occur in a manner antiperiplanar to the oxygenated
function, drawing an analogy to the Felkin-Anh model.3a
The allyl species prefers to adopt the conformation shown
in 26 rather than 27, where the 1,3-allylic strain with
the allylic hydrocarbon residue is minimized and the
steric interaction with the “incoming” aldehyde is also
reduced (R vs H). The facial selection with respect to
the aldehyde is determined by the aldehyde residue (R′)
to reside in the least sterically demanding position, away
from the substituted allylic carbon. A metallo-ene reac-
tion then proceeds via a six-membered chairlike transi-
(17) McMurry, J . E.; Scott, W. J . Tetrahedron Lett. 1983, 24, 979.
(18) Cacchi, S.; Morera, E.; Ortar, O. Tetrahedron Lett. 1985, 26,
1109.
(19) Corey, E. J .; Albonico, S. M.; Koelikker, U.; Schaaf, T. K.;
Varma, R. K. J . Am. Chem. Soc. 1971, 93, 1491.
(20) Li, C.-J . Chem. Rev. 1993, 93, 2023 and references cited therein.
(b) Chan, T.-H.; Li, C.-J .; Lee, M. C.; Wei, Z. Y. Can. J . Chem. 1994,
72, 1181. (c) Prenner, R. H.; Binder, W. H.; Schmid, W. Liebigs Ann.
Chem. 1994, 73. (d) Binder, W. H.; Prenner, R. H.; Schmid, W.
Tetrahedron 1994, 50, 749.
(21) Paquette, L. A.; Mitzel, T. M. J . Am. Chem. Soc. 1996, 118,
1931.

Coupling of Allyl Bromides to Aldehydes
J . Org. Chem., Vol. 61, No. 20, 1996 6939
Sch em e 5
was filtered, the filter cake was washed with ethyl acetate,
and the combined filtrates were concentrated at reduced
pressure. Chromatography on silica gel, using hexane-ethyl
acetate (3:1) as eluent, afforded (3RS)-3-(benzyloxy)-2-meth-
ylidene-1-butanol as a colorless oil (13.15 g, 90%).
Typ ica l P r oced u r e for Br om in a tion Rea ction s. To a
solution of (3RS)-3-(benzyloxy)-2-methylidene-1-butanol (2.14
g, 11.1 mmol) in dry CH2Cl2 (24 mL) at -18 °C were added
portionwise triphenylphosphine (3.36 g, 12.8 mmol) and N-
bromosuccinimide (2.08 g, 11.7 mmol) and stirring was main-
tained at -18 °C for 5 h. To this were added diethyl ether
(50 mL) and water (50 mL), and the mixture was partitioned.
The organic phase was washed with brine, dried (Na2SO4), and
preabsorbed onto silica at reduced pressure. Chromatography
on silica gel, using hexane-ethyl acetate (30:1) as eluent,
afforded (3RS)-3-(benzyloxy)-1-bromo-2-methylidenebutane (4a)
as a colorless oil (1.99 g, 70%).
Typ ica l P r oced u r e for Ch r om iu m (II) Ch lor id e-Med i-
a ted Cou p lin g Rea ction s. To a suspension of chromium-
(III) chloride (0.402 g, 2.54 mmol) in dry THF (10 mL) at 0 °C
was added dropwise lithium aluminum hydride solution (1.27
mL, 1 M in THF, 1.27 mmol), and the mixture was allowed to
warm to ambient temperature and stirred for 30 min. The
THF was evaporated by gently warming the solution in a
stream of argon and replaced by dry DMF (10 mL). The
suspension was cooled to -20 °C, and benzaldehyde (0.138 mL,
1.36 mmol) was added dropwise followed by a solution of (3RS)-
1-bromo-3-(methoxymethoxy)-3-phenyl-2-methylidenepro-
pane (4f) (0.246 g, 0.91 mmol) in dry DMF (2 mL). The
solution was stirred at -20 °C for 18 h and then poured into
a rapidly stirred mixture of water (20 mL), brine (20 mL), and
diethyl ether (20 mL), with a wash of ethyl acetate (20 mL),
and stirred at ambient temperature for 48 h. The mixture
was extracted with diethyl ether (×3), and the combined
organic extracts were washed with brine, dried (Na2SO4), and
concentrated at reduced pressure. Chromatography on silica
gel, using hexane-diethyl ether (8:1) as eluent, afforded (1RS,
4SR)-1,4-diphenyl-4-(methoxymethoxy)-3-methylidene-1-bu-
tanol (21) as a mixture of diastereoisomers (0.202 g, 75%).
