3-Bromopropenyl esters in organic synthesis: Indium- and zinc-mediated entries to alk-1-ene-3,4-diols

Article abstract of DOI:10.1021/jo0262457

Metallic indium and zinc readily add to 3-bromopropenyl acetate (5) and benzoate (6) either in THF or in water, affording the corresponding 3-acyloxyallyl organometallic compounds. Nucleophilic addition to aldehydes opens a route to alk-l-ene-3,4-diols 2 in good to excellent yields. Two synthetic protocols were developed, the former involving indium in THF under Grignard conditions and the latter involving zinc in aqueous ammonium chloride under Barbier conditions. The diastereo-selectivity, under all the conditions examined, mainly depends on the nature of the carbonyl compound; conjugated aldehydes afford syn adducts 2, while unconjugated aldehydes display the opposite anti stereopreference.

Full text of DOI:10.1021/jo0262457

3-Br om op r op en yl Ester s in Or ga n ic Syn th esis: In d iu m - a n d
Zin c-Med ia ted En tr ies to Alk -1-en e-3,4-d iols†
Marco Lombardo,* Stefano Morganti, and Claudio Trombini*
Dipartimento di Chimica “G. Ciamician”, Universita` di Bologna, via Selmi 2, I-40126 Bologna, Italy
trombini@ciam.unibo.it; marlom@ciam.unibo.it
Received J uly 26, 2002
Metallic indium and zinc readily add to 3-bromopropenyl acetate (5) and benzoate (6) either in
THF or in water, affording the corresponding 3-acyloxyallyl organometallic compounds. Nucleophilic
addition to aldehydes opens a route to alk-1-ene-3,4-diols 2 in good to excellent yields. Two synthetic
protocols were developed, the former involving indium in THF under Grignard conditions and the
latter involving zinc in aqueous ammonium chloride under Barbier conditions. The diastereo-
selectivity, under all the conditions examined, mainly depends on the nature of the carbonyl
compound; conjugated aldehydes afford syn adducts 2, while unconjugated aldehydes display the
opposite anti stereopreference.
In tr od u ction
prepared by lithiation at low temperature of a protected
allylic alcohol followed by transmetalation with the
desired metal halide.1,2 Here, we report an alternative,
more practical, and economic route to 4 that involves the
oxidative addition of metallic indium and zinc to the
carbon-halogen bond of a suitable 3-heterosubstituted
allyl bromide, prepared by haloacylation of acrolein.3,4
When acrolein was reacted with acetyl bromide or
benzoyl bromide for 3 days, the 1,2-addition product
initially formed slowly rearranged into the more stable
1,4-addition product 5 (E/ Z ) 80:20) or pure E-6. The
overall process takes place much more efficiently in a few
hours in the presence of a catalytic amount of ZnCl2. By
applying this procedure, we synthesized 3-bromopropenyl
esters 5 and 6 in multigram scale and 50-60% yield after
distillation (5) or crystallization (6) (Scheme 2). Interest-
ingly, the presence of the Lewis acid strongly affects the
CdC bond configuration of 3-bromopropenyl esters 5 and
6, which are obtained as E/ Z ) 35:65 and 50:50 mix-
tures, respectively.
One of the best strategies for the synthesis of densely
functionalized carbon chains involves the addition of
synthetic equivalents of the 1-hydroxyallyl anion (1) to
carbonyl compounds. The R-hydroxyallylation reaction
motif, the alk-1-ene-3,4-diol structure 2, provides a
flexible framework useful for further manipulation; for
example, 2 can be converted into a variety of tetrafunc-
tional target molecules 3, as shown in Scheme 1.
SCHEME 1
In the last two decades, a number of synthetic equiva-
lents of 1, with general structure 4 (Figure 1), have been
developed and the stereochemical outcome of their ad-
dition to carbonyl compounds has been examined, both
in terms of simple diastereoselectivity and of facial
selectivity, when chiral carbonyl compounds were in-
volved.1,2
SCHEME 2
F IGURE 1.
The usefulness of 5, as precursor of indium and zinc
complexes 7 and 8 via oxidative addition (Scheme 3), was
preliminarily attested by us in two approaches to alk-1-
ene-3,4-diols 2, differing on the metal used and on the
protocol adopted.2,5
Resu lts a n d Discu ssion
P r ep a r a tion of 3-Br om op r op en yl Ester s. Hetero-
substituted allylic complexes 4 are almost invariably
P r ep a r a tion of Acetoxya llylin d iu m in THF . De-
spite an extensive interest on indium-mediated organo-
* To whom correspondence should be addressed. Phone: +39 051
2099513. Fax: +39 051 2099456.
† In memory of Professor Angelo G. Giumanini.
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(2) Lombardo, M.; Girotti, R.; Morganti, S.; Trombini, C. Org. Lett.
2001, 3, 2981 and references therein.
(3) Ulich, L. H.; Adams, R. J . Am. Chem. Soc. 1921, 43, 660.
(4) Neuenschwander, M.; Bigler, P.; Christen, K.; Iseli, R.; Kyburz,
R.; Mu¨hle, H. Helv. Chim. Acta 1978, 61, 2047.
10.1021/jo0262457 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/09/2003
J . Org. Chem. 2003, 68, 997-1006
997

Lombardo et al.
SCHEME 3
F IGURE 2.
metallic reactions,6 a single NMR study by Chan ap-
peared in the literature affording evidence about the
formation of discreet allylindium species, when metallic
indium is treated with allyl bromide in water or in aprotic
solvents.7 In analogy to the Chan experiment, we reacted
5 (as a 35:65 E/ Z mixture) with indium in THF-d8 and
followed the reaction by 1H NMR. Despite the complexity
of the spectra, clear information could be traced out. The
initial enolic proton signals of 5 at 7.43 ppm (dt, J ) 1.0/
12.2 Hz, E-5) and 7.19 ppm (dt, J ) 0.8/6.2 Hz, Z-5) begin
to disappear and new signals, due to discreet allylic
indium intermediates (E) γ-7 (at 7.08 ppm, dt, J ) 1.4/
12.0 Hz), (Z) γ-7 (at 6.93 ppm, dt, J ) 1.4/6.2 Hz), and
R-7 (two multiplets at 5.61-5.96 and 5.03-5.50 ppm),
reached a maximum after 0.5 h and then kept almost
constant for the following 20 h. The two multiplets due
to R-7 contain contributions of vinylic hydrogens of Wurtz
dimerization products, and of H-2 of (E) and (Z) γ-7. Since
the amount of dimerization products was determined to
range from 5 to 10% in a series of independent reactions,
we could deduce from integral ratios, after subtraction
of the known contributions, the following composition:
R-7/(Z) γ-7/(E) γ-7 ≈ 50:40:10 (Scheme 4).
about R-7, since vinylic protons of adduct 9 (Figure 2)
resonate at the same frequencies of vinylic protons of R-7.
This last experiment told us that (Z) γ-7 is slightly
more reactive than (E) γ-7, and that the kinetic rate
constants relative to the addition of (E) γ-7 and (Z) γ-7
to the aldehyde are higher than the (E) γ-7 S (Z) γ-7
interconversion. Since it is plausible to assume that
reactions of 7 with aldehydes occur with allylic inversion
via cyclic transition states, we may conclude that R-7 has
no tendency to add to the carbonyl group, since traces of
the expected enolacetates 10 (Figure 2) were never
detected.
Wurtz-type dimers of 5 were found to be present in
5-10% yield after 4 h at 25 °C, as demonstrated after
isolation of hexa-1,5-diene-3,4-diol, upon overnight hy-
drolysis of the reaction mixture with K2CO3 in MeOH/
H2O.
Th e Rea ction of Acyloxya llylin d iu m Rea gen ts
w ith Ald eh yd es (Gr ign a r d P r otocol). At the outset
of this research, our goal was to exploit zinc in a
Grignard-type reaction of 5 (as a 35:65 E/ Z isomer
mixture) with aldehydes in THF. When zinc and 5 were
stirred for 12 h at 10 °C in THF and cyclohexanecarbox-
aldehyde was added, 9 (R ) cyclohexyl) was isolated in
40% yield as a 12:88 syn/anti mixture. Quite disappointed
by these results, we decided to move to the more
expensive but also more reactive indium. Indium im-
mediately revealed much more promising and allowed
us to develop a simple synthetic procedure for the
synthesis of alk-1-ene-3,4-diols 2.
SCHEME 4
In a first set of reactions (Table 1), unless otherwise
stated, we preformed the organometallic species in
anhydrous THF, by stirring indium powder and 5 or 6
in the 1:1.5 molar ratio, and then an aldehyde (1 equiv)
was added.
We are not in the position to assign the observed
intermediates to InI or InIII species, however, according
to Chan results,7 intermediates 7 are expected to cor-
respond to InIII species, since InI signals should have been
greatly reduced or completely disappeared after 20 h.
Since the same R-7/(Z) γ-7/(E) γ-7 ratio was observed
after 3 h using an E enriched mixture of 5 (E/ Z ) 80:
20), the observed composition of allyl indium species is
supposed to be the result of a thermodynamic equilibra-
tion.
In a further experiment, cyclohexanecarboxaldehyde
(0.2 equiv) was added to a solution of 7 in THF-d8
obtained by reacting indium with 5 for 2 h at 25 °C; after
5 min, both (E) γ-7 and (Z) γ-7 peak intensities decreased
with respect to internal TMS and reached the 30:70
relative ratio; then, a further 0.4 equiv of cyclohexan-
ecarboxaldehyde was added and (E) γ-7 and (Z) γ-7
intensities decreased to very low levels and reached a
∼1:1 ratio. The 1H NMR did not give any information
TABLE 1. In d iu m -Med ia ted Gr ign a r d Rou te to
Alk -1-en e-3,4-d iols 2a
substrate
(E/Z)
t1
(h) (°C)
T2 2 yieldb syn/
entry
R-CHO
(%)
anti
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
5 (35:65) Ph
5 (35:65) Ph
4
4
4
0
0
4
4
4
0
0
4
4
4
4
4
0
-78
86
91
77
80
94
90
70
65
70
88
83
95
96
79
72
75:25
85:15
75:25
70:30
70:30
15:85
10:90
15:85
10:90
10:90
35:65
30:70
70:30
85:15
90:10
6 (99:1)
Ph
0
0
0
0
5 (35:65) Ph
5 (75:25) Ph
5 (35:65) cyclohexyl
5 (35:65) cyclohexyl
6 (50:50) cyclohexyl
-78
0
0
0
0
0
5 (35:65) cyclohexyl
5 (75:25) cyclohexyl
5 (35:65) (CH3)2CH-CH2-
5 (35:65) Ph-CH2-CH2-
5 (35:65) (E)-Ph-CHdCH-
5 (35:65) CH2)(CH3)CH-
5 (35:65) 2-furyl
0
0
(5) Lombardo, M.; Girotti, R.; Morganti, S.; Trombini, C. Chem.
Commun. 2001, 2310.
(6) (a) Cintas, P. Synlett 1995, 1087. (b) Li, C. J .; Chan, T. H.
Organic Reactions in Aqueous Media; Wiley: New York, 1997. (c)
Paquette, L. A. In Green Chemistry: Frontiers in Benign Chemical
Synthesis and Processing; Anastas, P., Williamson, T., Eds.; Oxford
University Press: New York, 1998.
-78
a
The following molar ratio was used: indium/5/aldehyde )
b
1:1.5:1. Isolated yields of deprotected diols 2 after overnight
treatment of the reaction mixture with K2CO3 (3 equiv) in MeOH/
H2O 9:1.
(7) Chan, T. H.; Yang, Y. J . Am. Chem. Soc. 1999, 121, 3228.
