Factors Influencing 1,4-Asymmetric Induction during Indium-Promoted Coupling of Oxygen-Substituted Allylic Bromides to Aldehydes in Aqueous Solution

Article abstract of DOI:10.1021/jo970158a

The preparation and indium-promoted aldehyde addition reactions of a series of 3-substituted 3-oxy1-bromo-2-methylidenepropanes under aqueous conditions are described.The (tert-butyldimethylsilyl)oxy derivatives 4a-d are the most diastereoselective of this group of reagents, giving rise to levels of syn-1,4-asymmetric induction in the range of 87-99percent.Interestingly, syn stereoselectivity is eroded and reactions proceed more rapidly when the steric bulk of the oxygen substituent is reduced as in the hydroxy and methoxy derivatives.This dropoff in ?-facial differentiation with kinetic acceleration is attributed to the operation of chelation effects during oxidative addition of the metal into the carbon-bromine bond, but not during the coupling stage.Once the aldehyde enters into the coordination sphere of the indium, internal chelation to the proximal oxygen is disrupted and conformational restrictions are released.These effects, in combination with the absence of a powerful steric control element in the latter examples, permit competitive passage via syn and anti transition states.

Full text of DOI:10.1021/jo970158a

3370
J . Org. Chem. 1997, 62, 3370-3374
F a ctor s In flu en cin g 1,4-Asym m etr ic In d u ction d u r in g
In d iu m -P r om oted Cou p lin g of Oxygen -Su bstitu ted Allylic
Br om id es to Ald eh yd es in Aqu eou s Solu tion
Leo A. Paquette,* George D. Bennett, Adnan Chhatriwalla,† and Methvin B. Isaac
Evans Chemical Laboratories, Columbus, Ohio 43210
Received J anuary 28, 1997X
The preparation and indium-promoted aldehyde addition reactions of a series of 3-substituted 3-oxy-
1-bromo-2-methylidenepropanes under aqueous conditions are described. The (tert-butyldimeth-
ylsilyl)oxy derivatives 4a -d are the most diastereoselective of this group of reagents, giving rise
to levels of syn-1,4-asymmetric induction in the range of 87-99%. Interestingly, syn stereoselectivity
is eroded and reactions proceed more rapidly when the steric bulk of the oxygen substituent is
reduced as in the hydroxy and methoxy derivatives. This dropoff in π-facial differentiation with
kinetic acceleration is attributed to the operation of chelation effects during oxidative addition of
the metal into the carbon-bromine bond, but not during the coupling stage. Once the aldehyde
enters into the coordination sphere of the indium, internal chelation to the proximal oxygen is
disrupted and conformational restrictions are released. These effects, in combination with the
absence of a powerful steric control element in the latter examples, permit competitive passage
via syn and anti transition states.
The influence on transition-state organization of het-
the relative importance of polar, steric, and chelation
factors in carbon-carbon bond-forming reactions of this
type had not been described at the initiation of our
efforts. Since then, Mulzer and his co-workers have
described closely related studies involving oxygen-
substituted allylic bromides with aldehydes in the pres-
ence of chromium(II) (in DMF-THF at -20 °C) and
indium metal [in THF-H2O (1:1) at 20 °C].7 The work
described below significantly extends this complementary
effort and underscores the possibilities for attaining
reliable 1,4-asymmetric induction in water as the reaction
medium.
eroatom substituents positioned either R or â to carbonyl
groups undergoing nucleophilic attack can be very sub-
stantial. When chelation operates, reaction diastereo-
selection is controlled by intramolecular delivery from the
sterically less hindered π-face of the preformed complex.1-3
In substrates lacking the potential for chelate organiza-
tion, the interplay of steric and electronic forces summed
up in the Felkin-Ahn model4 provides a useful stereoin-
duction paradigm. Recent studies in these laboratories
have addressed the applicability of the above criteria to
indium-mediated coupling reactions in water. When
unprotected hydroxyl groups are involved, reactions are
accelerated as a consequence of effective chelation in the
aqueous environment, and maximum π-facial diastereo-
selectivity is realized.5 A comparable response is elicited
by R-(dimethylamino) groups.6 In other circumstances
involving such carbonyl-flanking substituents as tert-
butyldimethylsiloxy, phenylthio, N,N-dibenzylamino, N-
BOC, and methylthio, slower reaction rates are observed
with different stereoselectivities. Consequently, the more
rapid allylations are the more stereocontrolled processes!
