The reaction of α-diazo-β-hydroxy esters with boron trifluoride etherate: Generation and rearrangement of destabilized vinyl cations. A detailed experimental and theoretical study

Article abstract of DOI:10.1021/ja950971s

Cyclic ethyl 2-diazo-3-hydroxy carboxylates were prepared by treating ethyl diazoacetate with LDA followed by reaction with a series of cyclic ketones. Further treatment of these α-diazo-β-hydroxy esters with boron trifluoride etherate in various solvents affords an unusual array of products. Product types and ratios were found to be strongly dependent on ring size and the solvent used. The reaction proceeds by Lewis acid complexation of the alcohol functionality of the diazo hydroxy ester with BF₃ etherate followed by neighboring-group participation of the diazo moiety to generate a cycloalkylidene diazonium salt. Loss of nitrogen produces a highly reactive, destabilized, linear vinyl cation. Ring expansion via a 1,2-methylene shift leads to the formation of a more stable, bent cycloalkenyl vinyl cation. A subsequent 1,2-methylene shift results in ring contraction ultimately leading to a stable allylic cation. This cation is either trapped by the solvent or else undergoes cyclization with the adjacent ester group to give a lactone. Computational studies at the 6-31G* level were performed to determine the geometry of the optimized vinyl cations. Relative energies suggest a moderate energy gain for isomerization of the initial vinyl cation V₁ to the rearranged vinyl cation V₂ followed by a large stabilization in energy for subsequent conversion to the allyl cation A₁. Compared with isolated product distributions, the energy profiles suggest kinetically-controlled V₁ → V₂ → A₁ migrations. Finally, the calculations suggest that in diethyl ether the carbocations may be coordinated to a molecule of solvent resulting in "protected" cationic intermediates with nonlinear geometries.

Full text of DOI:10.1021/ja950971s

VOLUME 118, NUMBER 1
J ANUARY 10, 1996
© Copyright 1996 by the
American Chemical Society
The Reaction of R-Diazo-â-hydroxy Esters with Boron
Trifluoride Etherate: Generation and Rearrangement of
Destabilized Vinyl Cations. A Detailed Experimental and
Theoretical Study
Roberto Pellicciari,*,† Benedetto Natalini,† Bahman M. Sadeghpour,†
,|
Maura Marinozzi,† James P. Snyder,*,‡ Bobby L. Williamson,
Jeffrey T. Kuethe,| and Albert Padwa*,|
Contribution from the Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, UniVersita` degli
Studi, Perugia, Italy, Istituto di Ricerche di Biologia Molecolare P. Angeletti, Rome, Italy, and
Department of Chemistry, Emory UniVersity, Atlanta, Georgia 30322
ReceiVed March 24, 1995. ReVised Manuscript ReceiVed July 5, 1995X
Abstract: Cyclic ethyl 2-diazo-3-hydroxy carboxylates were prepared by treating ethyl diazoacetate with LDA followed
by reaction with a series of cyclic ketones. Further treatment of these R-diazo-â-hydroxy esters with boron trifluoride
etherate in various solvents affords an unusual array of products. Product types and ratios were found to be strongly
dependent on ring size and the solvent used. The reaction proceeds by Lewis acid complexation of the alcohol
functionality of the diazo hydroxy ester with BF3 etherate followed by neighboring-group participation of the diazo
moiety to generate a cycloalkylidene diazonium salt. Loss of nitrogen produces a highly reactive, destabilized,
linear vinyl cation. Ring expansion Via a 1,2-methylene shift leads to the formation of a more stable, bent cycloalkenyl
vinyl cation. A subsequent 1,2-methylene shift results in ring contraction ultimately leading to a stable allylic cation.
This cation is either trapped by the solvent or else undergoes cyclization with the adjacent ester group to give a
lactone. Computational studies at the 6-31G* level were performed to determine the geometry of the optimized
vinyl cations. Relative energies suggest a moderate energy gain for isomerization of the initial vinyl cation V1 to
the rearranged vinyl cation V2 followed by a large stabilization in energy for subsequent conversion to the allyl
cation A1. Compared with isolated product distributions, the energy profiles suggest kinetically-controlled V1 f V2
f A1 migrations. Finally, the calculations suggest that in diethyl ether the carbocations may be coordinated to a
molecule of solvent resulting in “protected” cationic intermediates with nonlinear geometries.
Introduction
since the turn of this century.1-8 The major methods used for
the generation of vinyl cations consist of (1) electrophilic
addition to the triple bond of acetylenes9 or the cumulene bond
of allenes,10 (2) intramolecular participation of acetylenic11 and
allenyl12 bonds in solvolysis reactions, and (3) ionization of
suitable vinylic derivatives.2j,5,13 Less frequently employed
methods include deamination,14 fragmentation,15 photolysis,16
The chemistry of carbenium ions has been extensively studied
† Istituto di Chimica Farmaceutica e Tecnica Farmaceutica.
‡ Current address: Cherry L. Emerson Center, Department of Chemistry,
Emory University, Atlanta, GA 30329.
§ Istituto di Ricerche di Biologia Molecolare P. Angeletti.
NIH Postdoctoral Research Fellow, 1995.
| Emory University.
(1) Nenitzescu, C. D. In Carbonium Ions; Olah, G. A., Schleyer, P. v.
R., Eds.; Wiley-Interscience: New York, 1968; Vol. 1, pp 1-75.
X Abstract published in AdVance ACS Abstracts, November 15, 1995.
0002-7863/96/1518-0001$12.00/0 © 1996 American Chemical Society