The major and minor diastereoisomers could be partially
separated by further bench-top chromatography. The analyti-
cal data for the syn diastereomers are presented in the
supporting information.
tion state, in which the aldehyde substituent attains an
equatorial position, to afford the 1,4-syn-product. This
hypothesis is supported by the increase in the bulk of
the allylic hydrocarbon residue (R) furnishes improved
diastereoselectivity, and that little difference in reaction
selectivity is observed by altering the nature of the ether
function, which in this model is essentially removed from
the interaction with the aldehyde.
Con clu sion
To conclude, this paper outlines the development of
long range stereochemical communication techniques in
the Nozaki-Hiyama reaction and investigates the effect
of altering the nature of the controlling stereogenic
center. The reaction affords good to excellent 1,4-syn-
asymmetric induction, comparable to those observed for
the 1,2-diastereoselective reactions.3 This paper also
outlines the first example of 1,4-asymmetric induction
in indium-mediated allyl transfer chemistry, featuring
the stereocontrolling element on the allyl bromide. It is
our hope that this work will receive further attention in
the solution of synthetic problems.
Exp er im en ta l Section
All reagents and solvents were of commercial quality or
purified by literature procedures.22 Chromium(III) chloride
was purchased from Merck, Darmstadt, and dried over P2O5
at reduced pressure overnight. Anhydrous DMF, lithium
aluminum hydride solution in THF, and indium powder (Mg
free) were purchased from Aldrich Chemical Co. All temper-
atures refer to the external bath temperature. Anhydrous
reactions were performed under an atmosphere of argon. The
1H-NMR and 13C-NMR spectra were run in chloroform-d and
measured on 250, 270, 400, or 600 MHz machines.
Typ ica l P r oced u r e for DIBAL-H Rea ction s. Diisobu-
tylaluminum hydride (160 mL, 1 M in hexane) was added
dropwise to a solution of methyl (3RS)-3-(benzyloxy)-2-meth-
ylidenebutanoate (16.71 g, 76 mmol) in dry CH2Cl2 at -78 °C,
and stirring was maintained at -78 °C for 3 h. To this was
added methanol (27 mL), and the solution was allowed to
warm to 0 °C, followed by the dropwise addition of saturated
ammonium chloride solution (81 mL). The mixture was stirred
rapidly for 3 h and then left to stand for 18 h. The mixture
(1R,4S)-4-Ben zyloxy-3-m eth ylid en e-1-p h en yl-1-p en te-
n yl 4-P h en ylben zoa te (24). 4-Phenylbenzoyl chloride (110
mg, 0.51 mmol) was added to a stirred solution of (1R,4S)-4-
(benzyloxy)-3-methylidene-1-phenyl-1-pentanol (9) (57 mg, 0.20
mmol), triethylamine (82 L 0.59 mmol), and DMAP (7 mg,
0.06 mmol) in dry CH2Cl2 (2 mL) at ambient temperature, and
the solution was stirred for 18 h. The mixture was diluted
with diethyl ether and washed with water (×2) and brine,
(22) Perrin, D. D.; Armarego, W. L. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: Oxford, 1993.

6940 J . Org. Chem., Vol. 61, No. 20, 1996
Maguire et al.
dried (MgSO4), and concentrated at reduced pressure. Chro-
matography on silica gel, using hexane-diethyl ether (20:1)
as eluent, afforded the title compound as a colorless oil (75
mg, 80%). Trituration of this oil with n-pentane at 0 °C
afforded fine white crystals. Recrystallization from pentane-
CH2Cl2 afforded colorless needles.
X-r a y Cr yst a llogr a p h ic Da t a of Com p ou n d 24:23
C32H30O3, Mr ) 462.59, orthorhombic, P212121, a ) 6.0796(5),
b ) 14.579(3), c ) 29.305(8) Å, V ) 2597(1) Å3, Z ) 4, Dc )
1.183 g cm-3, linear absorption coeff ) 5.5 cm-1, radiation )
Cu KR, scan mode ) , total no. of reflections ) 3058 at scan
range +h,(k,+l quadrant at rt. 2
wR(F) ) 0.052.
) 100°, R(F) ) 0.052,
max
Mp: 89-91 °C; [R]20D -62.9 (c 0.68, CHCl3); max 3031, 2926,
A single crystal was measured on an ENRAF-NONIUS
CAD4 diffractometer. Three standard reflections remeasured
every 5500 s remained stable. No absorption correction was
made. No averaging of equivalent reflections was performed.