In continuation of our investigation of metal-mediated
coupling reactions in aqueous media, we have presently
examined the consequences of placing different oxygen
substituents on the nucleophilic reaction partner, with
particular focus on the issue of 1,4-asymmetric induction.
In this study, 11 allylic bromides having different coor-
dination potential and steric demands have been reacted
with a triad of aldehydes. The objective of identifying
Resu lts a n d Discu ssion
The functionalized allylic bromides were conveniently
prepared by initial condensation of methyl acrylate with
the aldehyde of choice under Bayliss-Hillman conditions8
(Scheme 1). After conversion to the individual tert-
butyldimethylsilyl ethers,9 the esters 2 were reduced with
Dibal-H in THF at -78 °C and transformed into the
bromides 4 by exposure to N-bromosuccinimide and
triphenylphosphine in CH2Cl2 at low temperature.10 The
unprotected hydroxy bromides 6 were obtained by mild
acidic hydrolysis with p-toluenesulfonic acid monohy-
drate in methanol.11 The O-methylation of hydroxy
esters 1 was effected initially with silver oxide and
methyl iodide12 but proceeded in low yield. Utilization
of an alternative more lengthy sequence starting from 2
made available the bromides 5 with greater efficiency.
At a minimum, the additions were carried out in water
alone as well as in a 1:1 mixture of water and THF. The
† Undergraduate Research Participant, 1996.
X Abstract published in Advance ACS Abstracts, April 15, 1997.
(1) (a) Cram, D. J .; Wilson, D. R. J . Am. Chem. Soc. 1963, 85, 1245.
(b) Cram, D. J .; Kopecky, K. R. J . Am. Chem. Soc. 1959, 81, 2748.
(2) (a) Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1984, 23, 556. (b)
Reetz, M. T. Acc. Chem. Res. 1993, 26, 462.
(7) (a) Maguire, R. J .; Mulzer, J .; Bats, J . W. Tetrahedron Lett. 1996,
37, 5487. (b) Maguire, R. J .; Mulzer, J .; Bats, J . W. J . Org. Chem. 1996,
61, 6936.
(8) (a) Basavaiah, D.; Dharma Rao, P.; Suguna Hyma, R. Tetrahe-
dron 1996, 52, 8001. (b) Ciganek, E. Org. React., submitted for
publication.
(9) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(10) Nicolaou, K. C.; Veale, C. A.; Webber, S. E.; Katerinopoulos,
H. J . Am. Chem. Soc. 1985, 107, 7515.
(3) Ager, D. J .; East, M. B. Tetrahedron 1992, 48, 2803.
(4) (a) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
2199. (b) Anh, N. T. Top. Curr. Chem. 1980, 88, 145.
(5) (a) Paquette, L. A.; Mitzel, T. M. Tetrahedron Lett. 1995, 36,
6863. (b) Paquette, L. A.; Mitzel, T. M. J . Am. Chem. Soc. 1996, 118,
1931. (c) Paquette, L. A.; Lobben, P. C. J . Am. Chem. Soc. 1996, 118,
1917.
(11) Newton, R. F.; Reynolds, D. P.; Finch, M. A. W.; Kelly, D. R.;
Roberts, S. M. Tetrahedron Lett. 1979, 20, 3981.
(12) Finch, N.; Fitt, J . J .; Hsu, I. H. S. J . Org. Chem. 1975, 40, 206.
(6) Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.;
Schomer, W. W. Submitted for publication.
S0022-3263(97)00158-8 CCC: $14.00 © 1997 American Chemical Society

Factors Influencing 1,4-Asymmetric Induction
J . Org. Chem., Vol. 62, No. 10, 1997 3371
Ta ble 1. 1,4-Syn (7):1,4-An ti (8) Ra tios Obser ved for th e In d iu m -Med ia ted Cou p lin g of Oxygen a ted Allylic Br om id es to
Ald eh yd es in Wa ter a n d Oth er Solven t System s (25 °C)a
Sch em e 1
dropoff in yields observed in water is considered to stem
from the quite limited solubility of many of the reactants
in this medium. This was not an issue when an organic
cosolvent was present. Several experiments were also
performed in dry THF in order to observe the conse-
quences of a purely organic environment and to permit
direct comparison. The results are compiled in Table 1.
All product ratios were determined by 300 MHz 1H
NMR analysis of the unpurified product mixtures in
advance of chromatographic separation of the diastere-
omers. Distinction between the 1,4-syn and 1,4-anti
diastereomers (7 and 8, Scheme 2) was readily ac-
complished on several fronts. As the Mulzer group has
convincingly established,7 the chemical shift of the newly
generated carbinol proton invariably appears to lower
field in 7 than in 8. This pattern was observed irrespec-
tive of whether this hydrogen is benzylic or not. The
phenomenon may arise as a direct consequence of in-
tramolecular hydrogen bonding between the two het-
eroatoms, this alignment thrusting the carbinol proton
more deeply into the deshielding π-cloud of the double
bond within the syn isomers. In certain cases, particu-
larly those products from the a series, other protons were
also found to be highly diagnostic of stereochemistry. In
addition, all of the syn isomers were less polar than their
anti counterparts.
Where the TBSO-substituted bromides 4a -d are con-
cerned, attractively high syn stereoselectivity was invari-
ably observed. The coupling reactions involving 4, when
performed in water, were typically somewhat more
diastereoselective than those conducted in the mixed
solvent system. Higher yields were generally noted in
the latter context, especially when improved solubility
was gained by having THF present. The availability of
a free hydroxyl group as in 6 led to increased production
of the anti diastereomer. This trend was little modified
when the methyl ethers 5 were brought into reaction.

3372 J . Org. Chem., Vol. 62, No. 10, 1997
Paquette et al.
Sch em e 2
Sch em e 3
likely reduce energy demands and increase production
of this organometallic intermediate (Scheme 3). Experi-
ments designed to gauge the competitive consumption
of 4c and 6c by indium in water have shown the
difference in rate to be considerable (i.e., >3:1). We
interpret this phenomenon to be general and to be the
root cause of the overall kinetics.
F igu r e 1. Transition state models.
However, the hydroxy bromides 6 did react at signifi-
cantly accelerated rates, and the methoxy systems 5 were
of intermediate reactivity. The coaddition of inorganic
salts such as ammonium chloride and indium tribromide
had little effect on product ratios. No advantage was
gained by performing the couplings in anhydrous THF
where appreciably lower yields were often observed.
These data indicate that the formation of 1,4-syn
products becomes significant only when the steric bulk
of the oxygenated substituent in the allylic bromide is
appreciably increased by formation of the tert-butyldi-
methylsilyl ether. This stereochemical bias is consistent
with intervention of the nonchelated transition state A
depicted in Figure 1 where the overall size of the OTBS
group is controlling. For the hydroxy and methoxy
bromides, it is possible that the erosion of syn-selectivity
occurs because the O-inside conformer B is now reason-
ably populated due to the more closely balanced steric
demands of the R and OR′′ substituents. This interpre-
tation assumes that little if any inherent difference exists
in the reactivity of A and B. However, evidence in
support of the assumption that the product composition
mirrors the approximate population of these conformers
has been difficult to come by.
Notwithstanding, the substantive kinetic acceleration
observed with the hydroxy bromides 6 warrants detailed
consideration. Customarily, increases in reaction rate
have been linked to lowerings in transition-state energies
brought on by preformation of kinetically relevant che-
lated complexes.13 The present context differs from the
norm in that two distinctively different steps comprise
the overall coupling process. The first involves formation
of the allylindium reagent, and the second culminates
in actual carbon-carbon bond formation. It is entirely
likely that the overall rate enhancement is a function of
the rate at which the organoindium reagent is generated.
Formation of a chelate such as 9 during oxidative
addition of the metal into the C-Br bond would very
Approach of an aldehyde to a chelate such as 9 appears
to induce coordination of indium to the carbonyl oxygen
at the expense of the hydroxy (or methoxy) group.