2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
oxidative decarboxylation,17 electrooxidation,18 mass spectrom-
in solvolysis reactions, electron-donating neighboring groups
such as phenyl, vinyl, allyl, or cyclopropyl are necessary.
etry,19 and â-decay of a covalently-bonded tritium atom.20
A
necessary requirement for the direct solvolytic generation of
vinyl cations is either the use of leaving groups of high
nucleofugality, such as the trifluoromethanesulfonate (triflate)
anion21,22 or nonafluorobutanesulfonate (nonaflate) anion,22,23
or the presence of stabilizing neighboring groups in the
molecule.2f,2g If halide or tosylate leaving groups are employed
The solvolysis of cyclic vinyl substrates is of special interest
because it can lead to a cyclic vinyl cation intermediate. The
amount of strain inherent in the cyclic vinyl cation is a function
of the ring size. Early studies in this area demonstrated the
difficulty of forming vinyl cations with relatively small rings.24
This difficulty was ascribed to the high energy of the transition
state leading to the bent vinyl cation since larger, more flexible
rings solvolyze at rates similar to or higher than those observed
for the related acyclic E-2-butenyl sulfonates.25 This observation
suggests that vinyl cations prefer to adopt a linear geometry.
Saturated carbocations where an electronegative substituent is
attached directly to the carbon atom bearing the positive charge
have been extensively studied.26 In contrast, examples of
“destablized” vinyl cations are rare but have been implicated
as intermediates in the synthesis of â-functionalized alkynyl-
(phenyl)iodonium salts.27 Likewise, the photolysis of R-formyl
and R-cyano vinyl halides affords products derived from the
corresponding electronegatively-substituted vinyl cations.28
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Nefedov, V. D.; Sinotova, E. N.; Lebedev, V. P. Russ. Chem. ReV. 1992,
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A. A.; Kanishchev, M. I. Russ. Chem. ReV. 1981, 50, 553. (d) Stang, P. J.;
Rappoport, Z.; Hanack, M.; Subramanian, L. B. Vinyl Cations; Academic
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Hanack, M. Angew. Chem., Int. Ed. Engl. 1978, 17, 333. (g) Hanack, M.
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The sp-hybridized carbon atom of a vinyl cation possesses
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pairs of electrons, multiple bonds, and σ-bonds react rapidly
with these reactive intermediates. For example, the solvolysis
of vinyl derivatives in oxygen-containing solvents typically
affords vinyl ethers and ketones as products which is the
consequence of deprotonation of an intermediate oxonium ion.29
Vinyl cations can also undergo reactions with the electrons of
C-H and C-C σ-bonds. The deprotonation and rearrangement
of vinyl cations to produce alkynes are examples of such σ-bond
reactions. Rearrangement of these unsaturated cations can be
classified into two general categories: (1) migration to the
double bond with the formation of an allylic cation (1 f 2)
and (2) migration of an alkyl group across the double bond
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is formed from a less stable progenitor.
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Reaction of R-Diazo-â-hydroxy Esters with BF3‚OEt2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996 3
moiety, which is crucial in the conversion of 6a to 9, is missing
with this set of compounds.
of R-diazo-â-hydroxycarbonyl compounds 6a,b.30-32 Earlier
work in our groups as well as others have shown that these
diazo compounds are valuable synthetic intermediates which
undergo a wide range of transformations.33-47 Notably, a recent
study demonstrated that the reaction of R-diazo-â-hydroxy esters
of type 6b with BF3‚OEt2 in various solvents affords an unusual
array of products.48 Since the mechanism associated with this
process seemingly involves a vinyl cation intermediate, we