The structure was determined by direct methods using pro-
gram SIR92. The H atoms were placed at calculated positions
and were not refined. The C and O atoms were refined with
anisotropic thermal parameters. The structure was refined
on F values using weighting scheme: w(F) ) 4×F2/[ 2(F2) +
(0.03×F2)2]. The final difference density was between -0.12
and +0.11 e Å-3. A refinement of the Flack parameter gave x
) -0.4(4) (x ) 0 for the correct and 1 for the wrong absolute
structure). The calculations were performed with the SHELX
and MolEN program systems.
1715, 1608, 1268, 1100, 746, 670;
1.34 (3H, d, J ) 6.5), 2.71
H
(1H, dd, J ) 15.2, 5.4), 2.84 (1H, dd, J ) 15.2, 8.7), 3.98 (1H,
q, J ) 6.5), 4.23 and 4.41 (each 1H, d, J ) 12), 5.08 (1H, d, J
) 1.1), 5.13 (1H, s), 6.25 (1H, dd, J ) 8.7, 5.4), 7.29 (9H, m),
7.43 (4H, m), 7.63 (4H, m), 8.13 (2H, m); C 165.5, 145.6, 145.2,
140.5, 139.9, 138.4, 130.0, 129.0, 128.8, 128.4, 128.2, 127.9,
127.5, 127.3, 127.1, 127.0, 126.5, 114.2, 78.2, 75.2, 69.9, 37.4,
20.1. Anal. C32H30O3 (Mr 462.59) Calcd C: 83.09 H: 6.54.
Found C: 82.82 H: 6.72
(1S,4S)-4-Ben zyloxy-3-m eth ylid en e-1-p h en yl-1-p en te-
n yl 4-P h en ylben zoa te (25). The title compound was pre-
pared from (1S,4S)-4-(benzyloxy)-3-methylidene-1-phenyl-1-
pentanol (30 mg, 0.11 mmol) in the manner described above.
This afforded the title compound as an opaque, colorless glass
(45 mg, 92%).
Ack n ow led gm en t. Financial support for the project
was provided through the EC Mobility Network “Allyl-
metals” (contract ERB-CHRX CT94-0620). The authors
would also like to acknowledge the assistance of Dr. G.
Zimmerman in obtaining 1H NMR spectra and M.
Christoph for elemental analysis.
[R]20 +33.1 (c 0.72, CHCl3);
3031, 2926, 1716, 1608,
max
1.30 (3H, d, J ) 6.5), 2.64 (1H,
D
1451, 1267, 1100, 1029, 747;
H
dd, J ) 15.7, 4.8), 2.95 (1H, dd, J ) 15.7, 9.4), 3.95 (1H, q, J
) 6.5), 4.27 and 4.52 (each 1H, d, J ) 12.0), 5.16 (1H, s), 5.18
(1H, s), 6.30 (1H, dd, J ) 9.3, 4.8), 7.33 (9H, m), 7.48 (4H, m),
7.63 (4H, m), 8.12 (2H, m); C 165.5, 145.6, 145.0, 140.5, 139.9,
138.6, 130.0, 128.9, 128.8, 128.4, 128.2, 128.0, 128.0, 127.4,
127.3, 127.1, 127.0, 126.5, 113.9, 78.3, 74.7, 69.9, 37.3, 20.3.
Typ ica l P r oced u r e for th e In d iu m Meta l-Med ia ted
Cou p lin g Rea ction s. Indium metal powder (0.225 g, 1.96
mmol) was added to a rapidly stirred solution of 4c (0.228 g,
1.09 mmol) and tetra-n-butylammonium iodide (0.725 g, 1.96
mmol) in THF (1 mL) and water (1 mL) at ambient temper-
ature. The mixture was stirred rapidly for 8 h, diluted with
ethyl acetate, and preabsorbed onto silica gel at reduced
pressure. The silica powder was washed with diethyl ether
(×3), and the combined filtrates were concentrated at reduced
pressure. Chromatography on silica gel, using hexane-ethyl
acetate (5:1) as eluent, afforded 20 (0.231 g, 89%).
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for 5-22; ORTEP diagram of 24 (6 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.
J O960986O
(23) The authors have deposited full details of the X-ray structure
determination of compound 24 with the Cambridge Crystallographic
Data Centre. These data can be obtained, on request, from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK.