Inter- and intramolecular pathways for the formation of tetrahydrofurans from β-(phosphatoxy)alkyl radicals. Evidence for a dissociative mechanism

Article abstract of DOI:10.1021/jo991570o

β-(Phosphatoxy)alkyl radicals generated by photolysis of Barton PTOC esters in the presence of allyl alcohol and tert-butyl mercaptan undergo nucleophilic substitution followed by 5-exo-trig radical ring closure leading to tetrahydrofurans in good yield and with high trans selectivity. β- (Phosphatoxy)alkyl radicals obtained by intramolecular hydrogen 1,5- abstraction with an alkoxyl radical undergo nucleophilic displacement providing tetrahydrofurans. The ensemble of results, including the effects of leaving groups and substituents, strongly support a dissociative mechanism for these radical nucleophilic displacement reactions.

Full text of DOI:10.1021/jo991570o

J . Org. Chem. 2000, 65, 523-529
523
In ter - a n d In tr a m olecu la r P a th w a ys for th e F or m a tion of
Tetr a h yd r ofu r a n s fr om â-(P h osp h a toxy)a lk yl Ra d ica ls. Evid en ce
for a Dissocia tive Mech a n ism
David Crich,*,† Xianhai Huang,† and Martin Newcomb*,‡
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois
60607, and Department of Chemistry, Wayne State University, Detroit, Michigan 48202
Received October 8, 1999
â-(Phosphatoxy)alkyl radicals generated by photolysis of Barton PTOC esters in the presence of
allyl alcohol and tert-butyl mercaptan undergo nucleophilic substitution followed by 5-exo-trig radical
ring closure leading to tetrahydrofurans in good yield and with high trans selectivity. â-(Phos-
phatoxy)alkyl radicals obtained by intramolecular hydrogen 1,5-abstraction with an alkoxyl radical
undergo nucleophilic displacement providing tetrahydrofurans. The ensemble of results, including
the effects of leaving groups and substituents, strongly support a dissociative mechanism for these
radical nucleophilic displacement reactions.
Sch em e 1
In tr od u ction
The vicinal displacement of a phosphate group from a
â-(phosphatoxy)alkyl radical by a nucleophile constitutes
a new and interesting class of reaction with potential for
incorporation into radical/polar crossover tandem se-
quences; it is the most recent addition to the reaction
manifold of â-ester-substituted radicals that also includes
rearrangements and heterolyses (Scheme 1).1 This gen-
eral class of nucleophilic substitutions was first recog-
nized by Zipse, who predicted that the degenerate, vicinal
displacement of chloride from the â-chloroethyl radical
by chloride anion would be a concerted process involving
backside attack (Scheme 2).2-4 The first actual example
of this class of reactions was realized in these laboratories
and involved the reaction of octanol with the 1-(diphe-
nylphosphatoxy)-2-methyl-1-phenyl-2-propyl radical (2)
under laser flash photolytic conditions with an apparent
bimolecular rate constant of 2 × 106 M-1‚s-1 at 20 °C
(Scheme 3).5 In a preparative experiment conducted in
the presence of tert-butyl thiol, the ether 4 could be
isolated in 60% yield.5 No evidence was found for the
formation of the regioisomeric product octyl 1-phenyl-2-
methylpropyl ether, which provided some support for a
concerted vicinal displacement. First generation stereo-
chemical probes revealed the substitution to be only
moderately stereoselective.6 This low stereoselectivity
raised the possibility of either a Zipse-type concerted
process with attack on either lobe of the initial, singly
occupied orbital in 2 or a dissociative mechanism with
attack on a contact ion pair.6 Very recent work from our
laboratories has provided strong evidence in favor of the
companion reaction, the â-(phosphatoxy)alkyl rearrange-
ment1 being dissociative in nature with the precise
Sch em e 2
Sch em e 3
outcome being dependent on the partitioning between
contact and solvent separated ion pairs.7,8
In this paper, we describe in full our initial studies
aimed at exploring the preparative potential of this class
of reactions, especially with respect to the formation of
tetrahydrofurans,9 from which we also deduce strong
support for the dissociative pathway.
Resu lts a n d Discu ssion
† University of Illinois at Chicago.
‡ Wayne State University.
We reasoned that an elementary radical/polar cross-
over sequence could be set up by the use of allyl alcohol
(1) Beckwith, A. L. J .; Crich, D.; Duggan, P. J .; Yao, Q. Chem. Rev.
1997, 97, 3273.
(2) Zipse, H. Angew. Chem., Int. Ed. Engl. 1994, 33, 1985.
(3) Zipse, H. J . Chem. Soc., Perkin Trans. 2 1997, 2691.
(4) Zipse, H. Acc. Chem. Res. 1999, 32, 571.
(5) Choi, S.-Y.; Crich, D.; Horner, J . H.; Huang, X.; Martinez, F. N.;
Newcomb, M.; Wink, D. J .; Yao, Q. J . Am. Chem. Soc. 1998, 120, 211.
(6) Crich, D.; Gastaldi, S. Tetrahedron Lett. 1998, 39, 9377.
(7) Whitted, P. O.; Horner, J . H.; Newcomb, M.; Huang, X.; Crich,
D. Org. Lett. 1999, 1, 153.
(8) Newcomb, M.; Horner, J . H.; Whitted, P. O.; Crich, D.; Huang,
X.; Yao, Q.; Zipse, H. J . Am. Chem. Soc. 1999, 121, 10685.
(9) Crich, D.; Huang, X.; Newcomb, M. Org. Lett. 1999, 1, 225.
10.1021/jo991570o CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/29/1999

524 J . Org. Chem., Vol. 65, No. 2, 2000
Crich et al.