While this process lends itself to activation of the
aldehyde, the stereogenic hydroxyl-substituted carbon is
no longer rigidified in its conformation. Access to 10 and
11 becomes possible, these activated complexes leading
competitively to anti and syn products, respectively.
The contrast between the present study and earlier
investigations involving the allylindation of R-hydroxy
carbonyl compounds is striking. When the hydroxy
substituent resides R or â to the carbonyl, chelation
operates, bond rotation becomes restricted, and high
stereoselectivity accompanies the more rapid reactions.
When the hydroxyl group resides in the allylic bromide,
all of the above factors operate during the metalation
process, but the chelate so formed is disrupted when the
aldehyde is brought into the indium coordination sphere.
As a result, stereoselectivity is decreased and the coupled
product composition comes entirely under steric control.
Since -OTBS is the largest group, it does not engage in
preliminary chelation, but does control the subsequent
coupling diastereoselectivity at a notably high level.
Under these circumstances, the slowest reactions deliver
the highest levels of 1,4-asymmetric induction! Whether
the same sensitive dependencies operate in other contexts
remains to be elucidated. To this end, further studies
in this area are presently being pursued.
Exp er im en ta l Section 14
Bromides 4a -c have been previously reported,7b and their
spectral properties are not documented here.
Gen er a l P r oced u r e for th e Desilyla tion of 4. A solution
of 4c (1.70 g, 5.00 mmol) in methanol was treated with
p-toluenesulfonic acid monohydrate (950 mg, 5.00 mmol),
stirred overnight at rt, and concentrated. The residue was
chromatographed on silica gel (elution with 15% ethyl acetate
in hexanes) to give 840 mg (74%) of 6c as a colorless oil, which
crystallized on standing: mp 40-41 °C; IR (CH2Cl2, cm-1
)
(13) (a) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J . Am.
Chem. Soc. 1990, 112, 6130; 1992, 114, 1778. (b) Frye, S. V.; Eliel, E.
L.; Cloux, R. J . Am. Chem. Soc. 1987, 109, 1862.
(14) For generic experimental details, consult ref 5c.

Factors Influencing 1,4-Asymmetric Induction
J . Org. Chem., Vol. 62, No. 10, 1997 3373
1
3605, 1490, 1450, 1215, 1047; H NMR (300 MHz, CDCl3) δ
g, 12.2 mmol). The reaction mixture was stirred for 2 h,
diluted with ether (65 mL), and allowed to warm to rt prior to
washing with saturated NaHCO3 solution and brine, drying,
and solvent evaporation. Following the addition of pentane
(45 mL), the insoluble solid was removed by filtration, and the
filtrate was concentrated and purified chromatographically
(silica gel, elution with 2% ethyl acetate in hexanes) to give
986 mg (46%) of 5c as a colorless oil: IR (CH2Cl2, cm-1) 1450,
1210, 1097; 1H NMR (300 MHz, CDCl3) δ 7.44-7.30 (m, 5 H),
5.40 (s, 1 H), 5.32 (s, 1 H), 4.94 (s, 1 H), 4.08 (d, J ) 10.6 Hz,
1 H), 3.76 (d, J ) 10.6 Hz, 1 H), 3.37 (s, 3 H); 13C NMR (75
MHz, CDCl3) ppm 145.3, 139.1, 128.9, 128.7, 128.4, 128.0,
127.3, 116.3, 83.0, 57.0, 33.3; MS m/ z (M+) calcd 240.0149,
obsd 240.0133.
7.38-7.32 (m, 5 H), 5.46 (s, 1 H), 5.40 (d, J ) 6.4 Hz, 2 H),
4.02 (d, J ) 10.5 Hz, 1 H), 3.73 (d, J ) 10.5 Hz, 1 H), 2.46 (s,
1 H); 13C NMR (75 MHz, CDCl3) ppm 146.8, 141.0, 128.6, 128.1,
126.8, 115.8, 74.1, 33.1; MS m/ z (M+) calcd 225.9993, obsd
225.9981.
Anal. Calcd for C10H11BrO: C, 53.10; H, 4.90. Found: C,
53.13; H, 4.89.