998 J . Org. Chem., Vol. 68, No. 3, 2003

3-Bromopropenyl Esters in Organic Synthesis
TABLE 2. Op tim iza tion Stu d ies of th e In d iu m -Med ia ted Rou te to Alk -1-en e-3,4-d iols 2a
entry
R-CHO
T1(°C)/t1(min) cosolvent in step 2
T2 (°C)/ t2 (min) 2 (syn/anti) 9 (syn/anti) 12 (syn/anti) 15 (syn/anti)
1
2
3
4
5
6
c-C6H11
C6H5
c-C6H11
c-C6H11
c-C6H11
C6H5
0 f 25/240
0 f 25/240
0 f 25/45
0 f 25/45
0 f 25/45
0 f 25/45
none
none
0/240
0/240
25/45
25/45
25/45
25/45
18 (1:99)
33 (45:55)
22 (1:99)
0
0
0
20 (10:90)
13 (95:5)
10 (5:95)
30 (10:90)
50 (10:90)
50 (65:35)
25 (4:96)
33 (85:15)
30 (5:95)
0
0
0
25 (40:60)
13 (99:1)
27 (40:60)
65 (15:85)
45 (20:80)
42 (80:20)
none
H2Ob
H2O (pH 3)c
H2O (pH 3)c
a
All the reactions were carried out on 1 mmol of aldehyde in 2 mL of THF, adopting the same molar ratios reported in Table 1.
Water (0.2 mL) was added immediately before the addition of the aldehyde. c A pH 3 aq solution (phthalate buffer, 0.2 mL) was added
b
immediately before the addition of the aldehyde.
The experimental conditions were fixed as follows:
step 1 (formation of the organometallic species): reac-
tion time (t1) ) 4 h, reaction temperature (T1) was set at
0 °C for 15 min and then allowed to raise to 25 °C;
step 2 (nucleophilic addition): reaction time (t2) ) 4
h, reaction temperature (T2) ) 0 °C.
A main drawback associated with this procedure is the
occurrence of intra- and intermolecular acyl transfer
reactions due to nucleophilicity of the intermediate
indium alkoxide groups. The overall picture of trans-
esterification reactions occurring downstream the forma-
tion of adduct 11 is reported in Scheme 5.
complexes 4, whose diastereoselectivity is independent
of the aldehyde used.
Barbier conditions (t1 ) 0) were also tested (entries 4,
5, 9, and 10), which afforded comparable results in terms
of chemical yields but with a slightly lower diastereopref-
erence when benzaldehyde was used.
Furthermore, to check a possible role played by the
acyloxy substituent on the stereochemical outcome of the
reaction, we carried out two reactions with 6: the results
(Table 1, entries 3 and 8), despite a different distribution
of intermediate indium species, revealed an impressive
identity in terms of stereochemical results with those
obtained with 5 (entries 1 and 6).
Op t im iza t ion St u d ies. As previously outlined, the
crude reaction mixture contained a group of four products
2, 12, 9, and 15 (Scheme 5). Table 2 collects a few
experiments aimed at (i) evaluating the relative amount
of each product and their syn/anti composition, (ii)
limiting the occurrence of side reactions, and (iii) opti-
mizing reaction conditions in terms of reaction time and
temperature.
SCHEME 5
Entries 1 and 2 report the product distribution of two
model reactions carried out according our previous
protocol (Table 1, entries 1 and 6), confirming a high
degree of side-transesterification processes. When t1 was
lowered to 45 min and addition to the aldehyde was
carried out at T2 ) 25 °C (entry 3), conversion, product
distribution, and stereocomposition were almost identical
to those obtained in entry 1. What is deduced from entries
1-3 is that syn adducts selectively give the intramolecu-
lar acyl transfer reaction leading to 15, as expected by
the less congestion of the quasi-eclipsed conformation
required for the acyl transfer reaction. On the other hand,
anti adducts preferentially undergo intermolecular acyl
transfer reactions, leading to 2 and 12.
The subsequent series of experiments (entries 4-6)
were designed in order to exploit kinetic advantages
offered by water as cosolvent in the carbonyl addition
step, both under neutral and acidic pH, as previously
reported by Paquette.8 Besides to affect yield and dia-
stereoselectivity, the hope was to suppress the acetyl
scrambling reactions by protonating the intermediate
indium alkoxides. Toward this purpose, the organoin-
dium species were preformed, as usual, in anhydrous
THF for 45 min, then water (entry 4) or a pH 3 buffered
solution (entries 5,6) was added, followed by the addition
of the carbonyl compound. Since entry 3 told us that the
original reaction times t1 and t2 were overestimated and
that there was no advantage to carry out the organome-
tallic addition to the aldehyde at 0 °C (entry 3), we set t1
To overcome the complexity of the reaction mixture
associated to transesterification processes, we directly
hydrolyzed the crude reaction mixture containing esters
9, 12, and 15 to 1-ene-3,4-diols 2 (K2CO3, 3 equiv,
methanol/water 9:1). The final syn/anti ratio of deacylated
2 reflects the original stereopreference of the addition of
7 to the aldehyde, since transesterification reactions do
not affect the stereogenic centers formed in the carbonyl
addition step.
The most relevant results obtained with indium under
Grignard conditions are collected in Table 1.
Isolated chemical yields varied in the range 70-96%
yield, and simple diastereoselectivities were found to be
dependent on the nature of the aldehyde. In particular,
conjugated aldehydes (entries 1-5, 13-15) exhibited syn
selectivity (syn/anti ) 60/40-90/10), while saturated
aldehydes (entries 6-12) clearly showed the inverse anti
stereopreference (syn/anti ) 35/65-10/90). Such behavior
is not common to other heterofunctionalized allylic metal
(8) Paquette, L. A.; Mitzel, T. M. J . Am. Chem. Soc. 1996, 118, 1931.
J . Org. Chem, Vol. 68, No. 3, 2003 999

Lombardo et al.
and t2 at 45 min and T2 at 25 °C. Under these new
conditions, intermolecular processes were completely
suppressed, but the same did not happen for the in-
tramolecular transesterification, which still was a major
side reaction.
Independently of the presence of rearranged adducts
15, reactions carried out under these new conditions seem
to be highly attractive under an overall efficiency point
of view, both as refers to chemical yields and to stereo-
selectivity which seems to increase in absolute terms.
As a further attempt to improve the economy of the
reaction, we tested a catalytic version of our protocol in
order to reduce the amount of the expensive indium
metal, based on the known redox couple formed by
indium(III) and cheap commercial manganese powder.9
Indium powder (0.1 equiv) was added to a stirred mixture
of manganese powder (2 equiv), 5 (1.5 equiv), TMSCl (1.1
equiv), and benzaldehyde (1 equiv); adopting the same
experimental conditions of Table 1, entry 4 we got the
product 2 (R ) Ph) in a slightly lower yield (60%) and
poorer diastereoselectivity (syn/anti ) 65:35).
Th e In d iu m Rou te to Alk -1-en e-3,4-d iols: Sim p le
Dia ster eoselectivity. Since it is known that the allyl-
metalation of aldehydes,10 as well as of imines,11 is a
reversible process, we checked the de values after dif-
ferent time intervals in two reactions, using benzalde-
hyde and cyclohexancarboxaldehyde, respectively, to
ascertain whether the different diastereoselectivities
observed with conjugated and unconjugated aldehydes
are the result of thermodynamic equilibration. Quenching
experiments at different reaction times (5, 10, 30, 60, 120,
and 1200 min) following the experimental procedure
reported in Table 1 (entries 1 and 6) unambiguously show
that there was no change in diastereomeric excess in both
cases.
F IGURE 3.
Considering that (Z) γ-7, the major reactive allylindium
species present in solution, is expected to be the major
responsible for the final stereochemical outcome, we
suggest that twist-boat transition states (TS), stabilized
with respect to chairlike TS by intramolecular chelation,
are preferentially adopted. In Figure 3, structures A and
B represent the two possible twisted conformations of
hypothetical bicyclo[3.2.2]nonane-type TS, deriving from
the approach of benzaldehyde si face to the si face of (Z)-
7, while C and D refer to the alternative approach of
benzaldehyde re face to the si face of (Z)-7.
We believe that a delicate balance of steric, stereoelec-
tronic and dipolar effects are at the basis of stereocross-
over in the reaction of (Z) γ-7 with aldehydes. On purely
steric grounds, the less hindered location for the aldehyde
substituent seems to be found in TS-C, thus implying
that formation of anti-9 should be favored. On the other
hand, if the aldehyde is conjugated, TS-A offers the
unsaturated group, e.g., the phenyl ring, the opportunity
of meeting face to face the acetoxy carbonyl group, thus
developing an attractive stabilizing interaction. In our
opinion, π-staking12 can account for the syn stereopref-
erence of conjugated aldehydes.
These issues await detailed analysis, but whatever the
explanation a clear dependence of the reaction outcome
on the nature of the aldehyde has been demonstrated.
P r ep a r a tion a n d Rea ctivity of Acetoxya llylin -
d iu m a n d Zin c Sp ecies in Wa ter . Within the frame-
work of green chemistry principles,13 one of the priority
research areas deals with design and utilization of
alternative solvents, with reduced environmental impact.
Significant attention has been devoted in the past decade
to replace volatile, dangerous and toxic solvents with
water; a major breakthrough is represented by the
reaction of indium and zinc allyl complexes with carbonyl
compounds in water,6 which is denoted by high levels of
A further experiment to check possible thermodynamic
control was designed as follows: two mixtures of
monoacetylated products 9 and 15, deriving from pure
syn-2 (R ) Ph) and from an anti-enriched mixture of 2
(syn/anti ) 35:65, R ) Ph), respectively, were added to a
solution of allyliindium derivatives 7, prepared in THF
as previously reported. After stirring at 25 °C for 40 min,
quenching, and overnight deacetylation, diol 2 revealed
1
by H NMR analysis exactly the same original stereo-
chemical composition. The absence of epimerization
under typical reaction conditions confirms that thermo-
dynamic equilibration does not play any role on the final
stereochemical outcome.
Thus, the stereochemical outcome of the acetoxyally-
lation of aldehydes in THF using indium should be
controlled by kinetic reasons. On this basis, if both (E)
γ-7 and (Z) γ-7 adopted chairlike transition states (TS),
according to the classical Zimmermann-Traxler theory,
syn-9 should always prevail, (Z) γ-7 being both the more
abundant and the more reactive indium intermediate
present in solution.
(12) As examples of asymmetric induction promoted by π-staking
between an ester group and an aromatic ring, see the chemistry of (a)
8-arylmenthol-derived chiral auxiliaries (J ones, G. B.; Chapman, B.
J . Synthesis, 1995, 475) and of (b) Diels-Alder catalysts based on
6-naphthylcyclohexyldichloroborane: Hawkins, J . M.; Loren, S.; Nam-
bu, M. J . Am. Chem. Soc. 1994, 116, 1657.
(13) Tundo, P.; Anastas, P.; Black, D. StC.; Breen, J .; Collins, T.;
Memoli, S.; Miyamoto, J .; Polyakoff, M.; Tumas, W. Pure Appl. Chem.
2000, 72, 1207.
(9) Auge´, J .; Lubin-Germain, N.; Thiaw-Woaye, A. Tetrahedron Lett.
1999, 40, 9245. See also Steurer, S.; Podlech, J . Adv. Synth. Catal.
2001, 343, 251.
(10) (a) J ones, P.; Knochel, P. J . Org. Chem. 1999, 64, 186. (b)
Barbot, F.; Miginiac, P. J . Organomet. Chem. 1977, 132, 445, and ref.
therein.
(11) Grilli, S.; Martelli, G.; Savoia, D. Eur. J . Org. Chem. 2001, 2917
and references therein.