Sch em e 4
Sch em e 5
Ta ble 1. In ter m olecu la r Rea ction of
â-(P h osp h a toxy)a lk yl Ra d ica ls w ith Allyl Alcoh ol
substrate product (% yield)a
substrate product (% yield)a
1
5 (82) t/c ) 90/10
5 (85) t/c ) 90/10
18a (78) t/c ) 94/6
18b (75) t/c ) 88/12
17c
10b
17d
17e
18c (92) t/c ) 85/15
19 (67)
20a (90)
10a
17a
17b
20b (85)
Sch em e 6
a
Yields refer to isolated mixtures of diastereomers with the
ratios established by NMR.
as nucleophile in the vicinal displacement sequence. In
the anticipated sequence the â-(phosphatoxy)alkyl radical
undergoes vicinal nucleophilic substitution leading to a
1-phenyl-3-oxa-5-hexenyl radical, which should undergo
rapid, 5-exo-cyclization with formation of a (tetrahydro-
furanyl)methyl radical. Allyl alcohol had previously been
used in a similar context to trap the radical cation arising
from fragmentation of a nucleotide C4′ radical by the
Giese group.10 In the event, white light photolysis of the
O-acyl thiohydroxamate 1 in allyl alcohol, in the presence
of tert-butyl thiol as chain-transfer agent, led to the
isolation of two stereoisomeric tetrahydrofurans (5) in
82% combined yield and a 9/1 ratio. It was readily
are in equilibrium via a â-(phosphatoxy)alkyl migration
and that such a migration precedes the substitution
process in the case of radical 2.12 The remote possibility
that 5 could be formed from 10a , via elimination of
diphenyl phosphate to give 14, Michael addition of allyl
alcohol, affording 15, and eventual decarboxylative cy-
clization, was eliminated from consideration when an
authentic sample of 14 failed to yield any 5 under the
standard reaction conditions. Presumably, the highly
regioselective nature of the capture of radical cation 12
reflects the considerably higher (∼8 kcal‚mol-1) radical
stabilization energy of a secondary benzyl radical over
of a tert-alkyl radical.13
1
apparent from the H-spectral data that the two tetrahy-
drofurans had the indicated regiochemistry; NOE studies
led to the assignment of the major isomer as the trans
diastereomer. No evidence was found for the formation
of the regioisomeric products (6). Given the high regio-
selectivity of the reaction set out in Scheme 3 and the
known trans selectivity of the 1-phenyl-5-hexenyl radical
itself,11 this particular result was unexceptional.
The regioisomeric O-acyl thiohydroxamate (10a ) was
prepared, as outlined in Scheme 4,8 in the expectation
that a concerted vicinal displacement on the derived
radical by allyl alcohol would lead to the tetrahydrofuran
6. However, it soon became apparent that the only cyclic
products, isolated in 85% yield, were a 9/1 trans/cis
mixture of the stereoisomers of 5. Hence, both regioiso-
meric substrates 1 and 10a led to the same product in
comparable yield and with comparable stereoselectivity
(Table 1). It is therefore highly likely that both reactions
proceed via common intermediates and that these inter-
mediates are the radical cation/phosphate anion pair 12
and the benzylic oxahexenyl radical 13 (Scheme 5). We
cannot exclude the possibility that radicals 2 and 11a
A series of experiments were conducted with para-
substituted analogues of 1, prepared as illustrated in
Scheme 6, leading to the results set out in Table 1.
Electron-withdrawing substituents generally resulted in
clean reactions, good to excellent yields, and high trans
selectivity for the ring closure in excellent agreement
with the observations from the parent compound (1). It
was not possible to make a direct comparison with the
(12) The rate constant for the rearrangement of 2 to 11a in benzene
at 20 °C is 1.2 × 106 s-1 (see ref 21).
(10) Giese, B.; Beyrich-Graf, X.; Burger, J .; Kesselheim, C.; Senn,
M.; Schafer, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1742.
(11) Walling, C.; Cioffari, A. J . Am. Chem. Soc. 1972, 94, 6064.
(13) Brocks, J . J .; Beckhaus, H.-D.; Beckwith, A. L. J .; Ru¨chardt,
C. J . Org. Chem. 1998, 63, 1935.

Pathways for the Formation of Tetrahydrofurans
J . Org. Chem., Vol. 65, No. 2, 2000 525
Sch em e 8
corresponding p-methoxy-substituted system owing to the
instability of the diphenyl phosphate. However, we were
able to synthesize the regioisomer (10b) by the method
of Scheme 4; on photolysis in the presence of allyl alcohol
and tert-butyl thiol it provided only â,â-dimethyl-4-
methoxystyrene (19). Two further substrates (17d and
e) also led only to alkene formation on photolysis in the
presence of allyl alcohol and the thiol. Given the reason-
able expectation that 17d and 17e do provide the alkene
radical cation on fragmentation of the derived â-(phos-
phatoxy)alkyl radicals,7,8 it is clear that significant extra
stabilization of these radical cations, afforded by conjuga-
tion with a second aryl ring, enables other pathways to
compete with trapping by the alcohol nucleophile. This
observation is consistent with the report by J ohnston and
Schepp who noted that methanol addition to the styrene
radical cation is 6 × 103 times faster than to the more
stabilized p-methoxystyrene radical cation.14 Various
possibilites exist for the formation of 19 and 20a ,b from
the radical cations resulting from the fragmentation of
10b and 17d ,e, respectively. These include electron
transfer from the thiol or other donor; indeed, Giese has
proposed a similar pathway for the formation of alkene
from nucleoside-based radical cations.15 A second pos-
sibility is trapping by the thiol, to give a â-(alkylthio)-
alkyl radical, followed by elimination of the thiyl radical.
Yet a third possibility involves deprotonation to an allyl
radical followed by hydrogen transfer from the thiol. At
the present time we have not attempted to differentiate
between these alternatives.
The problem with realizing such a scheme lay in the
correct choice of precursor for the â-(phosphatoxy)alkyl
radical. Barton esters, as used in the intermolecular case,
did not seem like a wise choice as these active esters
might reasonably have been expected to condense with
the intramolecular alcohol resulting in the formation of
lactones.16 Similarly, â-bromoalkyl phosphates were dis-
counted owing to the evident complication of the bromide
being displaced by the nucleophile prior to the radical
step. The â-(arylselenyl)alkyl phosphates do not suffer
from this complication, but experience has taught us that
they are unstable with respect to epi-seleninium ion
formation and eventual elimination to the alkene. Ulti-
mately, we opted for the C-H bond as the ideal radical
precursor requiring no protecting group chemistry and
with generation of the â-(phosphatoxy)alkyl radical by
hydrogen atom abstraction by an alkoxyl radical (Scheme
8). The main question with this approach was the
potential for 1,6-hydrogen atom abstraction from the
benzylic position, rather than 1,5-abstraction to give the
desired â-(phosphatoxy)alkyl radical. Early studies on the
Barton reaction indicated that the 5-phenyl-1-pentyloxyl
radical did not abstract hydrogen from the benzylic site,
giving instead only products of 1,5-hydrogen abstrac-
tion.17 However, the influence of the additional C-H bond
weakening effect of the benzylic phosphate group in the
intended sequence remained an unknown that could only
be reliably probed by experiment. We selected the reac-
tion of triphenylstannane with N-alkoxyphthalimides,
recently described by the Kim group,18 as the means of
generating the alkoxyl radical such that eventual chain
propagation would be assured by the presence of the
stannane.