For 6a : 74% yield; colorless oil; IR (CHCl3, cm-1) 3604, 1219,
1
1093; H NMR (300 MHz, CDCl3) δ 5.30-5.28 (m, 2 H), 4.54
(q, J ) 6.5 Hz, 1 H), 4.53 (d, J ) 10.5 Hz, 1 H), 4.49 (d, J )
10.5 Hz, 1 H), 1.93 (s, 1 H), 1.38 (d, J ) 6.5 Hz, 3 H); 13C NMR
(75 MHz, CDCl3) ppm 148.9, 115.1, 68.1, 32.8, 22.2; MS m/ z
(M+) calcd 163.9864, obsd 163.9887.
5a . The alcohol was obtained in 29% yield as a colorless
Anal. Calcd for C5H9BrO: C, 36.59; H, 5.53. Found: C,
36.46; H, 5.53.
1
oil: IR (CHCl3, cm-1) 3512, 1456, 1376, 1090; H NMR (300
MHz, CDCl3) δ 5.28 (s, 1 H), 5.17 (s, 1 H), 4.21 (d, J ) 13.8
For 6b : 60% yield; colorless oil; IR (CH2Cl2, cm-1) 3620,
1
Hz, 1 H), 4.16 (d, J ) 13.8 Hz, 1 H), 3.87 (q, J ) 6.5 Hz, 1 H),
1465, 1390, 1370, 1213, 1022; H NMR (300 MHz, CDCl3) δ
3.26 (s, 3 H), 1.29 (d, J ) 6.5 Hz, 3 H) (OH not observed); 13
C
5.38 (s, 1 H), 5.30 (s, 1 H), 4.07 (d, J ) 5.5 Hz, 1 H), 4.01 (q,
J ) 10.3 Hz, 2 H), 1.90 (heptet, J ) 6.6 Hz, 1 H), 1.64 (br s, 1
H), 0.95 (d, J ) 6.7 Hz, 3 H), 0.93 (d, J ) 6.6 Hz, 3 H); 13C
NMR (75 MHz, CDCl3) ppm 146.8, 117.1, 78.0, 32.8, 31.5, 19.6,
16.8; MS m/ z (M+ - Br) calcd 113.0966, obsd 113.0923.
NMR (75 MHz, CDCl3) ppm 148.4, 112.4, 79.6, 62.8, 56.1, 19.8;
MS m/ z (M+) calcd 116.0837, obsd 116.0812.
Conversion to bromide 5a in the predescribed manner
proceeded in 62% yield: colorless oil; IR (CHCl3, cm-1) 1210,
1114, 732; 1H NMR (300 MHz, CDCl3) δ 5.36 (s, 1 H), 5.26 (s,
1 H), 4.04 (d, J ) 11.3 Hz, 1 H), 3.95 (q, J ) 6.6 Hz, 1 H), 3.94
(d, J ) 11.3 Hz, 1 H), 3.28 (s, 3 H), 1.32 (d, J ) 6.6 Hz, 3 H);
13C NMR (75 MHz, CDCl3) ppm 146.2, 116.5, 77.6, 56.2, 32.1,
20.1; MS m/ z (M+) calcd 177.9993, obsd 178.0012.
For 6d : 60% yield; colorless oil; IR (CHCl3, cm-1) 3605, 1450,
1
1210, 1020; H NMR (300 MHz, CDCl3) δ 5.36 (s, 1 H), 5.25
(s, 1 H), 4.03 (d, J ) 0.6 Hz, 1 H), 4.02 (d, J ) 15 Hz, 1 H),
4.00 (d, J ) 15 Hz, 1 H), 1.95-1.00 (series of m, 11 H) (OH
not observed); 13C NMR (75 MHz, CDCl3) ppm 146.4, 117.3,
77.6, 41.3, 32.6, 29.8, 27.6, 26.3, 26.1, 25.9; MS m/ z (M+) calcd
232.0462, obsd 232.0470.
Alter n a tive Syn th esis of 5d . To a solution of the alcohol
produced by reduction of 2d (3.60 g, 12.7 mmol) in CH2Cl2 (20
mL) were added ethyl vinyl ether (4.0 g, 56 mmol) and
pyridinium p-toluenesulfonate (5 mg). The mixture was
stirred at rt for 1 h and concentrated in vacuo to leave a
residue that was dissolved in THF (10 mL) and treated with
tetra-n-butylammonium fluoride (25 mL of 1 M in THF, 25
mmol). This solution was diluted with ether, washed with
saturated NH4Cl solution and brine, dried, and concentrated.