1000 J . Org. Chem., Vol. 68, No. 3, 2003

3-Bromopropenyl Esters in Organic Synthesis
TABLE 3. Syn th esis of Mon oa cetyla ted Alk -1-en e-3,4-d iol Der iva tives 9 a n d 15 in Wa ter u n d er Ba r bier Con d ition sa
entry
substrate
R-CHO
metal
solventb
Tc (°C)
9 + 15 overall yieldd (%)
syn/antie
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
5
5
5
5
5
5
Ph
Ph
In
In
In
H2O
22f
22f
22f
22
22
4
25
25
2
24
22
24
24
20
22
22
25
22
22
22
75
79
84
65
90
80
80
86
81
60
0
70:30
70:30
20:80
65:35
65:35
70:30
55:45
50:50
80:20
60:40
-
H2O/THFg
H2O/THFg
H2O
cyclohexyl
Ph
Ph
Ph
Ph
Ph
2-furyl
4-tolyl
4-nitrophenyl
4-fluorophenyl
4-anisyl
(E)-PhCHdCH
cyclohexyl
cyclohexyl
cyclohexyl
n-C6H13
PhCH2CH2
(CH3)2CHCH2
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
NH4Cl/H2O
6h
6i
5
5
5
5
5
0
-
72
81
84
80
80
84
81
76
70:30
60:40
30:70
15:85
15:85
30:70
30:70
30:70
5
5
6h
6i
5
5
5
a
Starting 5 was always used as a 35:65 E/Z mixture. b Unless otherwise stated, saturated aqueous ammonium chloride is used. c External
d
bath temperature ((1 °C). Isolated yields. The 9/15 ratio ranged from 80:20 to 70:30 when conjugated aldehydes were used and 95:5 to
90:10 in the other cases. e Determined on the corresponding alk-1-ene-3,4-diols after hydrolysis of the crude reaction mixture with K2CO3.
f The reaction mixture was stirred for 6 h. A 1:1 v/v mixture was used. Pure (E)-6 was used. A 1:1 E/ Z mixture of 6 was used.
g
h
i
regio- and diastereoselectivity.14 We decided to explore
the reaction of 5 and 6 with indium in water, in the
presence of an aldehyde under typical Barbier conditions,
even though indium works at acidic pH15 and the enol-
ester functionality of 5 and 6 is sensitive to hydrolysis
under these conditions.
Even though these preliminary results were encourag-
ing, economy criteria impelled us to check zinc also, a
much less expensive metal, whose chemical reactivity
toward allyl halides parallels that of indium. We were
delighted by the observation that zinc was even superior
to indium in terms of reaction rates and conversions,
particularly in saturated ammonium chloride as the
reaction medium. Pure water could be used as solvent
but results were inferior, as shown by entries 4 and 5.
We first followed by 1H NMR the reaction of an
equimolar amount of 5 and metallic indium in D2O. After
5 min, two weak doublets were detected at 6.55 ppm (1H,
J ) 6.0 Hz) and at 1.57 ppm (2H, J ) 9.6), assignable to
a discreet (Z) γ-7 allylindium species. Since these peaks
disappeared within 10 min, they should be assigned to
an indium(I) complex according to Chan observation of
simple allylindium(I) in D2O.7 Addition of cyclohexane-
carboxaldehyde after 5 min afforded a mixture of Wurtz
products in 50% yield and adducts 9 + 15 (R ) cyclo-
hexyl) in 30% overall yield.
Due to the very fast Wurtz dimerization in water, the
only chance was to rely on a Barbier protocol; starting
bromide 5 or 6 was added to the stirred mixture of the
aldehyde and indium powder in water.16 Very luckily, the
interaction of 5 or 6 with the metal was even more rapid
than Wurtz dimerization, and good to excellent amounts
of adducts 9 and 15 could be isolated after short reaction
times. Results of a series of experiments carried out
according to this new protocol are collected in Table 3
(entries 1-3). Conversions were good, and interestingly
the same stereochemical trend observed in THF under
Grignard conditions was confirmed in water under Bar-
bier conditions: benzaldehyde favors the formation of a
syn-enriched adduct 9, and cyclohexanecarboxaldehyde
favors the anti adduct 9.
A number of experiments are collected in Table 3
(entries 5-20) where conjugated and unconjugated al-
dehydes are used. Again, the general stereochemical
trend is preserved even though using 5, the diastereo-
selectivity is lower both with respect to the use of indium
in water (cfr. entries 1, 2, 4, 5 and 3, 15) and in THF
(Table 1). Replacement of the acetoxy for the benzoyloxy
group had opposite effects when benzaldehyde or cyclo-
hexanecarboxaldehyde were used: diastereoselectivity
was almost completely lost with benzaldehyde (entries 7
and 8), while the latter aldehyde afforded the best excess
of anti adduct 2 (entries 16 and 17). These experiments
also confirm that the final stereochemical results are
independent of the geometry of the starting bromide.
Thus, an exceptionally mild and simple Barbier pro-
tocol (zinc and ammonium chloride) was developed using
5 or 6, allowing to isolate monoacetylated products 9
accompanied by lower amount of 15 (5-30%), in very
good overall yields. Intramolecular transesterification
mainly involves syn-9, which better accommodates sub-
stituents to the C3-C4 bond in the quasi-eclipsed
conformation required by the acyl transfer reaction. This
also accounts for why compounds 15 are present to a
major extent (20-30%) when conjugated aldehydes are
used.
(14) (a) Isaac, M. B.; Chan, T. H. Tetrahedron Lett. 1995, 36, 8957.
(b) Isaac, M. B.; Chan, T. H. J . Chem. Soc., Chem.. Commun. 1995,
1003. (c) Paquette, L. A.; Mitzel, T. M. J . Org. Chem. 1996, 61, 8799.
(d) Paquette, L. A.; Lobben, P. C. J . Org. Chem. 1998, 63, 5604.
(15) Indium salts formed during the reaction undergo acidic hy-
drolysis which lowers the pH up to 3.
(16) We found that it was sufficient to add 5 and 6 to the stirred
mixture of the metal in water to avoid any hydrolysis of the starting
material.
Among aromatic aldehydes, 4-nitro and 4-fluorobenz-
aldehyde did not afford any adduct, a sticky insoluble
material being formed in both cases; no further investi-
gation was done in order to ascertain the fate of these
aldehydes in our reaction system.
J . Org. Chem, Vol. 68, No. 3, 2003 1001

Lombardo et al.
SCHEME 6
astereoselectivity mainly depends on the nature of the
carbonyl compound, rather than on the geometry of the
double bond of the allylic organometal.
Exp er im en ta l Section
1
Gen er a l Meth od s. H and 13C NMR were recorded at 300
and 75 MHz, respectively, using tetramethylsilane as an
internal standard. Melting points are uncorrected. All reagents
were commercially available and were used without further
purification, unless otherwise stated.
3-Br om op r op en yl Aceta te (5). P r oced u r e A. Flame-
dried ZnCl2 (0.068 g, 0.5 mmol) was added at -20 °C to a
mixture of freshly distilled acrolein (3.32 mL, 50 mmol) and
acetyl bromide (3.73 mL, 50 mmol) in anhydrous CH2Cl2 (40
mL). The reaction was stirred for 2 h at 0 °C and quenched at
0 °C by addition of aqueous NaHCO3. The aqueous layer was
extracted with CH2Cl2, the combined organic phases were dried
(Na2SO4), and CH2Cl2 was removed by distillation at atmo-
spheric pressure. Further purification of the residue by distil-
lation (bp ) 69-71 °C, P ) 22 Torr) afforded 5.44 g (30.5 mmol,
61%) of 5 as a 35:65 mixture of E/Z isomers. P r oced u r e B.
Acetyl bromide (1.49 mL, 20 mmol) was added at 0 °C to
freshly distilled acrolein (1.33 mL, 20 mmol) in anhydrous CH2-
Cl2 (20 mL). The ice bath was removed, and the reaction was
stirred for 72 h at rt. The reaction was quenched at 0 °C by
addition of aqueous NaHCO3, the aqueous layer was extracted
with CH2Cl2, the combined organic phases were dried (Na2-
SO4), and CH2Cl2 was removed by distillation at atmospheric
pressure. Further purification of the residue by distillation (bp
) 69-71 °C, P ) 22 Torr) afforded 2.51 g (14 mmol, 70%) of 5
as a 75:25 mixture of E/ Z isomers. (Z)-5: 1H NMR (300 MHz,
CDCl3) δ 2.22 (s, 3H), 4.09 (dd, J ) 0.3/8.1 Hz, 2H), 5.24 (dt,
J ) 6.3/8.1 Hz, 1H), 7.19 (dt, J ) 0.3/6.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 20.5, 23.5, 109.3, 136.9, 166.9. (E)-5: 1H
NMR (300 MHz, CDCl3) δ 2.16 (s, 3H), 3.99 (dd, J ) 0.3/8.1
Hz, 2H), 5.70 (dt, J ) 8.1/12.3 Hz, 1H), 7.19 (dt, J ) 0.3/12.3
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 20.5, 28.4, 111.1, 139.0,
167.2. Anal. Calcd for C5H7BrO2: C, 33.55; H, 3.94; Br, 44.64.
Found: C, 33.48; H, 4.01; Br, 44.72.
Assign m en t of Syn /An ti Ster eoch em istr y to Ad -
d u ct s 2. As a general strategy to assign relative syn/
anti stereochemistry to adducts 2, we converted them into
acetonides 16 and studied NOEs in both stereoisomers
(Scheme 6).
While performing these transformations, a few regu-
larities came out, which may be useful to chemists
working on this field.
(i) We confirmed a previous observation by J iang et
al.17 on alk-1-ene-3,4-diols 2. Invariably, the chemical
shift of the homoallylic proton (H-4) in syn-2 resonates
at 0.1-0.3 ppm upfield from that of anti-2.
(ii) The chemical shift difference of the methyl groups
in position 2 is always greater in cis-16 (0.12-0.14 ppm)
than in trans-16 (0.01-0.04 ppm).
(iii) GC retention times of trans-16 are always shorter
than those of cis-16 (HP-5 cross linked 5% Me Ph
silicone).
3-Br om op r op en yl Ben zoa te (6). P r oced u r e A. Using the
same procedure described for 5, 3-bromopropenyl benzoate 6
was obtained in 54% yield as a 45:55 mixture of E/ Z isomers
after purification by flash chromatography on silica (cyclohex-
ane/ethyl acetate ) 90/10). P r oced u r e B. Using the same
procedure B described for 5, 3-bromopropenyl benzoate 6 was
obtained in 77% yield as pure E isomers after recrystallization
from pentane. (Z)-6: 1H NMR (200 MHz, CDCl3) δ 2.22 (s, 3H),
4.09 (dd, J ) 0.3/8.1 Hz, 2H), 5.24 (dt, J ) 6.3/8.1 Hz, 1H),
7.19 (dt, J ) 0.3/6.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
23.5, 110.0, 128.6, 130.0, 133.9, 137.5, 160.2, 162.6. (E)-6: mp
) 74-76 °C (pentane); 1H NMR (300 MHz, CDCl3) δ 4.08 (dd,
J ) 0.9/8.4 Hz, 2H), 5.91 (dt, J ) 8.4/12.3 Hz, 1H), 7.46-7.53
(m, 2H), 7.60-7.66 (m, 1H), 7.69 (dt, J ) 1.1/12.3 Hz, 1H),
8.08-8.13 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 28.5, 111.8,
128.5, 130.0, 133.8, 139.4, 160.2, 163.1. Anal. Calcd for C10H9-
BrO2: C, 49.82; H, 3.76; Br, 33.14. Found: C, 49.89; H, 3.71;
Br, 33.10.
Hyd r oxya llyla tion Rea ction s Usin g In d iu m in THF .