Sch em e 7
A series of three radical precursors with leaving groups
of different abilities was prepared uneventfully from
known 5-hydroxy-1-phenylpentanone,19 as outlined in
Scheme 9, via the common alcohol 27 using routine
techniques. Several methyl-substituted analogues (31-
36), for the most part as mixtures of diastereomers, were
obtained by variations on this theme as outlined in the
Supporting Information.
The cyclization reactions were conducted by dropwise
addition of triphenylstannane and AIBN, in benzene or
acetonitrile, to the substrate at reflux in the same solvent
followed by heating to reflux for a further 2 h and leading
We next turned our attention to intramolecular nu-
cleophilic attack on â-(phosphatoxy)alkyl radicals by
suitably disposed alcohols. As in the intermolecular case,
we anticipated two mechanistic pathways; one a Zipse-
like concerted displacement and the other stepwise and
dissociative with the intermediacy of a radical cation
(Scheme 7). We further anticipated that if the concerted
mechanism exists at all it is most likely to manifest itself
in such an intramolecular example where it, unlike the
dissociative pathway, benefits from the high effective
molarity.
(16) Barton esters have been formed in the presence of alcohols (for
some examples, see: Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413);
however, it was felt that lactonization would be a serious problem if
such a strategy were applied to the present system.
(14) J ohnston, L. J .; Schepp, N. P. J . Am. Chem. Soc. 1993, 115,
6564.
(15) Giese, B.; Burger, J .; Kang, T. W.; Kesselheim, C.; Wittmer, T.
J . Am. Chem. Soc. 1992, 114, 7322.
(17) Kabasakalian, P.; Townley, E. R.; Yudis, M. D. J . Am. Chem.
Soc. 1962, 84, 2716.
(18) Kim, S.; Lee, T. A.; Song, Y. Synlett. 1998, 501.
(19) Descotes, G.; Soula, J .-C. Bull. Soc. Chim. Fr. 1964, 2636.

526 J . Org. Chem., Vol. 65, No. 2, 2000
Crich et al.
Sch em e 9
Ta ble 2. Hyd r ogen Abstr a ction /Cycliza tion s
tetrahydro-
sub-
strate
furan
migration
(% yield)b
reduction
(% yield)b
solvent
benzene
benzene
benzene
benzene
benzene
benzene
benzene
(% yield)a
28
29
30
31
32
33
34
37 (95)
37 (60)
37 (0)
38 (90)
38 (85)
38 (0)
42 (25)
44 + 45 (74) 47 + 48 (26)
43 (15)
50 + 51 (35) 53 + 54 (65)
39 (90),
∼1/1
35
benzene
40 (92),
∼∼55/45
41 (0)
36
28
benzene
benzene/
56 + 57 (80) 59 + 60 (20)
44 + 45 (64) 47 + 48 (36)
37 (98)
∼acetonitrile 1/1
benzene/
∼acetonitrile 1/1
benzene/
∼acetonitrile 1/1
30
31
37 (0)
38 (92)
a
b
Yields of tetrahydrofurans refer to isolated materials. Yields
of migration and reduction products were determined by integra-
tion of the NMR spectra of the crude reaction mixtures.
to the results collected in Table 2. Several conclusions
are apparent from Table 2. First, any fears about the
regioselectivity of the hydrogen atom abstraction process
were misplaced. Second, the efficiency of the cyclization
reaction is a function of the leaving group with diphenyl
phosphate being optimal and acetate ineffective. Third,
a relatively inefficient cyclization of a diethyl phosphate
may be rescued by inclusion of a methyl group at the site
of nucleophilic attack. Fourth, little or no stereoselectivity
is observed under the present conditions.
Taken as a whole, the above series of observations
support very strongly the notion that vicinal nucleophilic
displacement of â-ester-substituted radicals occurs by a
dissociative mechanism involving initial fragmentation
of the radical to give a radical cation/ester anion pair with
subsequent capture by the nucleophile. The strongest
evidence for this mechanism is derived from the two
diethyl phosphates 29 and 32 from which it is seen that
additional substitution at the site of nucleophilic eventual
attack increases the yield, most likely through stabiliza-
tion of the intermediate radical cation. With less potent
leaving groups migration is a competing reaction as is
readily seen by the contrast between the diethyl and
diphenyl phosphates. This phenomenon is best attributed
to collapse of the radical cation/anion pair being competi-
tive with capture by the external nucleophile. In the case
of the acetates this collapse is much faster than nucleo-
philic attack and completely dominates the chemistry.
At this stage, however, we cannot completely rule out
the possibility that the acetate migration is taking place
through a concerted mechanism. From a practical point
of view, the acetate examples are complicated by an
intramolecular scrambling of the acetate group itself
between the two hydroxyls of the monoacetylated diol
products. This is evidently a post radical step and has
no bearing on the above discussion of mechanism; the
product mixtures may be simplified for analysis by simple
saponification.
In conclusion, it has been demonstrated that â-(phos-
phatoxy)alkyl radicals may be displaced by inter- or
intramolecular alcohols giving rise to â-(alkoxy)alkyl
radicals. These displacements may be engineered so as
to permit the formation of tetrahydrofurans. The majority
of evidence supports a dissociative mechanism involving
initial fragmentation of the â-(phosphatoxy)alkyl radical
to a radical cation/anion pair, even in the nonpolar
solvent benzene, which undergoes subsequent nucleo-
philic capture by the alcohol.
Exp er im en ta l Section
Gen er a l Meth od s.20 Compounds 121 and 7a -10a 8 were
prepared as previously described. Compounds prefixed by an
S are to be found in the Supporting Information.
(20) For general experimental details see ref 21.

Pathways for the Formation of Tetrahydrofurans
J . Org. Chem., Vol. 65, No. 2, 2000 527
Gen er a l P r otocol A. On e-P ot Ald ol Con d en sa tion /
P h osph or ylation . 2,4-Dim eth oxyben zyl 3-(Diph en ylph os-
p h a toxy)-3-m eth yl-2-(4-m eth oxyp h en yl)bu ta n oa te (8b).