The resulting oil was dissolved in THF (5 mL) and added to a
suspension of sodium hydride (206 mg, 8.6 mmol) in THF (5
mL). Following the addition of methyl iodide (1.4 g, 10 mmol),
the mixture was stirred for 5 h, quenched with methanol (2
mL), diluted with ether, washed with water, and concentrated.
The residue was treated with a 1:1 mixture of acetic acid and
water (10 mL), stirred for 3 h, and diluted with ethyl acetate
(20 mL). The separated organic phase was washed with brine,
dried, and concentrated. The alcohol was purified by flash
chromatography on silica gel to give 300 mg (13% overall) of
colorless oil: IR (CHCl3, cm-1) 3469, 1450, 1219; 1H NMR (300
MHz, CDCl3) δ 5.26 (dd, J ) 3.1, 1.5 Hz, 1 H), 5.00 (d, J ) 1.0
Hz, 1 H), 4.22 (dt, J ) 14, 1.5 Hz, 1 H), 4.05 (dt, J ) 14, 1.0
Hz, 1 H), 3.25 (s, 3 H), 3.22 (d, J ) 14 Hz, 1 H), 1.90-0.70
(series of m, 11 H); 13C NMR (75 MHz, CDCl3) ppm 145.4,
114.8, 90.5, 63.1 56.8, 40.1, 29.8, 29.4, 26.5, 25.9, 25.8; MS
m/ z (M+) calcd 184.1463, obsd 184.1462.
Anal. Calcd for C10H17BrO: C, 51.52; H, 7.35. Found: C,
51.41; H, 7.32.
Gen er a l P r oced u r e for th e O-Meth yla tion of 1.
A
mixture of 1c (3.84 g, 20.0 mmol), methyl iodide (15.0 g, 100
mmol), and silver(I) oxide (23.2 g, 100 mmol) in acetonitrile
(50 mL) was stirred rapidly in the absence of light for 48 h,
filtered through a Celite pad, and concentrated. The residue
was chromatographed on silica gel (elution with 5% ethyl
acetate in hexanes) to give 3c (1.99 g, 48%) as a colorless oil:
1
IR (CH2Cl2, cm-1) 1724; H NMR (300 MHz, CDCl3) δ 7.41-
7.24 (m, 5 H), 6.34 (s, 1 H), 5.94 (s, 1 H), 5.14 (s, 1 H), 3.70 (s,
3 H), 3.32 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm 166.3, 141.1,
139.5, 132.6, 129.6, 128.3, 127.9, 127.5, 124.9, 81.0, 57.0, 51.8;
MS m/ z (M+) calcd 206.0943, obsd 206.0942.
Anal. Calcd for C12H14O3: C, 69.87; H, 6.85. Found: C,
69.78; H, 6.83.
For 3a : IR (CHCl3, cm-1) 1715, 1450, 1293, 1089; 1H NMR
(300 MHz, CDCl3) δ 6.24 (s, 1 H), 5.81 (s, 1 H), 4.17 (q, J )
6.4 Hz, 1 H), 3.74 (s, 3 H), 3.26 (s, 3 H), 1.26 (d, J ) 6.4 Hz, 3
H); 13C NMR (75 MHz, CDCl3) ppm 166.7, 141.9, 124.1, 75.2,
56.6, 51.7, 21.4; MS m/ z (M+) calcd 144.0786, obsd 144.0781.
Gen er a l P r oced u r e for Diba l-H Red u ction a n d Br o-
m in a tion of 3. A cold (-78 °C), magnetically stirred solution
of 3c (4.21 g, 20.4 mmol) in dry THF (20 mL) was treated
dropwise with Dibal-H (40 mL of 1.0 M in hexanes, 40.0 mmol).