Typ ica l P r oced u r e (A). 3-Bromopropenyl acetate 5 (0.175
mL, 1.5 mmol) was added at 0 °C to a suspension of indium
powder (0.115 g, 1 mmol) in THF (2 mL). The heterogeneous
mixture was stirred for 30 min at 0 °C, the ice bath was
removed, and stirring was continued for 3.5 h at rt. Benzal-
dehyde (0.105 mL, 1 mmol) was added at 0 °C, and the reaction
mixture was stirred for 4 h at 0 °C. Water was added (0.5 mL),
and the reaction mixture was stirred for 5 min and filtered
(Celite). The aqueous layer was extracted with ether, and the
combined organic layers were dried (Na2SO4) and evaporated
at reduce pressure. Purification by flash chromatography on
SiO2 (cyclohexane/ethyl acetate 9:1) afforded 0.082 g of 12a
(0.33 mmol, 33%, anti/syn ) 15:85), 0.054 g of a 1/1 mixture
of 9a (0.13 mmol, 13%, anti/syn ) 5:95) and 15a (0.13 mmol,
Con clu sion s
The usefulness of 3-bromopropenyl esters 5 and 6 as
formal precursors of the R-hydroxyallyl anion 1 has been
demonstrated. In summary:
(i) 3-bromopropenyl esters are prepared in multigram
scale and in good yield by simply mixing acrolein and
acetyl bromide or benzoyl bromide; when ZnCl2 was
present, the reaction rate remarkably increased and
stereoselectivity changed, favoring the formation of the
Z isomers.
(ii) 3-Bromopropenyl esters easily undergo oxidative
addition by zinc and indium in a variety of reaction
conditions. The tolerability of a wide range of experi-
mental parameters (solvents, temperature, experimental
procedures, etc.) is useful in terms of optimization
purposes, for example, when substrates other than al-
dehydes are examined. A very recent example was
reported by Petrini et al.,18 who opened a new route to
anti-4-aminoalk-1-en-3-ols using R-amidoalkylphenyl sul-
fones as electrophiles. The best conditions involved the
use of zinc and 5 in THF for 24 h at room temperature.
(iii) The use of ester functionality as the Z group in
the heterosubstituted allylic species 4 determined an
unprecedented stereochemical consequence: simple di-
(17) J iang, S.; Agoston, G. E.; Chen, T.; Cabal, M. P.; Turos, E.
Organometallics 1995, 14, 4697.
(18) Petrini, M.; Profeta, R.; Righi, P. J . Org. Chem. 2002, 67, 4530.
1002 J . Org. Chem., Vol. 68, No. 3, 2003

3-Bromopropenyl Esters in Organic Synthesis
13%, anti/syn ) 1:99), and 0.054 g of 2a (0.33 mmol, 33%, anti/
syn ) 55:45).
By applying the same experimental procedure to cyclohex-
anecarboxaldehyde (0.120 mL, 1 mmol), 0.106 g of 9b (0.5
mmol, 50%, anti/syn ) 90:10) and 0.096 g of 15b (0.45 mmol,
45%, anti/syn ) 80:20) were obtained after purification by flash
chromatography on SiO2 (cyclohexane/ethyl acetate 9:1).
Syn th esis of 1-P h en ylbu t-3-en e-1,2-d iol (2a ). Typ ica l
P r oced u r e. The crude reaction mixture obtained by procedure
A or B was dissolved in MeOH/H2O (5 mL, 9:1 v/v), K2CO3
(0.415 g, 3 mmol) was added, and the reaction mixture was
stirred at rt overnight. MeOH was removed at reduced
pressure, and the aqueous layer was extracted with ether. The
combined organic layers were dried (Na2SO4) and evaporated
at reduce pressure. Purification by flash chromatography on
SiO2 (cyclohexane/ethyl acetate 8:2) afforded 0.105 g of syn-
2a (0.64 mmol, 64%) and 0.035 g of anti-2a (0.21 mmol, 21%).
syn -1-P h en ylbu t-3-en e-1,2-d iol (syn -2a ): 1H NMR (300
MHz, CDCl3) δ 2.42 (d, J ) 1.8 Hz, 1H), 2.78 (d, J ) 1.2 Hz,
1H), 4.19-4.30 (m, 1H), 4.52 (dd, J ) 1.8/6.9 Hz, 1H), 5.17
(dt, J ) 1.5/10.5 Hz, 1H), 5.28 (dt, J ) 1.5/16.8 Hz, 1H), 5.75
(ddd, J ) 5.1/10.5/16.8 Hz, 1H), 7.28-7.42 (m, 5H); 13C NMR
(75 MHz, CDCl3) δ 76.8, 77.5, 116.8, 127.0, 127.9, 128.2, 136.1,
140.1. Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C,
73.21; H, 7.38.
a n ti-1-P h en yl-bu t-3-en e-1,2-d iol (a n ti-2a ): 1H NMR (300
MHz, CDCl3) δ 2.02 (d, J ) 3.9 Hz, 1H), 2.40 (d, J ) 2.0 Hz,
1H), 4.30-4.39 (m, 1H), 4.78 (t, J ) 3.9 Hz, 1H), 5.24 (dt, J )
1.4/10.5 Hz, 1H), 5.30 (dt, J ) 1.4/17.5 Hz, 1H), 5.75 (ddd, J )
6.3/10.5/17.5 Hz, 1H), 7.27-7.40 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 76.3, 76.5, 117.5, 126.5, 127.6, 128.1, 135.4, 139.7.
Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.19;
H, 7.69.
syn -1-Cycloh exylbu t-3-en e-1,2-d iol (syn -2b): 1H NMR
(300 MHz, CDCl3) δ 0.95-1.48 (m, 5H), 1.56-1.88 (m, 4H),
1.89-2.18 (m, 2H), 3.21-3.28 (m, 1H), 4.15-4.21 (m, 1H), 5.26
(dt, J ) 1.3/10.5 Hz, 1H), 5.37 (dt, J ) 1.3/17.5 Hz, 1H), 5.90
(ddd, J ) 6.3/10.5/17.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
26.0, 26.2, 26.3, 27.1, 29.6, 29.9, 39.4, 73.0, 78.3. Anal. Calcd
for C10H18O2: C, 70.55; H, 10.66. Found: C, 70.61; H, 10.72.
a n ti-1-Cycloh exylbu t-3-en e-1,2-d iol (a n ti-2b): 1H NMR
(300 MHz, CDCl3) δ 0.93-1.48 (m, 5H), 1.58-1.86 (m, 4H),
1.88-2.20 (m, 2H), 3.39-3.48 (m, 1H), 4.20-4.29 (m, 1H), 5.31
(dt, J ) 1.4/10.5 Hz, 1H), 5.38 (dt, J ) 1.4/17.5 Hz, 1H), 5.99
(ddd, J ) 6.6/10.5/17.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
25.7, 25.8, 26.3, 28.7, 29.0, 39.7, 73.3, 78.0. Anal. Calcd for
syn -3,4-Diacetoxy-4-ph en ylbu t-1-en e (syn -12a): 1H NMR
(200 MHz, CDCl3) δ 2.00 (s, 3H), 2.02 (s, 3H), 5.07-5.14 (m,
1H), 5.18-5.23 (m, 1H), 5.43-5.64 (m, 2H), 5.79 (d, J ) 5.6
Hz, 1H), 7.29-7.40 (m, 5H). The following signal in the
previous NMR spectra is assigned to the anti isomer: 1H NMR
δ 5.90 (d, J ) 4.7 Hz, 1H).
syn -4-P h en yl-4-a cetoxybu t-1-en -3-ol (syn -15a ): 1H NMR
(300 MHz, CDCl3) δ 2.14 (s, 3H), 4.45 (ddt, J ) 1.6/5.4/6.8 Hz,
1H), 5.19-5.28 (m, 2H), 5.69 (d, J ) 6.8 Hz, 1H), 5.63-5.73
(m, 1H), 5.29-5.40 (m, 5H).
a n ti-1-P h en yl-2-a cetoxybu t-3-en -1-ol (a n ti-9a ): 1H NMR
(200 MHz, CDCl3) δ 2.08 (s, 3H), 4.90 (d, J ) 4.4 Hz, 1H),
5.28 (dt, J ) 1.5/17.0 Hz, 1H), 5.29 (dt, J ) 1.3/10.8 Hz, 1H),
5.48 (ddt, J ) 1.2/4.4/6.8 Hz, 1H), 5.82 (ddd, J ) 6.8/10.8/17.0
Hz, 1H), 7.28-7.43 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 21.0,
75.1, 78.1, 119.6, 126.6, 128.0, 128.3, 131.6, 139.5, 170.0. Anal.
Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.95; H,
6.79.
1
syn -1-P h en yl-2-a cetoxybu t-3-en -1-ol (syn -9a ): H NMR
(300 MHz, CDCl3) δ 2.12 (s, 3H), 4.76 (d, J ) 6.5 Hz, 1H),
5.13-5.36 (m, 2H), 5.42-5.52 (m, 1H), 5.60-5.75 (m, 1H),
7.30-7.41 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 21.1, 75.0,
78.0, 119.5, 126.5, 127.9, 128.3, 131.5, 139.3, 169.9. Anal. Calcd
for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.97; H, 6.85.
By applying the same experimental procedure to cyclohex-
anecarboxaldehyde (0.120 mL, 1 mmol), purification by flash-
chromatography on SiO2 (cyclohexane/ethyl acetate 9:1) af-
forded 0.064 g of 12b (0.25 mmol, 25%, anti/syn ) 96:4), 0.042
g of 9b (0.20 mmol, 20%, anti/syn ) 90:10), 0.053 g of 15b (0.25
mmol, 25%, anti/syn ) 60:40), and 0.031 g of 2b (0.18 mmol,
18%, anti/syn ) 99:1).
a n ti-3,4-Diacetoxy-4-cycloh exylbu t-1-en e (a n ti-12b): 1H
NMR (300 MHz, CDCl3) δ 0.92-1.32 (m, 6H), 1.42-1.82 (m,
5H), 2.03 (s, 3H), 2.08 (s, 3H), 4.96 (dd, J ) 4.0/8.0 Hz, 1H),
5.32 (dt, J ) 1.4/10.4 Hz, 1H), 5.32 (dt, J ) 1.4/10.4 Hz, 1H),
5.36 (dt, J ) 1.4/17.3 Hz, 1H), 5.43 (broad dd, J ≈ 4.2/7.7 Hz,
1H), 5.85 (ddd, J ) 7.7/10.4/17.4 Hz, 1H).
a n ti-4-Cycloh exyl-4-acetoxybu t-1-en -3-ol (a n ti-15b): 1H
NMR (300 MHz, CDCl3) δ 0.99-1.31 (m, 6H), 1.61-1.84 (m,
5H), 2.09 (s, 3H), 4.25-4.36 (m, 1H), 4.80 (dd, J ) 4.4/7.0 Hz,
1H), 5.24 (dt, J ) 1.3/10.5 Hz, 1H), 5.33 (dt, J ) 1.1/17.0 Hz,
1H), 5.89 (ddd, J ) 7.0/10.5/17.0 Hz, 1H); 13C NMR (50 MHz,
CDCl3) δ 21.1, 25.8, 26.0, 26.2, 28.0, 29.6, 38.5, 72.8, 80.3,
117.7, 136.3, 171.7.