LHMDS was prepared in situ by adding n-BuLi (1.70 mL, 4.25
mmol) to a solution of hexamethyldisilamine (1.08 mL, 4.68
mmol) in THF (8.0 mL) at -78 °C. After the mixture was
stirred for 20 min, 7b (0.893 g, 2.83 mmol) was added in THF
(2.0 mL). Dry acetone (0.31 mL, 4.25 mmol) was then added
at -78 °C over 30 min. After the mixture was stirred for 30
min, diphenyl chlorophosphate (1.14 g, 4.25 mmol) was added
in THF (2.0 mL). The reaction temperature was allowed to
warm slowly to -20 °C before the addition of saturated NH4-
Cl solution and EtOAc. The water layer was extracted with
EtOAc, and the combined organic phases were washed with
water and brine and then dried (Na2SO4). Removal of the
solvent under vacuum and flash chromatography on silica gel
(hexane/EtOAc 3/1) afforded 8b as an oil (0.79 g, 46%): 1H
NMR (CDCl3) δ 7.35-7.09 (m, 13 H), 6.38 (d, J ) 7.7 Hz, 2
H), 6.39-6.37 (m, 2 H), 5.05 (AB quart, J ) 33.0, 12.0 Hz, 2
H), 3.97 (s, 1 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 3.68 (s, 3 H), 1.70
(s, 3 H), 1.58 (s, 3 H); 13C NMR δ 171.1, 161.4, 159.4, 159.0,
150.8 (t), 131.4, 129.8, 129.7, 126.2, 125.2 (d), 120.4 (d), 116.5,
113.6, 104.1, 98.6, 87.8, 87.7, 62.4, 60.8, 60.7, 55.5, 55.4, 25.8,
25.4; 31P NMR δ -16.65. Anal. Calcd for C33H35O9P: C, 65.34;
H, 5.82. Found: C, 64.93; H, 5.72.
(d, J ) 11.5 Hz, 1 H), 3.10 (m, 1 H), 3.66 (t, J ) 9.0 Hz, 1 H),
4.19 (t, J ) 9.0 Hz, 1 H), 7.20-7.36 (m, 5 H); HRMS calcd for
C13H18O 190.1358, found 190.1360.
(1H)-2-Th ioxo-1-pyr idyl 3-Meth yl-2-ph en yl-2-bu ten oate
(14). This compound was obtained from 8a 8 by the exact
method used for the formation of 10a 8 with the exception that
the final purification/elimination was carried out by chroma-
tography on silica gel basified with Et3N: 1H NMR δ 7.61 (dd,
J ) 8.0, 1.8 Hz, 1 H), 7.40-7.31 (m, 6 H), 7.10 (m, 1 H), 6.53
(dt, J ) 6.9, 1.3 Hz, 1 H), 2.37 (s, 3 H), 1.78 (s, 3 H); 13C NMR
δ 138.0, 137.3, 136.2, 133.4, 130.4, 126.5, 127.9, 112.6, 25.2,
23.6. No further characterization was attempted on this
hydrolytically and photolytically unstable compound.
2,4-Dim et h oxyb en zyl 3-(d ip h en ylp h osp h a t oxy)-2,2-
d im eth yl-3-(4-ch lor op h en yl)p r op a n oa te (16a ) was pre-
pared from 2,4-dimethoxybenzyl 2-methylpropanoate21 and
4-chlorobenzaldehyde by general protocol A: 1H NMR δ 7.30-
7.11 (m, 13 H), 6.94 (d, J ) 8.3 Hz, 2 H), 6.44 (m, 2 H), 5.83
(d, J ) 8.2 Hz, 1 H), 4.99 (AB quart, J ) 54.6, 12.0 Hz, 2 H),
3.81 (s, 3 H), 3.77 (s, 3 H), 1.26 (s, 3 H), 1.07 (s, 3 H); 13C NMR
δ 174.6, 161.4, 159.1, 150.6 (t), 134.7, 134.4, 131.6, 129.9, 129.8,
129.3, 128.2, 125.5, 125.3, 120.3 (d), 120.0 (d), 116.5, 104.1,
98.6, 85.0, 84.9, 62.6, 55.5, 21.3, 20.5; 31P NMR δ -12.24. Anal.
Calcd for C32H32ClO8P: C, 62.90; H, 5.28. Found: C, 62.84;
H, 5.41.
Gen er a l P r otocol B. (1H)-2-Th ioxo-1-p yr id yl 3-(Dip h e-
n y lp h o s p h a t o x y )-3-m e t h y l-2-(4-m e t h o x y p h e n y l)b u -
ta n oa te (10b). A solution of 8b (0.264 g, 0.456 mmol) in
EtOAc (20 mL) was stirred under 1 atm of H2 over Pd/C (0.152
g, 50 wt %) overnight and then filtered. Removal of the solvent
under vacuum afforded 3-(diphenylphosphatoxy)-3-methyl-2-
(4-methoxyphenyl)butanoic acid, as an oil, quantitatively. No
further purification of this acid was attempted: 1H NMR
(CDCl3) δ 9.38 (br s, 1 H), 7.29-7.11 (m, 12 H), 6.79 (d, J )
8.8 Hz, 2 H), 3.96 (s, 1 H), 3.78 (s, 3 H), 1.69 (s, 3 H), 1.58 (s,
3 H); 13C NMR δ 175.8, 159.6, 150.7 (t), 131.4, 129.8, 129.4,
125.8, 125.3, 120.4, 120.3, 113.9, 87.8, 87.7, 60.6, 60.5, 55.4,
26.1, 25.2; 31P NMR δ -16.89. To a solution of this acid (0.17
g, 0.375 mmol) and 9 (0.103 g, 0.410 mmol) in CH2Cl2 (8.0 mL)
in a flask covered with aluminum foil was added n-Bu3P (0.091
mL, 0.573 mmol) at 0 °C under Ar. The reaction mixture was
stirred at room temperature for 3 h before aqueous Na2CO3
was added. The aqueous layer was extracted with CH2Cl2. The
combined organic phases were washed with water and brine,
dried (Na2SO4), and concentrated to dryness. Flash chroma-
tography on silica gel (within 10 min on a ca. 10 cm column,
hexane/EtOAc 2:1) in the dark gave 10b (0.161 g, 76%) as a
yellowish syrup: 1H NMR (CDCl3) δ 7.58 (dd, J ) 8.1, 1.6 Hz,
1 H), 7.33-7.07 (m, 13 H), 6.82 (d, J ) 8.8 Hz, 2 H), 6.43 (dt,
J ) 6.9, 1.8 Hz, 1 H), 4.35 (s, 1 H), 3.77 (s, 3 H), 1.77 (s, 3 H),
1.68 (s, 3 H); 13C NMR δ 175.5, 166.7, 159.8, 150.6 (q), 137.6,
137.2, 133.5, 131.3, 129.8, 125.4, 123.8, 120.3, 120.2, 120.1,
114.1, 112.6, 87.3 (d), 60.4, 58.0, 57.9, 55.3, 26.4, 25.2; 31P NMR
δ -16.63. No further characterization was attempted on this
hydrolytically and photolytically unstable compound.