After 1 h at this temperature, saturated Rochelle salt solution
(55 mL) was introduced, and the heterogeneous reaction
mixture was allowed to warm to rt overnight. The separated
aqueous phase was extracted with ethyl acetate (3×), and the
combined organic solutions were washed with brine, dried, and
concentrated. Chromatography of the residue on silica gel
(elution with 10% ethyl acetate in hexanes) furnished 2.30 g
(63%) of alcohol as a faint yellow oil: IR (CH2Cl2, cm-1) 3620,
1494, 1452, 1385, 1190, 1096, 1078; 1H NMR (300 MHz, CDCl3)
δ 7.40-7.22 (m, 5 H), 5.25 (s, 1 H), 5.15 (s, 1 H), 4.80 (s, 1 H),
4.11 (d, J ) 13.5 Hz, 1 H), 3.99 (d, J ) 13.5 Hz, 1 H), 3.35 (s,
3 H), 1.86 (br s, 1 H); 13C NMR (75 MHz, CDCl3) ppm 148.0,
139.6, 128.5, 128.4, 127.6, 127.0, 126.8, 113.7, 85.5, 63.6, 56.9;
MS m/ z (M+) calcd 178.0994, obsd 178.0995.
The conversion of this alcohol to bromide 5d by the
procedure described above was accomplished in 74% yield:
1
colorless oil; IR (CHCl3, cm-1) 1450, 1220, 746; H NMR (300
MHz, CDCl3) δ 5.46 (d, J ) 1.0 Hz, 1 H), 5.20 (s, 1 H), 3.95 (d,
J ) 11 Hz, 1 H), 3.88 (d, J ) 11 Hz, 1 H), 3.39 (d, J ) 7.4 Hz,
1 H), 3.23 (s, 3 H), 2.00-0.80 (series of m, 11 H); 13C NMR (75
MHz, CDCl3) ppm 143.1, 119.0, 88.2, 56.8, 40.9, 31.8, 29.8,
29.4, 26.5, 25.9, 25.8; MS m/ z (M+) calcd 246.0619, obsd
246.0593.
Anal. Calcd for C11H19BrO: C, 53.45; H, 7.75. Found: C,
53.20; H, 7.72.
Gen er a l Allyla tion P r oced u r e. A mixture of the bromide
(1 equiv), indium powder (1 equiv), and aldehyde (1 equiv) in
the solvent of choice (10 mL/mmol of bromide) was stirred
vigorously overnight or until reaction was complete. After
dilution with ethyl acetate, the separated aqueous phase was
extracted with ethyl acetate (3×), and the combined organic
solutions were dried and concentrated. The residue was
Anal. Calcd for C11H14O2: C, 74.12; H, 7.92. Found: C,
73.84; H, 7.79.
A cold (-40 °C) solution of the alcohol (1.58 g, 8.87 mmol)
in CH2Cl2 (22 mL) was treated sequentially with triphen-
ylphosphine (3.49 g, 13.3 mmol) and N-bromosuccinimide (2.11
1
subjected to high-field H NMR analysis and then purified by
flash chromatography on silica gel.

3374 J . Org. Chem., Vol. 62, No. 10, 1997
Paquette et al.
Com p etitive Con su m p tion of 4c a n d 6c. A mixture of
bromides 4c (170 mg, 0.50 mmol) and 6c (113 mg, 0.50 mmol
in water (5 mL) was treated with indium powder (57 mg, 0.50
mmol) and stirred vigorously at rt. Aliquots were removed
after 2 and 6 h and diluted with ethyl acetate. The organic
phase was dried and concentrated, and the residue was
subjected to H NMR analysis at 300 MHz. The 4c/6c ratios
were determined to be 64:36 and 75:25, respectively. Beyond
6 h, the onset of hydrolytic decomposition was noted.
G.D.B. is a GAANN Fellow (1993-1997), and M.B.I. is
an Ohio State University Postdoctoral Fellow (1996-
1997).
Su ppor tin g In for m ation Available: Characterization data
for all coupling products along with copies of the high-
resolution 1H and 13C NMR spectra of those new compounds
for which elemental analyses are not reported (30 pages). This
material is contained in libraries on microfiche, immediately
folllows 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
Ack n ow led gm en t. Funds in support of this re-
search were generously provided by the U.S. Environ-
mental Protection Agency (Grant No. R82-4725-010).
J O970158A