C
10H18O2: C, 70.55; H, 10.66. Found: C, 70.58; H, 10.61.
syn -6-Meth ylh ep t-1-en e-3,4-d iol (syn -2c): 1H NMR (200
MHz, CDCl3) δ 0.92 (d, J ) 6.6 Hz, 3H), 0.96 (d, J ) 7.2 Hz,
3H), 1.12-1.37 (m, 2H), 1.72-1.95 (m, 1H), 2.14 (d, J ) 3.6
Hz, 1H), 2.23 (d, J ) 3.6 Hz, 1H), 5.20-5.43 (m, 2H), 5.88 (ddd,
J ) 6.0/10.5/17.5 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 21.5,
23.7, 24.4, 41.8, 72.4, 76.7, 117.0, 137.5. Anal. Calcd for
C8H16O2: C, 66.63; H, 11.18. Found: C, 66.55; H, 11.12.
a n ti-6-Meth ylh ep t-1-en e-3,4-d iol (a n ti-2c): 1H NMR
(200 MHz, CDCl3) δ 0.91 (d, J ) 7.2 Hz, 3H), 0.95 (d, J ) 7.0
Hz, 3H), 1.36-1.53 (m, 2H), 1.75-1.91 (m, 1H), 1.90 (d, J )
6.0 Hz, 1H), 2.07 (d, J ) 5.0 Hz, 1H), 5.23-5.41 (m, 2H), 5.93
(ddd, J ) 6.4/10.5/17.5 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ
21.8, 23.5, 24.4, 40.7, 72.1, 76.2, 117.2, 135.9. Anal. Calcd for
C8H16O2: C, 66.63; H, 11.18. Found: C, 66.57; H, 11.25.
syn -6-P h en ylh ex-1-en e-3,4-d iol (syn -2d ): 1H NMR (300
MHz, CDCl3) δ 1.73-1.86 (m, 2H), 2.08-2.17 (broad s, 1H),
2.19-2.27 (broad s, 1H), 2.62-2.70 (m, 1H), 2.80-2.89 (m, 1H),
3.41-3.54 (m, 1H), 3.90-3.99 (m, 1H), 5.23 (dt, J ) 1.5/10.5
Hz, 1H), 5.34 (dt, J ) 1.5/17.5 Hz, 1H), 5.83 (ddd, J ) 6.3/
10.5/17.5 Hz, 1H), 7.28-7.40 (m, 5H); 13C NMR (50 MHz,
CDCl3) δ 31.8, 34.5, 73.6, 76.4, 117.5, 125.7, 128.2, 128.3, 137.3,
141.7. Anal. Calcd for C12H16O2: C, 74.97; H, 8.39. Found: C,
74.93; H, 8.44.
a n ti-1-Cycloh exyl-2-a cetoxybu t-3-en -1-ol (a n ti-9b): 1H
NMR (300 MHz, CDCl3) δ 0.94-1.47 (m, 6H), 1.61-1.84 (m,
4H), 1.93-2.03 (m, 1H), 2.11 (s, 3H), 3.46-3.53 (m, 1H), 5.33-
5.43 (m, 3H), 5.92 (ddd, J ) 7.0/10.7/17.7 Hz, 1H); 13C NMR
(50 MHz, CDCl3) δ 21.2, 25.7, 25.8, 28.3, 28.9, 39.6, 75.6, 76.4,
119.5, 131.7, 169.7. Anal. Calcd for C12H20O3: C, 67.89; H, 9.50.
Found: C, 67.83; H, 9.54.
Hyd r oxya llyla tion Rea ction Usin g In d iu m in THF /
H2O (p H ) 3). Typ ica l P r oced u r e (B). 3-Bromopropenyl
acetate 5 (0.175 mL, 1.5 mmol) was added at 0 °C to a
suspension of indium powder (0.115 g, 1 mmol) in THF (2 mL).
The heterogeneous mixture was stirred for 5 min at 0 °C, the
ice bath was removed, and stirring was continued for 40 min
at rt. Phthalate buffer (pH ) 3, 0.200 mL) was added at rt
followed by benzaldehyde (0.105 mL, 1 mmol) and the reaction
mixture was stirred for 45 min. Water was added (0.5 mL),
and the reaction mixture was stirred for 5 min and filtered
(Celite). The aqueous layer was extracted with ether, and the
combined organic layers were dried (Na2SO4) and evaporated
at reduced pressure. Purification by flash chromatography on
SiO2 (cyclohexane/ethyl acetate 9:1) afforded 0.033 g of anti-
9a (0.16 mmol, 16%) and 0.156 g of a 8:36:56 mixture of anti-
9a (0.012 g, 0.06 mmol, 6%), syn-9a (0.057 g, 0.28 mmol, 28%),
and syn-15a (0.087 g, 0.42 mmol, 42%). The overall isolated
yield was 92%.
a n ti-6-P h en ylh ex-1-en e-3,4-d iol (a n ti-2d ): 1H NMR (300
MHz, CDCl3) δ 1.67-1.80 (m, 2H), 1.92-2.03 (broad s, 2H),
2.60-2.75 (m, 1H), 2.79-2.91 (m, 1H), 3.65-3.75 (m, 1H),
4.04-4.14 (m, 1H), 5.26 (m, 1H), 5.32 (dt, J ) 1.5/17.5 Hz,
J . Org. Chem, Vol. 68, No. 3, 2003 1003

Lombardo et al.
1H), 5.90 (ddd, J ) 6.3/10.5/17.5 Hz, 1H), 7.28-7.42 (m, 5H);
13C NMR (50 MHz, CDCl3) δ 32.1, 33.6, 73.3, 76.0, 117.5, 128.8,
128.2, 128.3, 135.8, 141.8. Anal. Calcd for C12H16O2: C, 74.97;
H, 8.39. Found: C, 75.06; H, 8.46.
syn -(E)-1-P h en ylh exa -1,5-d ien e-3,4-d iol (syn -2e): 1H
NMR (300 MHz, CDCl3) δ 2.18 (d, J ) 3.0 Hz, 1H), 2.21 (d, J
) 3.0 Hz, 1H), 4.04-4.08 (m, 1H), 4.09-4.12 (m, 1H), 5.28 (dt,
J ) 1.5/10.5 Hz, 1H), 5.42 (dt, J ) 1.5/17.5 Hz, 1H), 5.94 (ddd,
J ) 5.7/10.5/17.5 Hz, 1H), 6.21 (dd, J ) 6.3/15.9 Hz, 1H), 6.70
(d, J ) 15.9 Hz, 1H), 7.21-7.42 (m, 5H); 13C NMR (50 MHz,
CDCl3) δ 75.6, 75.9, 117.4, 126.5, 127.9, 128.3, 132.6, 135.9,
136.5. Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C,
75.83; H, 7.47.
a n ti-(E)-1-P h en ylh exa -1,5-d ien e-3,4-d iol (a n ti-2e): 1H
NMR (300 MHz, CDCl3) δ 2.07 (d, J ) 3.2 Hz, 1H), 2.10 (d, J
) 3.0 Hz, 1H), 4.12-4.16 (m, 1H), 4.18-4.21 (m, 1H), 5.31 (dt,
J ) 1.5/10.5 Hz, 1H), 5.40 (dt, J ) 1.5/17.5 Hz, 1H), 5.95 (ddd,
J ) 6.3/10.5/17.5 Hz, 1H), 6.24 (dd, J ) 6.3/15.9 Hz, 1H), 6.68
(d, J ) 15.9 Hz, 1H), 7.20-7.40 (m, 5H); 13C NMR (50 MHz,
CDCl3) δ 75.3, 75.7, 117.7, 126.9, 127.3, 127.5, 132.8, 135.6,
136.3. Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C,
75.71; H, 7.38.
1.5/17.2 Hz, 1H), 5.74 (ddd, J ) 5.5/10.5/17.2 Hz, 1H), 6.85-
6.95 (m, 2H), 7.25-7.34 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
55.8, 77.6, 77.8, 114.3, 117.6, 128.8, 132.9, 136.9, 159.8. Anal.
Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C, 68.08; H,
7.34.
a n ti-1-(4-Met h oxyp h en yl)b u t -3-en e-1,2-d iol (a n ti-2i):
1H NMR (200 MHz, CDCl3) δ 1.92 (d, J ) 4.7 Hz, 1H), 2.27 (d,
J ) 3.7 Hz, 1H), 3.82 (s, 3H), 4.21-4.28 (m, 1H), 4.70 (broad
t, J ∼ 3.4 Hz, 1H), 5.25 (dt, J ) 1.4/10.5 Hz, 1H), 5.27 (ddd, J
) 1.5/17.2 Hz, 1H), 5.85 (ddd, J ) 6.2/10.5/17.2 Hz, 1H), 6.83-
6.95 (m, 2H), 7.24-7.34 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
55.8, 77.7, 78.3, 114.3, 118.2, 128.5, 132.5, 136.6, 159.7. Anal.
Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C, 68.11; H,
7.21.
syn -Dec-1-en e-3,4-diol (syn -2j): 1H NMR (300 MHz, CDCl3)
δ 0.89 (broad t, J ∼ 7.2 Hz, 3H), 1.24-1.37 (m, 7H), 1.37-
1.57 (m, 3H), 2.17 (broad s, 1H), 2.22 (broad s, 1H), 3.43-3.54
(m, 1H), 3.90-3.98 (m, 1H), 5.26 (dt, J ) 1.3/10.7 Hz, 1H),
5.32 (dt, J ) 1.4/17.0 Hz, 1H), 5.88 (ddd, J ) 6.4/10.7/17.0 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 14.0, 22.6, 25.5, 29.7, 31.7,
32.9, 74.4, 76.2, 117.3, 137.8. Anal. Calcd for C10H20O2: C,
69.72; H, 11.70. Found: C, 69.66; H, 11.74.
syn -2-Meth yl-h exa -1,5-d ien e-3,4-d iol (syn -2f): 1H NMR
(300 MHz, CDCl3) δ 1.78 (s, 3H), 2.25 (d, J ) 3.1 Hz, 1H),
2.34 (d, J ) 3.1 Hz, 1H), 3.91-3.99 (m, 1H), 4.10-4.21 (m,
1H), 4.99-5.05 (m, 1H), 5.06-5.07 (m, 1H), 5.25 (dt, J ) 1.4/
10.5 Hz, 1H), 5.39 (dq, J ) 1.4/17.1 Hz, 1H), 5.87 (ddd, J )
5.7/10.5/17.1 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 18.6, 73.7,
78.4, 113.8, 116.8, 136.7, 143.7. Anal. Calcd for C7H12O2: C,
65.60; H, 9.44. Found: C, 65.68; H, 9.40.
a n ti-Dec-1-en e-3,4-d iol (a n ti-2j): 1H NMR (300 MHz,
CDCl3) δ 0.89 (broad t, J ) 7.2 Hz, 3H), 1.24-1.37 (m, 7H),
1.37-1.57 (m, 3H), 1.94 (broad s, 1H), 2.07 (broad s, 1H), 3.64-
3.76 (m, 1H), 4.05-4.16 (m, 1H), 5.29 (dt, J ) 1.5/10.6 Hz,
1H), 5.35 (dt, J ) 1.4/17.0 Hz, 1H), 5.94 (ddd, J ) 6.3/10.6/
17.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 14.0, 22.6, 25.8,
29.3, 31.7, 32.1, 71.1, 76.0, 117.6, 136.1. Anal. Calcd for
C
10H20O2: C, 69.72; H, 11.70. Found: C, 69.78; H, 11.77.
a n ti-2-Meth ylh exa -1,5-d ien e-3,4-d iol (a n ti-2f): 1H NMR
(300 MHz, CDCl3) δ 1.63 (s, 3H), 2.05 (d, J ) 5.1 Hz, 1H),
2.09 (d, J ) 5.1 Hz, 1H), 4.01-4.05 (m, 1H), 4.18-4.27 (m,
1H), 5.29 (dt, J ) 1.7/10.5 Hz, 1H), 5.40 (dt, J ) 1.7/17.5 Hz,
1H), 5.91 (ddd, J ) 6.0/10.5/17.5 Hz, 1H); 13C NMR (50 MHz,
CDCl3) δ 18.8, 76.4, 77.8, 113.0, 117.6, 135.9, 143.6. Anal.