Gen er a l P r otocol D. Con ver sion of 2,4-Dim eth oxyben -
zyl Ester s to Ba r ton Ester s via Oxid a tive Clea va ge w ith
CAN. (1H)-2-Th ioxo-1-p yr id yl 3-(Dip h en ylp h osp h a toxy)-
2,2-d im eth yl-3-(4-ch lor op h en yl)-p r op a n oa te (17a ). A so-
lution of 16a (0.803 g, 1.51 mmol) in a mixture of acetonitrile
and water (10:1 v/v, 26 mL) was treated with ceric ammonium
nitrate (1.59 g, 2.91 mmol), and the resulting mixture was
stirred at room temperature for 1 h. Water was then added
and the mixture extracted with EtOAc. The combined extracts
were concentrated to dryness, and the residue was taken up
in EtOAc, washed repeatedly with a freshly prepared 15%
aqueous solution of NaHSO3, water, and brine, and then dried
(Na2SO4). Removal of the solvent gave 3-(diphenylphosphatoxy)-
2,2-dimethyl-3-(4-chlorophenyl)propanoic acid as an oil quan-
titatively. Without further purification this acid was converted
to the title compound, exactly according to the method
described in general protocol B, in 57% yield: 1H NMR δ 7.79
(dd, 1 H), 7.60 (dd, 1 H), 7.30-7.10 (m, 12 H), 6.89 (d, 2 H),
6.38 (dt, 1 H), 5.95 (d, J ) 8.4 Hz, 1 H), 1.38 (s, 3 H), 1.37 (s,
3 H); 13C NMR δ 175.8, 170.2, 150.2 (t), 138.6, 137.1, 135.2,
133.8, 132.8, 130.0, 129.8, 129.4, 128.4, 125.9, 125.4, 120.4 (d),
119.7, 119.6, 112.7, 84.1, 84.0, 48.6, 48.5, 23.1, 17.6; 31P NMR
δ -11.79. Anal. Calcd for C28H25ClNO6PS‚0.5H2O: C, 58.08;
H, 4.52. Found: C, 57.93; H, 4.29.
cis/tr a n s-2,2,4-Tr im et h yl-3-(4-ch lor op h en yl)t et r a h y-
d r ofu r a n (18a ). Application of general protocol C to 17a gave
the title compound: 1H NMR δ trans 7.30 (d, J ) 8.5 Hz, 2
H), 7.14 (d, J ) 8.5 Hz, 2 H), 4.13 (t, J ) 8.0 Hz, 1 H), 3.48 (t,
J ) 8.4 Hz, 1 H), 2.75 (m, 1 H), 2.59 (d, J ) 11.5 Hz, 1 H),
1.29 (s, 3 H), 0.96 (d, J ) 8.1 Hz, 3 H), 0.84 (s, 3 H); cis 7.27
(d, J ) 8.5 Hz, 2 H), 7.06 (d, J ) 8.5 Hz, 2 H), 4.18 (t, J ) 8.9
Hz, 1 H), 3.59 (t, J ) 9.0 Hz, 1 H), 3.09 (m, 1 H), 2.88 (d, J )
7.7 Hz, 1 H), 1.35 (s, 3 H), 1.01 (s, 3 H), 0.67 (d, J ) 6.9 Hz, 3
H); 13C NMR δ 137.2, 135.8, 132.8, 131.6, 130.1, 128.7, 128.3,
127.8, 84.4, 83.4, 73.0, 72.6, 62.6, 58.4, 38.2, 37.5, 29.0, 28.4,
25.6, 24.4, 15.6, 14.4. Anal. Calcd for C13H17ClO: C, 69.48; H,
7.62. Found: C, 68.97; H, 7.71.
Gen er a l P r otocol C. P h otolysis of Ba r ton Ester s in th e
P r esen ce of ter t-Bu tylth iol a n d Allyl Alcoh ol. cis/tr a n s-
2,2,4-Tr im eth yl-3-p h en yltetr a h yd r ofu r a n (5). A solution
of 1 (0.107 g, 0.2 mmol) and tert-butylthiol (45.3 µL, 0.4 mmol)
in allyl alcohol (4.0 mL) in a Pyrex flask was photolyzed at
room temperature with a 250 W Philips’ Krypton lamp for 1
h. After removal of the volatiles under vacuun, 1H and 31P
NMR spectra indicated a clean reaction and complete conver-
sion of 1 with essentially quantitative formation of diphenyl
phosphate (31P NMR δ -10.36 in CDCl3). Purification by
preparative TLC (hexane/EtOAc 20:1) gave 5 (32 mg, 82%) as
4-Meth oxy-â,â-d im eth ylstyr en e (19).22 Application of
general protocol C to 10b gave the title compound: 1H NMR
δ 7.16 (d, J ) 8.7 Hz, 2 H), 6.86 (d, J ) 8.7 Hz, 2 H), 6.21 (s,
1 H), 3.81 (s, 3 H), 1.89 (d, J ) 1.1 Hz, 3 H), 1.85 (d, J ) 1.0
Hz, 3 H).
â-4-Meth oxyp h en yl-â-m eth ylstyr en e (20a ).23 Application
of general protocol C to 17d gave the title compound: 1H NMR
δ 7.48 (d, J ) 8.5 Hz, 2 H), 7.26-7.05 (m, 5 H), 6.90 (d, J )
8.5 Hz, 2 H), 3.82 (s, 3 H), 2.28 (d, J ) 1.1 Hz, 3 H).
1
the major product. tr a n s-5: H NMR (CDCl3) δ 0.85 (s, 3 H),
0.97 (d, J ) 6.4 Hz, 3 H), 1.31 (s, 3 H), 2.62 (d, J ) 11.5 Hz,
1 H), 2.79 (m, 1 H), 3.50 (dd, J ) 9.3, 8.0 Hz, 1 H), 4.14 (t, J
) 8.0 Hz, 1 H), 7.20-7.36 (m, 5 H); 13C NMR (CDCl3) δ 15.7,
24.5, 28.5, 38.0, 63.2, 72.7, 83.9, 127.0, 128.5, 128.9, 139.0. cis-
5: δ 0.68 (d, J ) 7.0 Hz, 3 H), 1.02 (s, 3 H), 1.36 (s, 3 H), 2.92
(21) Choi, S.-Y.; Crich, D.; Horner, J . H.; Huang, X.; Newcomb, M.;
Whitted, P. O. Tetrahedron 1999, 55, 3317.
(22) Rappoport, I.; Gal, A. J . Chem. Soc., Perkin Trans. 2 1973, 301.
(23) Gupton, J . T.; Layman, W. J . J . Org. Chem. 1987, 52, 3683.

528 J . Org. Chem., Vol. 65, No. 2, 2000
Crich et al.
r-Meth ylstilben e (20b).24 Application of general protocol
C to 17e gave the title compound: 1H NMR δ 7.55-7.26 (m,
10 H), 6.85 (s, 1 H), 2.29 (d, J ) 1.3 Hz, 3 H).
H), 3.93 (m, 1 H), 3.80 (m, 2 H), 2.10-1.65 (m), 1.52 (m), 1.34
(m) (5 H), 1.20 (dt, J ) 7.0, 0.8 Hz), 1.09 (dt, J ) 6.9, 0.9 Hz)
(3 H), 1.00 (d, J ) 6.7 Hz), 0.79 (d, J ) 6.8 Hz) (3 H); 13C NMR
δ 163.7, 139.6, 139.4, 134.6, 129.1, 128.3, 128.1, 127.3, 127.1,
123.6, 84.6 (d), 84.3 (d), 78.8, 78.6, 63.7 (t), 39.8 (d), 39.6 (d),
28.5, 28.2, 25.9, 25.7, 16.1 (d), 15.3, 14.9; 31P NMR δ -0.86,
-1.02. Anal. Calcd for C24H30NO7P: C, 60.06; H, 6.40. Found:
C, 59.91; H, 6.42.
Gen er a l P r otocol E. P h osp h or yla tion . 1-(Dieth ylp h os-
p h a toxy)-1-p h en yl-5-(N-p h th a lim id oxy)p en ta n e (29). Di-
ethyl chlorophosphate (0.112 g, 0.651 mmol) in CH2Cl2 (1.0
mL) was added at room temperature to a solution of 27 (0.141
g, 0.434 mmol) and DMAP (0.08 g, 0.651 mmol) in CH2Cl2 (8.0
mL). The resulting reaction mixture was stirred at room
temperature for 24 h before it was diluted with EtOAc. The
organic layer was washed with saturated NH4Cl solution,
water, and brine, dried (Na2SO4), and concentrated to dryness.
Column chromatography on silica gel eluting with hexane/
EtOAc (1/1) gave 29 (0.104 g, 52%, 100% based on recovered
27) as a colorless oil: 1H NMR δ 7.80 (dd, 2 H), 7.73 (dd, 2 H),
7.37-7.26 (m, 5 H), 5.27 (dd, J ) 13.7, 7.3 Hz, 1 H), 4.14 (t, J
) 6.6 Hz, 2 H), 4.08 (m, 1 H), 3.96 (m, 1 H), 3.85 (m, 2 H),
2.03 (m, 1 H), 1.89 (m, 1 H), 1.79 (m, 2 H), 1.62 (m, 1 H), 1.47
(m, 1 H), 1.22 (dt, J ) 7.1, 0.8 Hz, 3 H), 1.11 (dt, J ) 7.1, 0.8
Hz, 3 H); 13C NMR δ 163.7, 140.6, 134.6, 132.3, 132.2, 129.1,
128.6, 128.4, 126.6, 123.6, 80.5 (d), 78.3, 63.7 (t), 37.7 (d), 27.9,
21.6, 16.1 (t); 31P NMR δ -1.08. Anal. Calcd for C23H28NO7P‚
1/4H2O: C, 59.29; H, 6.16. Found: C, 59.02; H, 6.08.
1-(Acet oxy)-2-m et h yl-1-p h en yl-5-(N-p h t h a lim id oxy)-
p en ta n e (33). Acetylation of S5 gave 33 quantitatively: 1H
NMR δ 7.82 (m, 2 H), 7.73 (m, 2 H), 7.31-7.23 (m, 5 H), 5.64
(d, J ) 6.3 Hz), 5.53 (d, J ) 7.7 Hz) (1 H), 4.18 (t, J ) 6.4 Hz),
4.11 (t, J ) 6.6 Hz) (2 H), 2.09 (s), 2.07 (s) (3 H), 2.04 (m),
1.95-1.66 (m), 1.59-1.18 (m) (5 H), 0.95 (d, J ) 6.7 Hz), 0.80
(d, J ) 6.8 Hz) (3 H); 13C NMR δ 170.5, 163.8, 139.6, 134.6,
129.1, 128.4, 127.9, 127.8, 127.2, 126.9, 123.6, 80.0, 79.3, 78.7,
78.6, 38.4, 38.2, 28.8, 28.4, 25.9, 21.3, 15.7, 15.0. Anal. Calcd
for C22H23NO5: C, 69.28; H, 6.08. Found: C, 69.13; H, 6.04.
3-Meth yl-1-p h en yl-1-(d ip h en ylp h osp h a toxy)-5-(N-p h -
th a lim id oxy)p en ta n e (34). Phosphorylation of S14 with
diphenyl chlorophosphate according to general protocol E gave
34 in 91% yield: 1H NMR δ 7.82 (m, 2 H), 7.74 (m, 2 H), 7.36-
7.15 (m, 13 H), 5.60 (m, 1 H), 4.14 (m, 2 H), 2.17 (m), 1.95 (m),
1.81 (m) (3 H), 1.65 (m, 2 H), 0.98 (d, J ) 5.4 Hz, 3 H); 13C
NMR δ 163.7, 150.7 (t), 140.2, 139.3, 134.6, 129.8, 129.7, 129.1
(d), 128.7 (d), 127.1, 126.8, 125.3, 125.1, 123.6, 120.3, 120.2,
120.1, 81.5, 81.4, 80.9, 80.8, 76.8, 76.6, 45.5, 45.4, 44.5, 44.4,
35.3, 34.8, 26.7, 26.5, 19.6, 19.0; 31P NMR δ -11.82, -12.00.
Anal. Calcd for C32H30NO7P: C, 67.24; H, 5.29. Found: C,
67.66; H, 5.70.