Calcd for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.54; H, 9.38.
syn -1-(2-F u r yl)bu t-3-en e-1,2-d iol (syn -2g): 1H NMR (200
MHz, CDCl3) δ 2.54 (s, 1H), 2.75 (s, 1H), 4.43-4.51 (m, 1H),
4.56 (dd, J ) 5.0/7.0 Hz, 1H), 5.22 (dt, J ) 1.8/10.5 Hz, 1H),
5.35 (dt, J ) 1.8/17.2 Hz, 1H), 5.80 (ddd, J ) 5.2/10.5/17.2 Hz,
1H), 6.33-6.39 (m, 2H), 7.40-7.43 (m, 1H); 13C NMR (50 MHz,
CDCl3) δ 70.9, 74.5, 108.0, 110.1, 117.1, 135.8, 142.1, 153.0.
Anal. Calcd for C8H10O3: C, 62.33; H, 6.54. Found: C, 62.39;
H, 6.47.
a n ti-1-(2-F u r yl)bu t-3-en e-1,2-d iol (a n ti-2g): 1H NMR
(200 MHz, CDCl3) δ 4.40-4.46 (m, 1H), 4.75 (t, J ) 5.4 Hz,
1H), 5.23 (dt, J ) 1.4/10.5 Hz, 1H), 5.39 (dt, J ) 1.4/17.2 Hz,
1H), 5.87 (ddd, J ) 5.6/10.5/17.2 Hz, 1H), 6.32-6.39 (m, 2H),
7.40-7.42 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 70.7, 74.7,
107.7, 110.1, 117.4, 135.6, 117.4, 135.6, 141.9, 153.0. Anal.
Calcd for C8H10O3: C, 62.33; H, 6.54. Found: C, 62.36; H, 6.59.
syn -1-(4-Meth ylp h en yl)bu t-3-en e-1,2-d iol (syn -2h ): 1H
NMR (300 MHz, CDCl3) δ 2.36 (s, 3H), 4.24 (ddt, J ) 1.5/5.4/
6.9 Hz, 1H), 4.49 (d, J ) 6.9 Hz, 1H), 5.16 (dt, J ) 1.6/10.6
Hz, 1H), 5.28 (dt, J ) 1.6/17.4 Hz, 1H), 5.75 (ddd, J ) 5.4/
10.6/17.4 Hz, 1H), 7.14-7.21 (m, 2H), 7.22-7.29 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 21.2, 77.0, 77.6, 116.9, 127.1, 129.1,
136.6, 137.5, 137.8. Anal. Calcd for C11H14O2: C, 74.13; H, 7.92.
Found: C, 74.18; H, 7.96.
a n ti-1-(4-Meth ylp h en yl)bu t-3-en e-1,2-d iol (a n ti-2h ): 1H
NMR (300 MHz, CDCl3) δ 2.36 (s, 3H), 4.32 (ddt, J ) 1.3/5.1/
6.2 Hz, 1H), 4.72 (d, J ) 5.1 Hz, 1H), 5.25 (dt, J ) 1.4/10.4
Hz, 1H), 5.32 (dt, J ) 1.4/17.1 Hz, 1H), 5.84 (ddd, J ) 6.2/
10.4/17.1 Hz, 1H), 7.15-7.21 (m, 2H), 7.22-7.30 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 29.8, 76.5, 76.8, 117.7, 126.8, 129.0,
136.1, 137.0, 137.6. Anal. Calcd for C11H14O2: C, 74.13; H, 7.92.
Found: C, 74.06; H, 7.98.
syn -1-(4-Meth oxyp h en yl)bu t-3-en e-1,2-d iol (syn -2i): 1H
NMR (200 MHz, CDCl3) δ 2.40 (d, J ) 3.4 Hz, 1H), 2.59 (d, J
) 2.6 Hz, 1H), 3.82 (s, 3H), 4.20-4.29 (m, 1H), 4.48 (dd, J )
2.6/7.3 Hz, 1H), 5.16 (dt, J ) 1.4/10.5 Hz, 1H), 5.27 (ddd, J )
Syn th esis of 2,2-Dim eth yl-4-p h en yl-5-eth en yl-1,3-d i-
oxola n e 16a . Typ ica l P r oced u r e. A catalytic amount of
Amberlyst-15H (10 mg) was added to a solution of freshly
distilled 2,2-dimethoxypropane (0.210 mL, 1.72 mmol) and
1-phenylbut-3-ene-1,2-diol 2a (0.141 g, 0.86 mmol, anti/syn )
25:75) in CH2Cl2 (5 mL). The reaction mixture was stirred at
rt overnight and filtered (Celite), and the organic layer was
evaporated at reduced pressure. Purification by flash-chro-
matography on SiO2 (cyclohexane/ethyl ether 98:2) afforded
0.129 g of trans-16a (0.63 mmol, 73%) and 0.043 g of cis-16a
(0.21 mmol, 24%).
4,5-t r a n s-2,2-D im e t h y l-4-p h e n y l-5-e t h e n y l-1,3-d i-
oxola n e (tr a n s-16a ): 1H NMR (200 MHz, CDCl3) δ 1.55 (s,
3H), 1.60 (s, 3H), 4.19 (t, J ) 8.4 Hz, 1H), 4.67 (d, J ) 8.4 Hz,
1H), 5.21-5.24 (m, 1H), 5.29-5.31 (m, 1H), 5.89 (ddd, J ) 6.8/
9.8/17.6 Hz, 1H), 7.25-7.42 (m, 5H); 13C NMR (50 MHz, CDCl3)
δ 27.08, 27.13, 82.9, 84.7, 109.2, 119.3, 126.4, 128.1, 128.4,
133.8, 137.1. Anal. Calcd for C13H16O2: C, 76.44; H, 7.90.
Found: C, 76.48; H, 7.86.
4,5-cis-2,2-Dim e t h yl-4-p h e n yl-5-e t h e n yl-1,3-d ioxo-
la n e (cis-16a ): 1H NMR (200 MHz, CDCl3) δ 1.53 (s, 3H), 1.70
(s, 3H), 4.83 (t, J ) 7.0 Hz, 1H), 5.00 (dd, J ) 2.2/7.0 Hz, 1H),
5.22-5.25 (m, 1H), 5.28-5.34 (m, 1H), 5.89 (ddd, J ) 6.8/9.9/
17.1 Hz, 1H), 7.25-7.40 (m, 5H); 13C NMR (50 MHz, CDCl3) δ
25.1, 27.4, 80.2, 80.7, 108.8, 117.8, 126.8, 128.0, 128.1, 134.9,
137.3. Anal. Calcd for C13H16O2: C, 76.44; H, 7.90. Found: C,
76.43; H, 7.94.
4,5-tr a n s-2,2-Dim et h yl-4-et h en yl-5-cycloh exyl-1,3-d i-
oxola n e (tr a n s-16b): 1H NMR (300 MHz, CDCl3) δ 0.80-
1.80 (m, 10H), 1.41 (broad s, 6H), 1.82-1.92 (m, 1H), 3.52 (dd,
J ) 6.0/7.4 Hz, 1H), 4.19 (t, J ) 7.4 Hz, 1H), 5.24 (dt, J )
1.2/10.2, 1H), 5.37 (dt, J ) 1.2/16.5, 1H), 5.88 (ddd, J ) 7.5/
10.2/16.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 26.0, 26.2, 27.2,
27.4, 29.3, 29.7, 30.0, 40.6, 80.6, 85.1, 108.8, 118.6, 136.9. Anal.
Calcd for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.28; H,
10.51.
4,5-cis-2,2-Dim et h yl-4-et h en yl-5-cycloh exyl-1,3-d iox-
ola n e (cis-16b): 1H NMR (300 MHz, CDCl3) δ 0.80-1.80 (m,
10H), 1.35 (s, 3H), 1.45 (s, 3H), 1.95-2.02 (m, 1H), 3.79 (dd, J
) 5.7/8.8 Hz, 1H), 4.41 (dd, J ) 5.4/8.8 Hz, 1H), 5.20-5.32
(m, 1H), 5.28-5.34 (m, 1H), 5.88 (ddd, J ) 8.4/10.2/18.3 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 25.77, 25.80, 26.0, 26.7, 28.6,
1004 J . Org. Chem., Vol. 68, No. 3, 2003

3-Bromopropenyl Esters in Organic Synthesis
29.0, 30.6, 37.4, 80.0, 82.7, 108.1, 118.4, 135.0. Anal. Calcd
for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.29; H, 10.58.
4,5-tr a n s-2,2-Dim eth yl-4-eth en yl-5-(2′-m eth ylp r op yl)-
1,3-d ioxola n e (tr a n s-16c): 1H NMR (200 MHz, CDCl3) δ 0.97
(d, J ) 6.6 Hz, 6H), 1.25-1.60 (m, 2H), 1.44 (broad s, 6H),
1.65-1.85 (m, 1H), 3.76 (dt, J ) 3.9/8.3 Hz, 1H), 3.96 (t, J )
8.3 Hz, 1H), 5.22-5.30 (m, 1H), 5.33-5.44 (m, 1H), 5.80 (ddd,
J ) 8.3/10.2/17.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 22.2,
25.4, 27.0, 27.4, 28.4, 29.7, 40.9, 78.9, 83.2, 108.4, 118.6, 135.3.
Anal. Calcd for C11H20O2: C, 71.70; H, 10.94. Found: C, 71.66;
H, 10.97.
(50 MHz, CDCl3) δ 15.3, 25.2, 27.5, 65.8, 79.6, 108.6, 112.0,
117.9, 134.3, 140.6. Anal. Calcd for C10H16O2: C, 71.39; H, 9.59.
Found: C, 71.45; H, 9.64.
4,5-t r a n s-2,2-Dim e t h yl-4-fu r yl-5-e t h e n yl-1,3-d ioxo-
la n e (tr a n s-16g): 1H NMR (200 MHz, CDCl3) δ 1.51 (s, 3H),
1.55 (s, 3H), 4.59-4.72 (m, 2H), 5.26 (ddd, J ) 1.4/10.3 Hz,
1H), 5.34 (ddd, J ) 1.4/17.2 Hz, 1H), 5.87 (ddd, J ) 6.0/10.3/
17.2 Hz, 1H), 6.34-6.41 (m, 2H), 7.45 (d, J ) 1.8 Hz, 1H); 13
C
NMR (50 MHz, CDCl3) δ 26.7, 27.0, 76.3, 80.5, 109.2, 109.6,
110.2, 119.0, 133.8, 143.2, 150.0. Anal. Calcd for C11H14O3: C,
68.02; H, 7.27. Found: C, 68.06; H, 7.21.
4,5-cis-2,2-Dim eth yl-4-fu r yl-5-eth en yl-1,3-dioxolan e (cis-
16g): 1H NMR (200 MHz, CDCl3) δ 1.47 (s, 3H), 1.64 (s, 3H),
4.62 (d, J ) 6.7 Hz, 1H), 4.77 (t, J ) 6.7 Hz, 1H), 5.15 (ddd, J
) 1.8/10.3 Hz, 1H), 5.31 (ddd, J ) 1.8/17.2 Hz, 1H), 5.82-
4,5-cis-2,2-Dim eth yl-4-eth en yl-5-(2′-m eth ylp r op yl)-1,3-
d ioxola n e (cis-16c): 1H NMR (200 MHz, CDCl3) δ 0.96 (d, J
) 6.6 Hz, 6H), 1.09-1.32 (m, 1H), 1.40 (s, 3H), 1.45-1.56 (m,
1H), 1.51 (s, 3H), 1.65-1.87 (m, 1H), 4.26 (ddd, J ) 4.3/6.2/
9.6 Hz, 1H), 4.49 (dd, J ) 6.2/7.3 Hz, 1H), 5.20-5.27 (m, 1H),
5.28-5.36 (m, 1H), 5.84 (ddd, J ) 7.3/10.0/17.2 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 22.0, 23.5, 25.1, 25.8, 28.4, 39.1, 76.3,
80.0, 107.9, 117.9, 134.6. Anal. Calcd for C11H20O2: C, 71.70;
H, 10.94. Found: C, 71.77; H, 10.97.