1-P h en yl-1-(d ip h en ylp h osp h a t oxy)-5-(N-p h t h a lim id -
oxy)p en ta n e (28). This compound was prepared by general
protocol E, with replacement of diethyl chlorophosphate by
diphenyl chlorophosphate, in 63% yield: 1H NMR δ 7.81 (dd,
2 H), 7.72 (dd, 2 H), 7.33-7.06 (m, 13 H), 6.97 (dd, 2 H), 5.54
(dd, J ) 13.5, 7.3 Hz, 1 H), 4.09 (t, J ) 6.6 Hz, 2 H), 2.08 (m,
1 H), 1.95 (m, 1 H), 1.74 (m, 2 H), 1.47 (m, 2 H); 13C NMR δ
163.7, 150.7 (t), 139.6, 134.6, 129.8, 129.7, 129.1, 128.6, 126.7,
125.4, 125.2, 123.6, 120.4, 120.3, 120.2, 120.1, 82.6 (d), 78.1,
4-Meth yl-1-p h en yl-1-(d ip h en ylp h osp h a toxy)-5-(N-p h -
th a lim id oxy)p en ta n e (35). Phosphorylation of S23 with
diphenyl chlorophosphate according to general protocol E gave
35 97% yield: 1H NMR δ 7.80 (m, 2 H), 7.72 (m, 2 H), 7.35-
7.05 (13 H), 6.97 (d, 2 H), 5.52 (dd, J ) 13.1, 5.8 Hz, 1 H), 3.96
(ddd, J ) 10.0, 7.7, 1.5 Hz, 1 H), 3.88 (t, J ) 7.7 Hz, 1 H),
2.18-1.88 (m, 3 H), 1.61-1.40 (m, 1 H), 1.35-1.12 (m, 1 H),
1.00 (dd, J ) 6.7, 2.1 Hz, 3 H); 13C NMR δ 163.6, 150.8, 150.7,
150.6, 139.6, 134.6, 129.8, 129.7, 129.1, 128.6, 126.7, 125.4,
125.2, 123.6, 120.4, 120.3, 120.2, 83.2, 35.1 (q), 32.3 (d), 28.8,
28.7, 16.8. Anal. Calcd for C32H30NO7P1/2H2O: C, 66.20; H,
5.38. Found: C, 66.36; H, 5.22.
37.4 (d), 27.8, 21.4; 31P NMR δ -11.89. Anal. Calcd for C31H28
NO7P: C, 66.78; H, 5.06. Found: C, 66.64; H, 5.08.
-
1-(Acetoxy)-1-ph en yl-5-(N-ph th alim idoxy)pen tan e (30).
4-(1-Pyrrolidinyl)pyridine (0.16 g, 1.07 mmol) was added at
room temperature to a solution of 27 (0.692 g, 2.13 mmol) and
Ac2O (0.613 mL, 8.52 mmol) in NEt3 (15.0 mL). The resulting
reaction mixture was stirred at room temperature overnight
before it was diluted with EtOAc and saturated NH4Cl
solution. The organic layer was washed with 2 N HCl to pH
6-7, washed subsequently with water, saturated NaHCO3
solution, water, and brine, dried (Na2SO4), and concentrated
to dryness. Column chromatography on silica gel (hexane/
EtOAc 1/1) gave 30 (0.704 g, 90%) as a white solid: mp 92-
94 °C; 1H NMR δ 7.83 (dd, 2 H), 7.73 (dd, 2 H), 7.34-7.26 (m,
5 H), 5.75 (dd, J ) 7.6, 6.1 Hz, 1 H), 4.17 (t, J ) 6.6 Hz, 2 H),
2.08 (s, 3 H), 2.00 (m, 1 H), 1.90-1.76 (m, 3 H), 1.54 (m, 2 H);
13C NMR δ 170.6, 163.8, 140.7, 134.6, 129.1, 128.6, 128.1,
126.7, 123.7, 78.3, 76.0, 36.1, 28.0, 21.8, 21.5. Anal. Calcd for
Gen er a l P r ot ocol F . Mit su n obu R ea ct ion for t h e
In tr od u ction of th e P h th a lim id oxy Gr ou p . 1-(Acetoxy)-
1-m eth yl-1-p h en yl-5-(N-p h th a lim id oxy)p en ta n e (36). Di-
ethyl azodicarboxylate (0.128 mL, 0.794 mmol) was added
dropwise at room temperature to a solution of 59 (0.104 g, 0.44
mmol), N-hydroxyphthalimide (0.102 g, 0.66 mmol), and PPh3
(0.177 g, 0.66 mmol) in THF (7.0 mL). The resulting reaction
mixture was stirred at room temperature for 24 h before it
was diluted with EtOAc and water. The aqueous layer was
further extracted with EtOAc, and the combined organic
phases were washed with saturated aqueous NaHCO3, water,
and brine, dried (Na2SO4), and concentrated to dryness.
Column chromatography on silica gel (hexane/EtOAc 1/1) gave
36 (88 mg, 52%) as a white solid: mp 119-121 °C; 1H NMR δ
7.82 (dd, 2 H), 7.74 (dd, 2 H), 7.32-7.19 (m, 5 H), 4.14 (t, J )
6.6 Hz, 2 H), 2.07 (s, 3 H), 2.04 (m, 2 H), 1.85 (s, 3 H), 1.74 (m,
2 H), 1.41 (m, 2 H); 13C NMR δ 169.9, 163.8, 145.1, 134.6, 129.1,
128.4, 127.0, 124.7, 123.7, 84.0, 78.4, 42.3, 28.4, 25.0, 22.5, 20.1.
Anal. Calcd for C22H23NO5‚1/4H2O: C, 68.47; H, 6.14. Found:
C, 68.68; H, 6.10.
C
21H21NO5: C, 68.65; H, 5.76. Found: C, 68.75; H, 5.80.
2-Meth yl-1-p h en yl-1-(d ip h en ylp h osp h a toxy)-5-(N-p h -
th a lim id oxy)p en ta n e (31). Phosphorylation of S5 with
diphenyl chlorophosphate according to general protocol E gave
31 in 77% yield: 1H NMR δ 7.82-7.79 (m, 2 H), 7.74-7.71
(m, 2 H), 7.32-7.07 (m, 13 H), 6.93 (m, 2 H), 5.40 (dd, J ) 7.8,
6.2 Hz), 5.28 (t, J ) 7.5 Hz) (1 H), 4.05 (m, 2 H), 2.06 (m, 1 H),
1.88-1.63 (m, 2 H), 1.48 (m), 1.26 (m) (2 H), 0.96 (d, J ) 6.7
Hz), 0.77 (d, J ) 6.8 Hz) (3 H); 13C NMR δ 163.8, 150.8, 150.7,
150.6, 138.5, 138.3, 134.6, 129.8, 129.7, 129.0 (d), 128.5, 128.4,
127.4, 127.1, 125.3, 125.2, 123.6, 120.4, 120.3, 120.2, 120.1,
86.7, 86.6, 86.3, 86.2, 78.6, 78.5, 39.8, 39.7, 39.5, 39.4, 28.3,
28.1, 25.8, 25.6, 15.2, 14.8; 31P NMR δ -11.65, -11.83. Anal.
Calcd for C32H30NO7P‚1/4H2O: C, 66.72; H, 5.34. Found: C,
66.71; H, 5.33.
1-(Diet h ylp h osp h a t oxy)-2-m et h yl-1-p h en yl-5-(N-p h -
th a lim id oxy)p en ta n e (32). Phosphorylation of S5 with di-
ethyl chlorophosphate according to general protocol E gave 32
in 60% yield: 1H NMR δ 7.81 (m, 2 H), 7.72 (m, 2 H), 7.32-
7.22 (m, 5 H), 5.12 (dd, J ) 8.0, 6.2 Hz), 5.03 (t, J ) 7.6 Hz) (1
H), 4.18 (t, J ) 6.5 Hz), 4.11 (t, J ) 6.6 Hz) (2 H), 4.09 (m, 1
Gen er a l P r otocol G. Hyd r ogen Abstr a ction /Cycliza -
tion . A solution of Ph3SnH (1.3 equiv) and AIBN (50 mol %)
in degassed benzene (0.002 M in Ph3SnH) or in degassed CH3-
CN and PhH (v/v 1/1) (0.002 M in Ph3SnH) was added with a
syringe pump (0.49 mL/h) under Ar to a refluxing solution of
the phosphate in degassed benzene (0.001 M in phosphate).
Stirring was continued for another 2 h after the addition
finished before the solvent was removed under vacuum. In
each case the crude reaction mixture was inspected by 1H NMR
spectroscopy before it was subjected to preparative TLC
(hexane/EtOAc 10/1) to afford the product.
(24) Kawashima, T.; Ishii, T.; Inamoto, N. Bull. Chem. Soc. J pn.
1987, 60, 1831.

Pathways for the Formation of Tetrahydrofurans
J . Org. Chem., Vol. 65, No. 2, 2000 529
2-Ben zyltetr a h yd r ofu r a n (37):25 95% from 28 and 60%
from 29; 1H NMR δ 7.34-7.22 (m, 5 H), 4.09 (m, 1 H), 3.91 (q,
J ) 8.0 Hz, 1 H), 3.77 (dt, J ) 8.0, 6.5 Hz, 1 H), 2.95 (dd, J )
13.6, 6.4 Hz, 1 H), 2.77 (dd, J ) 13.6, 6.5 Hz, 1 H), 1.88 (m, 3
H), 1.58 (m, 1 H); 13C NMR δ 139.1, 129.4, 128.4, 126.3, 80.2,
68.0, 42.1, 31.1, 25.7.
cis/tr a n s-2-Ben zyl-4-m eth yltetr a h yd r ofu r a n (40): 92%;
1H NMR δ 7.24 (m, 5 H), 4.21 (m), 4.10 (m) (1 H), 4.02 (dd, J
) 8.2, 6.9 Hz), 3.90 (t, J ) 7.8 Hz) (1 H), 3.38 (t, J ) 8.0 Hz),
3.28 (dd, J ) 8.2, 7.0 Hz) (1 H), 3.00 (dd, J ) 9.9, 4.8 Hz), 2.94
(dd, J ) 10.2, 4.8 Hz) (1 H), 2.80 (dd, J ) 10.2, 5.1 Hz), 2.74
(dd, J ) 9.9, 4.8 Hz) (1 H), 2.30 (m), 2.08 (m) (1 H), 1.81 (m),
1.54 (m) (1 H), 1.26-1.10 (m, 1 H), 1.03 (d, J ) 6.6 Hz), 1.00
(d, J ) 6.8 Hz) (3 H); 13C NMR δ 139.2, 129.4 (d), 128.5, 126.3,
81.0, 79.7, 75.3, 74.8, 42.5, 40.8, 39.3, 34.5, 33.3, 18.2, 18.0.
Anal. Calcd for C12H16O: C, 81.77; H, 9.15. Found: C, 82.04;
H, 9.19.
2-Ben zyl-2-m eth yltetr a h yd r ofu r a n (38):26 90% from 31
1
and 85% from 32: H NMR δ 7.31-7.21 (m, 5 H), 3.85 (m, 1
H), 3.79 (m, 1 H), 2.80 (s, 2 H), 1.97-1.60 (m, 4 H), 1.19 (s, 3
H); 13C NMR δ 138.6, 130.5, 128.0, 126.2, 82.9, 67.5, 47.0, 36.3,
26.5, 26.1.
cis/tr a n s-2-Ben zyl-3-m eth yltetr a h yd r ofu r a n (39): 90%;
1H NMR δ 7.27 (m, 5 H), 4.04 (dt, J ) 8.1, 5.5 Hz), 3.97 (dt, J
) 14.7, 8.0 Hz) (1 H), 3.83 (m), 3.74 (ddd, J ) 14.1, 8.5, 5.6
Hz), 3.59 (dt, J ) 7.3, 5.0 Hz) (2 H), 2.90-2.70 (m, 2 H), 2.27
(m), 2.08 (m), 1.89 (m), 1.67-1.47 (m) (3 H), 1.03 (d, J ) 7.0
Hz), 0.97 (d, J ) 6.5 Hz), (3 H); 13C NMR δ 139.9, 139.3, 129.5,
129.2, 128.5 (d), 126.3, 126.2, 86.5, 82.5, 67.0, 66.4, 40.7, 38.8,
37.1, 35.7, 34.8, 34.1, 17.5, 14.7. Anal. Calcd for C12H16O: C,
81.77; H, 9.15. Found: C, 81.52; H, 9.23.
Ack n ow led gm en t. We thank the NSF (Grants CHE
9625256 and CHE 9614968) for support to D.C. and
M.N., respectively, and the University of Illinois at
Chicago for a University Fellowship (X.H.).
Su p p or tin g In for m a tion Ava ila ble: Experimental parts
and characterization data for all substrates, their precursors,
and all minor products not included in the above Experimental
Section. This material is available free of charge via the
Internet at http://pubs.acs.org.
(25) Senda, Y.; Kanto, H.; Itoh, H. J . Chem. Soc., Perkin Trans. 2
1997, 1143.
(26) Combret, J .-C.; Larcheveque, M.; Leroux, Y. Bull. Soc. Chim.
Fr. 1971, 3501.
J O991570O