4,5-tr a n s-2,2-Dim et h yl-4-et h en yl-5-(2′-p h en ylet h yl)-
1,3-d ioxola n e (tr a n s-16d ): 1H NMR (300 MHz, CDCl3) δ 1.44
(s, 3H), 1.46 (s, 3H), 1.82-1.96 (m, 2H), 2.62-2.75 (m, 1H),
2.78-2.84 (m, 1H), 3.72 (dt, J ) 5.7/8.0 Hz, 1H), 4.07 (t, J )
8.0 Hz, 1H), 5.25 (dt, J ) 1.1/10.4 Hz, 1H), 5.35 (dt, J ) 1.1/
17.0 Hz, 1H), 5.80 (ddd, J ) 7.3/10.4/17.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 27.0, 27.3, 32.3, 33.6, 79.9, 82.7, 108.6,
118.9, 125.8, 128.3, 128.4, 135.3, 141.7. Anal. Calcd for
5.86 (m, 1H), 6.26-6.35 (m, 2H), 7.40 (d, J ) 1.8 Hz, 1H); 13
C
NMR (50 MHz, CDCl3) δ 25.3, 27.2, 74.6, 80.0, 108.6, 109.4,
110.0, 118.0, 133.3, 142.4, 149.8. Anal. Calcd for C11H14O3: C,
68.02; H, 7.27. Found: C, 67.94; H, 7.31.
4,5-tr a n s-2,2-Dim et h yl-4-(4-m et h ylp h en yl)-5-et h en yl-
1,3-d ioxola n e (tr a n s-16h ): 1H NMR (200 MHz, CDCl3) δ 1.56
(s, 3H), 1.61 (s, 3H), 2.37 (s, 3H), 4.20 (broad t, J ) 7.5 Hz,
1H), 4.65 (d, J ) 8.3 Hz, 1H), 5.19-5.35 (m, 2H), 5.90 (ddd, J
) 7.1/10.1/17.6 Hz, 1H), 7.14-7.23 (m, 2H), 7.24-7.32 (m, 2H);
13C NMR (50 MHz, CDCl3) δ 21.2, 27.1, 82.8, 84.6, 109.1, 119.0,
126.4, 129.0, 133.9, 135.0, 137.8. Anal. Calcd for C14H18O2: C,
77.03; H, 8.31. Found: C, 77.13; H, 8.38.
4,5-cis-2,2-Dim eth yl-(4-m eth ylp h en yl)-5-eth en yl-1,3-d i-
oxola n e (cis-16h ): 1H NMR (200 MHz, CDCl3) δ 1.53 (s, 3H),
1.69 (s, 3H), 2.36 (s, 3H), 4.81 (broad t, J ∼ 7.1 Hz, 1H), 4.65
(broad dd, J ) 1.0/2.5/6.8 Hz, 1H), 5.20-5.35 (m, 2H), 5.87
(ddd, J ) 7.1/10.3/17.2 Hz, 1H), 7.16-7.23 (m, 2H), 7.24-7.30
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 25.0, 27.5, 80.1, 80.7,
108.6, 117.7, 126.7, 128.7, 134.0, 134.3, 138.0. Anal. Calcd for
C
15H20O2: C, 77.55; H, 8.68. Found: C, 77.50; H, 8.63.
4,5-Cis-2,2-Dim et h yl-4-et h en yl-5-(2′-p h en ylet h yl)-1,3-
d ioxola n e (cis-16d ): 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
3H), 1.53 (s, 3H), 1.63-1.75 (m, 1H), 1.76-1.92 (m, 1H), 2.65
(ddd, J ) 6.9/9.8/13.7 Hz, 1H), 2.82 (ddd, J ) 5.2/10.1/13.7
Hz, 1H), 4.16 (ddd, J ) 4.6/6.3/10.7 Hz, 1H), 4.50 (t, J ) 6.3
Hz, 1H), 5.23 (ddd, J ) 0.8/1.6/10.3 Hz, 1H), 5.31 (dt, J ) 1.5/
17.1 Hz, 1H), 5.83 (ddd, J ) 7.8/10.3/17.1 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 25.7, 28.3, 32.4 (2C), 77.4, 79.7, 108.2, 118.2,
125.8, 128.3, 128.4, 134.3, 141.6. Anal. Calcd for C15H20O2: C,
77.55; H, 8.68. Found: C, 77.61; H, 8.74.
C
14H18O2: C, 77.03; H, 8.31. Found: C, 77.09; H, 8.25.
4,5-tr a n s-2,2-Dim eth yl-4-(4-m eth oxyp h en yl)-5-eth en yl-
1,3-d ioxola n e (tr a n s-16i): 1H NMR (300 MHz, CDCl3) δ 1.55
(s, 3H), 1.60 (s, 3H), 3.82 (s, 3H), 4.19 (broad t, J ∼ 8.2 Hz,
1H), 4.63 (d, J ) 8.2 Hz, 1H), 5.21-5.30 (m, 2H), 5.88 (ddd, J
) 7.1/10.3/17.4 Hz, 1H), 6.92 (d, J ) 9.4, 2H), 7.31 (d, J ) 9.4,
2H); 13C NMR (50 MHz, CDCl3) δ 27.1, 55.2, 82.7, 84.5, 109.0,
113.8, 119.0, 127.7, 129.0, 133.9, 159.8. Anal. Calcd for
4,5-tr a n s-2,2-Dim eth yl-4-(2′-p h en yleth en yl)-5-eth en yl-
1,3-d ioxola n e (tr a n s-16e): 1H NMR (300 MHz, CDCl3) δ 1.48
(s, 3H), 1.50 (s, 3H), 4.18 (t, J ) 6.9 Hz, 1H), 4.27 (dd, J )
6.9/7.1 Hz, 1H), 5.27 (dd, J ) 1.1/10.1 Hz, 1H), 5.38 (dd, J )
1.1/17.2 Hz, 1H), 5.85 (ddd, J ) 6.9/10.1/17.2 Hz, 1H), 6.15
(dd, J ) 7.1/15.6 Hz, 1H), 6.67 (d, J ) 15.6 Hz, 1H), 7.21-
7.44 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 27.07, 27.11, 82.1,
82.4, 109.2, 118.9, 125.0, 126.6, 127.9, 128.5, 133.9, 134.0,
136.2. Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C,
78.28; H, 7.81.
4,5-cis-2,2-Dim eth yl-4-(2′-p h en yleth en yl)-5-eth en yl-1,3-
d ioxola n e (cis-16e): 1H NMR (300 MHz, CDCl3) δ 1.44 (s,
3H), 1.58 (s, 3H), 4.67 (ddt, J ) 1.1/6.5/7.2 Hz, 1H), 4.79 (ddd,
J ) 0.9/6.5/7.7 Hz, 1H), 5.23 (ddd, J ) 0.8/1.7/10.5 Hz, 1H),
5.34 (dd, J ) 1.1/1.7/17.0 Hz, 1H), 5.81 (ddd, J ) 7.2/10.5/17.0
Hz, 1H), 6.11 (dd, J ) 7.7/16.0 Hz, 1H), 6.62 (d, J ) 16.0 Hz,
1H), 7.21-7.44 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 25.6,
28.1, 79.6, 80.1, 108.9, 118.2, 125.5, 126.6, 127.8, 128.5, 133.2,
134.3, 136.4. Anal. Calcd for C15H18O2: C, 78.23; H, 7.88.
Found: C, 78.25; H, 7.83.
4,5-tr a n s-2,2-Dim eth yl-4-(1′-m eth yleth en yl)-5-eth en yl-
1,3-d ioxola n e (tr a n s-16f): 1H NMR (200 MHz, CDCl3) δ 1.46
(s, 3H), 1.47 (s, 3H), 1.78 (t, J ) 0.8 Hz, 3H), 4.08-4.22 (m,
2H), 4.95-4.99 (m, 1H), 5.04-5.09 (m, 1H), 5.23-5.30 (m, 1H),
5.31-5.42 (m, 1H), 5.84 (ddd, J ) 5.9/10.3/17.3 Hz, 1H); 13C
NMR (50 MHz, CDCl3) δ 17.8, 26.9, 27.1, 81.0, 84.5, 109.0,
113.8, 118.8, 134.9, 140.7. Anal. Calcd for C10H16O2: C, 71.39;
H, 9.59. Found: C, 71.46; H, 9.53.
4,5-cis-2,2-Dim eth yl-4-(1′-m eth yleth en yl)-5-eth en yl-1,3-
d ioxola n e (cis-16f): 1H NMR (200 MHz, CDCl3) δ 1.42 (s, 3H),
1.56 (s, 3H), 1.67 (t, J ) 1.2 Hz, 3H), 4.58-4.67 (m, 2H), 4.91-
4.96 (m, 1H), 5.06-5.12 (m, 1H), 5.15-5.23 (m, 1H), 5.28-
5.34 (m, 1H), 5.84 (ddd, J ) 5.8/10.1/17.0 Hz, 1H); 13C NMR
C
14H18O3: C, 71.77; H, 7.74. Found: C, 71.77; H, 7.74.
4,5-cis-2,2-Dim et h yl-4-(4-m et h oxyp h en yl)-5-et h en yl-
1,3-d ioxola n e (cis-16i): 1H NMR (300 MHz, CDCl3) δ 1.51
(s, 3H), 1.68 (s, 3H), 3.83 (s, 3H), 4.79 (broad t, J ∼ 7.6 Hz,
1H), 5.02 (d, J ) 7.6 Hz, 1H), 5.19-5.28 (m, 2H), 5.87 (ddd, J
) 6.8/10.2/17.3 Hz, 1H), 6.88 (d, J ) 9.4, 2H), 7.21 (d, J ) 9.4,
2H); 13C NMR (50 MHz, CDCl3) δ 29.8, 55.2, 79.9, 80.6, 108.6,
113.7, 117.7, 128.0, 130.8, 135.0, 160.0. Anal. Calcd for
C
14H18O3: C, 71.77; H, 7.74. Found: C, 71.77; H, 7.74.
4,5-t r a n s-2,2-Dim e t h yl-4-h e xyl-5-e t h e n yl-1,3-d ioxo-
la n e (tr a n s-16j): 1H NMR (200 MHz, CDCl3) δ 0.90 (broad t,
J ∼ 6.7 Hz, 3H), 1.24-1.62 (m, 10H), 1.43 (s, 3H), 1.44 (s, 3H),
4.15 (dt, J ) 6.2/8.0 Hz, 1H), 4.49 (broad t, J ∼ 6.6 Hz, 1H),
5.26 (ddd, J ) 0.77/1.8/10.3 Hz, 1H), 5.38 (ddd, J ) 0.77/1.5/
17.2 Hz, 1H), 5.83 (ddd, J ) 7.3/10.3/17.2 Hz, 1H); 13C NMR
(50 MHz, CDCl3) δ 14.1, 22.7, 26.0, 26.9, 27.4, 80.7, 82.8, 108.3,
118.6, 135.5. Anal. Calcd for C13H24O2: C, 73.54; H, 11.39.
Found: C, 73.59; H, 11.46.
4,5-cis-2,2-Dim eth yl-4-h exyl-5-eth en yl-1,3-dioxolan e (cis-
16j): 1H NMR (200 MHz, CDCl3) δ; 13C NMR (50 MHz, CDCl3)
δ 0.91 (broad t, J ∼ 6.7 Hz, 3H), 1.24-1.60 (m, 10H), 1.39 (s,
3H), 1.51 (s, 3H), 3.69 (dt, J ) 5.8/8.5 Hz, 1H), 4.00 (broad t,
J ∼ 8.2 Hz, 1H), 5.24 (ddd, J ) 0.77/1.9/10.2 Hz, 1H), 5.31
(ddd, J ) 0.77/1.8/17.2 Hz, 1H), 5.84 (ddd, J ) 7.8/10.2/17.2
Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 14.1, 22.7, 25.7, 26.2,
28.3, 29.4, 30.4, 31.8, 78.3, 79.9, 107.9, 118.0, 134.6. Anal.
Calcd for C13H24O2: C, 73.54; H, 11.39. Found: C, 73.48; H,
11.45.
Hyd r oxya llyla tion Rea ction Usin g Zn in Aqu eou s
NH4Cl. Typ ica l P r oced u r e. Benzaldheyde (0.105 mL, 1
J . Org. Chem, Vol. 68, No. 3, 2003 1005

Lombardo et al.
mmol), 3-bromopropenyl acetate 5 (0.175 mL, 1.5 mmol), and
zinc powder (0.98 g, 1.5 mmol) were subsequently added at rt
to a saturated aqueous solution of NH4Cl (5 mL). The reaction
was quite exothermic, so temperature was controlled with a
water bath. Zinc powder almost completely dissolved in 2 min.
The reaction was checked after 15 min, the aqueous layer was
extracted with ether after 30 min. The combined organic layers
were dried (Na2SO4) and evaporated at reduced pressure.
Purification by flash chromatography on SiO2 (cyclohexane/
ethyl acetate 9:1) afforded 0.186 g of a 70:30 mixture of 9a
and 15a .
5.82 (ddd, J ) 6.2/9.9/17.4 Hz, 1H), 7.16 (br d, J ) 7.7 Hz,
2H), 7.27 (br d, J ) 7.7 Hz, 2H). The following signals in the
NMR spectra of crude reaction mixture are assigned to 15h :
1H NMR (200 MHz, CDCl3) δ 4.36-4.50 (m, 1H), 5.65 (d, J )
6.8 Hz, 1H); 13C NMR (300 MHz, CDCl3) δ 21.5, 77.3, 77.9,
117.2, 127.4, 129.4, 136.9, 137.7, 138.1. Anal. Calcd for
C
13H16O3: C, 70.89; H, 7.32. Found: C, 70.97; H, 7.41.
syn -1-(4-Meth oxyp h en yl)-2-a cetoxybu t-3-en -1-ol (syn -
9i): 1H NMR (200 MHz, CDCl3) δ 2.07 (s, 3H), 3.82 (s, 3H),
4.83 (d, J ) 4.8 Hz, 1H), 5.28 (dt, J ) 1.1/16.5 Hz, 1H), 5.29
(dt, J ) 1.1/10.3 Hz, 1H), 5.43 (ddt, J ) 1.1/4.8/6.6 Hz, 1H),
5.83 (ddd, J ) 6.6/10.3/16.5 Hz, 1H), 6.89 (br d, J ) 8.7 Hz,
2H), 7.30 (br d, J ) 8.7 Hz, 2H). The following signals in the
NMR spectra of crude reaction mixture are assigned to 15i:
1H NMR (200 MHz, CDCl3) δ 4.35-4.48 (m, 1H), 5.63 (d, J )
7.5 Hz, 1H); 13C NMR (200 MHz, CDCl3) δ 21.2, 55.5, 74.7,
78.1, 113.3, 119.6, 127.8, 131.5, 131.8, 159.2, 169.9. Anal. Calcd
for C13H16O4: C, 66.09; H, 6.83. Found: C, 66.15; H, 6.76.
a n ti-3-Acetoxydec-1-en -4-ol (a n ti-9j): 1H NMR (200 MHz,
CDCl3) δ 0.88 (broad t, J ∼ 7.3 Hz, 3H), 1.21-1.35 (m, 7H),
1.36-1.53 (m, 3H), 2.10 (s, 3H), 3.68-3.81 (m, 1H), 5.15-5.35
(m, 2H), 5.33-5.40 (m, 1H), 5.86 (ddd, J ) 7.0/10.3/17.5 Hz,
1H). The following signals in the NMR spectra of crude
reaction mixture are assigned to 15j: 1H NMR (200 MHz,
CDCl3) δ 4.08-4.25 (m, 1H), 4.82-5.02 (m, 1H); 13C NMR (50
MHz, CDCl3) δ 14.0, 21.2, 22.6, 25.6, 29.2, 31.7, 32.3, 72.6,
77.9, 119.3, 131.8, 170.1. Anal. Calcd for C12H22O3: C, 67.26;
H, 10.35. Found: C, 67.33; H, 10.29.
a n ti-3-Acet oxy-6-m et h ylh ep t -1-en -4-ol (a n ti-9c): 1H
NMR (200 MHz, CDCl3) δ 0.92 (d, J ) 6.7 Hz, 3H), 0.96 (d, J
) 6.7 Hz, 3H), 1.25 (dd, J ) 3.8/9.1 Hz, 1H), 1.36 (dd, J )
5.1/9.4 Hz, 1H), 1.74-1.89 (m, 1H), 2.12 (s, 3H), 3.79-3.92
(m, 1H), 5.13-5.43 (m, 3H), 5.87 (ddd, J ) 6.8/10.2/17.2 Hz,
1H). The following signals in the NMR spectra of crude
reaction mixture are assigned to 15c: 1H NMR (200 MHz,
CDCl3) δ 4.07-4.27 (m, 1H, syn + anti), 4.95-5.10 (m, 1H,
syn + anti).; 13C NMR (200 MHz, CDCl3) δ 21.2, 21.7, 23.5,
24.3, 41.2, 70.7, 78.3, 129.3, 130.8, 170.1. Anal. Calcd for
C
10H18O3: C, 64.49; H, 9.74. Found: C, 64.41; H, 9.81.
a n ti-3-Acet oxy-6-p h en ylh exen -1-en -4-ol (a n ti-9d ): 1H
NMR (200 MHz, CDCl3) δ 1.73-1.87 (m, 1H), 1.90-2.02 (m,
1H), 2.13 (s, 3H), 2.61-2.79 (m, 1H), 2.82-2.99 (m, 1H), 3.73-
3.87 (m, 1H), 5.18-5.47 (m, 3H), 5.88 (ddd, J ) 10.0/10.3/17.3
Hz, 1H), 7.16-7.39 (m, 5H). The following signals in the NMR
spectra of crude reaction mixture are assigned to 15d : 1H
NMR (200 MHz, CDCl3) _4.17-4.32 (m, 1H), 4.93-5.05 (m,
1H).; 13C NMR (200 MHz, CDCl3) δ 21.4, 32.1, 34.2, 72.1, 78.2,
119.7, 126.1, 128.5, 132.1, 141.8, 170.4. Anal. Calcd for
Equ ilibr a tion Exp er im en ts. A 1:1 mixture of syn-9a and
syn-15a (0.145 g, 0.7 mmol) was added at 25 °C to a solution
of 7 (1 mmol), prepared according to typical procedure A. After
the mixture was stirred at 25 °C for 40 min, water was added
(0.5 mL), and the reaction mixture was stirred for 5 min and
filtered (Celite). The aqueous layer was extracted with ether,
and the combined organic layers were dried (Na2SO4) and
evaporated at reduce pressure. The crude reaction mixture was
dissolved in MeOH/H2O (5 mL, 9:1 v/v), K2CO3 (0.415 g, 3
mmol) was added, and the reaction mixture was stirred at rt
overnight. MeOH was removed at reduced pressure and the
aqueous layer was extracted with ether. The combined organic
layers were dried (Na2SO4) and evaporated at reduce pressure.
1H NMR analysis of the crude reaction mixture revealed the
presence of pure syn-2a .
C
14H18O3: C, 71.77; H, 7.74. Found: C, 71.84; H, 7.79.
syn -(E)-1-P h en yl-4-a cetoxy-h exa -1,5-d ien -3-ol (syn -9e).
1H NMR (200 MHz, CDCl3) δ 2.14 (s, 3H), 4.26-4.52 (m, 1H),
5.28-5.48 (m, 3H), 5.77-6.01 (m, 1H), 6.19 (dd, J ) 6.2/15.8
Hz, 1H), 6.7 (d, J ) 15.8 Hz, 1H), 7.23-7.45 (m, 5H). The
following signals in the NMR spectra of crude reaction mixture
are assigned to 15e: (200 MHz, CDCl3) _3.75-3.79 (m, 1H),
5.23-5.27 (m, 1H).; 13C NMR (200 MHz, CDCl3) δ 21.1, 73.4,
73.9, 118.9, 119.2, 123.7, 126.4, 128.2, 131.9, 132.6, 134.5,
170.2. Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C,
72.31; H, 6.87.
2-Meth yl-4-a cetoxyh exa -1,5-d ien -3-ol (9f): 1H NMR (200
MHz, CDCl3) δ 1.80 (s, 3H), 2.12 (s, 3H), 4.15-4.36 (m, 1H),
A second experiment was carried out with an anti-enriched
1:1 mixture of 9a and 15a (190 mg, 0.9 mmol, syn/anti ) 33:
67). Again, 1H NMR analysis of the crude reaction mixture
revealed that 2a had preserved the same original 33:67 syn/
anti ratio.
4.95-5.14 (m, 2H), 5.18-5.46 (m, 3H), 5.72-5.96 (m, 1H); 13
C
NMR (200 MHz, CDCl3) δ 18.0, 21.1, 72.8, 73.8, 114.6, 119.0,
132.7, 135.8, 144.0, 170.2. Anal. Calcd for C9H14O3: C, 63.51;
H, 8.29. Found: C, 63.58; H, 8.34.
syn -1-F u r yl-2-a cetoxybu t-3-en -1-ol (syn -9g): 1H NMR
(200 MHz, CDCl3) δ 2.09 (s, 3H), 2.41 (d, J ) 5.9 Hz, 1H),
4.86 (broad t, J ∼ 5.3 Hz, 1H), 5.34 (dt, J ) 1.4/10.4 Hz, 1H),
5.38 (dt, J ) 1.4/17.4 Hz, 1H), 5.60 (ddt, J ) 1.2/4.8/6.3 Hz,
1H), 5.89 (ddd, J ) 6.3/10.4/17.4 Hz, 1H), 6.30-6.40 (m, 2H),
7.37-7.43 (m, 1H). The following signals in the NMR spectra
of crude reaction mixture are assigned to 15g: 1H NMR (200
MHz, CDCl3) δ 4.57-4.70 (m, 1H), 5.78 (d, J ) 7.3 Hz, 1H);
13C NMR (200 MHz, CDCl3) δ 21.1, 69.5, 76.0, 107.7, 110.2,
119.6, 131.7, 142.3, 152.4, 169.9. Anal. Calcd for C10H12O4: C,
61.22; H, 6.16. Found: C, 61.28; H, 6.22.
Ack n ow led gm en t. We thank Prof. Dieter Seebach
for valuable discussions and helpful suggestions. This
work was supported by MURST-Rome (National Project
“Stereoselezione in Sintesi Organica. Metodologie e
Applicazioni”) and University of Bologna (funds for
selected topics).
Note Ad d ed After ASAP P ostin g.
The Table of Contents graphic had an incorrect struc-
ture in the version posted J anuary 9, 2003; the correct
version was posted J anuary 10, 2003.
syn -1-(4-Met h ylp h en yl)-2-a cet oxyb u t -3-en -1-ol (syn -
9h ): 1H NMR (200 MHz, CDCl3) δ 2.08 (s, 3H), 2.35 (s, 3H),
4.86 (t, J ) 4.1 Hz, 1H), 5.28 (dt, J ) 1.4/17.4 Hz, 1H), 5.29
(dt, J ) 1.5/9.9 Hz, 1H), 5.46 (ddt, J ) 1.2/4.5/6.2 Hz, 1H),
J O0262457
1006 J . Org. Chem., Vol. 68, No. 3, 2003