decided to carry out a more in-depth investigation of the reaction
of various R-diazo-â-hydroxy esters with BF3‚OEt2 in order to
gain a better understanding of the reaction pathway. Herein
we detail the results of such a study.
Cyclohexyl Derivatives. Our initial endeavors focused on
the chemistry of the R-diazo ester 10 derived by treating
cyclohexanone with ethyl lithiodiazoacetate. The outcome of
the reaction of 10 with BF3‚OEt2 in various solvents clearly
indicates that the process is greatly influenced by the manner
in which the reaction is performed. Thus, exposure of 10 to
BF3‚OEt2 in pentane resulted in the isolation of lactone 11 in
75% yield. Treatment of 10 in benzene provided 12 in 74%
isolated yield along with minor amounts of lactone 11 as well
Results
The reaction of acyclic compounds of type 6a (R2 ) H) with
BF3‚OEt2 in a polar solvent such as acetonitrile results in the
formation of the corresponding acylacetylene 9 as the major
product together with minor amounts of migration prod-
ucts.31,38,43,44 The formation of 9 has been rationalized as
proceeding Via coordination of the diazoester with BF3‚OEt2
followed by generation of the alkenyldiazonium salt 8. Depro-
tonation of 8 with extrusion of molecular nitrogen affords alkyne
9. The reaction of BF3‚OEt2 with R-diazo-â-hydroxycarbonyl
compounds derived from ketonic substrates 6b became of
interest to us, since the hydrogen atom located R to the diazo
(30) Scho¨llkopf, U.; Frasnelli, H. Angew. Chem., Int. Ed. Engl. 1970, 9,
301.
(31) Wenkert, E.; McPherson, C. A. J. Am. Chem. Soc. 1972, 94, 8084.
(32) Scho¨llkopf, U.; Ba´nhidai, B.; Frasnelli, H.; Meyer, R.; Beckhaus,
H. Liebigs Ann. Chem. 1974, 1767.
(33) Ye, T.; McKervey, M. A. Tetrahedron 1992, 48, 8007.
(34) Padwa, A.; Kulkarni, Y. S.; Zhang, A. J. Org. Chem. 1990, 55,
4144.
(35) Singh, A. K.; Bakshi, R. K.; Corey, E. J. J. Am. Chem. Soc. 1987,
109, 6187.
(36) Pellicciari, R.; Natalini, B.; Cecchetti, S.; Fringuelli, R. J. Chem.
Soc., Perkin Trans. 1 1985, 493.
(37) Nagao, K.; Chiba, M.; Kim, S.-W. Synthesis 1983, 197.
(38) Miyauchi, K.; Hori, K.; Hirai, T.; Takebayashi, M.; Ibata, T. Bull.
Chem. Soc. Jpn. 1981, 54, 2142.
(39) Ikota, N.; Takamura, N.; Young, S. D.; Ganem, B. Tetrahedron
Lett. 1981, 22, 4163.
(40) Pellicciari, R.; Fringuelli, R.; Sisani, E.; Curini, M. J. Chem. Soc.,
Perkin Trans. 1 1981, 2566.
as 2-fluoroalkenoate 13. The structure of 12 was confirmed
by converting it into the previously reported cis-2-benzylcy-
clohexanecarboxylic acid.49 Likewise, stirring a sample of 10
with BF3‚OEt2 in p-xylene afforded 14 in 47% isolated yield.
Finally, the reaction of 10 with BF3‚OEt2 in acetonitrile resulted
in the formation of 2-(acetamidomethyl)-1-cyclohexene car-
boxylate (15) as well as lactone 11 in 38% and 23% isolated
yields, respectively. In this case, minor amounts of 16 and diene
17 were also obtained.
The possibility that these products are all derived from a
common vinylogous R-diazo ester intermediate such as 20 was
considered. Such an intermediate could conceivably be obtained
by the dehydration of 10 followed by a precedented rearrange-
ment of the initially-formed â,γ-unsaturated-R-diazo ester (18)
to pyrazole 19. Subsequent rearrangement of 19 under the
reaction conditions could ultimately afford 20. To test this
hypothesis, R-diazo-â-hydroxy ester 10 was dehydrated using
phosphorus oxychloride/pyridine to give vinyl diazo ester 18.
(41) Pellicciari, R.; Sisani, E.; Fringuelli, R. Tetrahedron Lett. 1980, 21,
4039.
(42) Pellicciari, R.; Fringuelli, R.; Ceccherelli, P.; Sisani, E. J. Chem.
Soc., Chem. Commun. 1979, 959.
(43) Pellicciari, R.; Castagnino, E.; Fringuelli, R.; Corsano, S. Tetrahe-
dron Lett. 1979, 481.
(44) Pellicciari, R.; Castagnino, E.; Corsano, S. J. Chem. Res. (S) 1979,
76.
(45) Wenkert, E.; Ceccherelli, P.; Fugiel, R. A. J. Org. Chem. 1978, 43,
3982.
(46) Pellicciari, R.; Natalini, B. J. Chem. Soc., Perkin Trans. 1 1977,
1822.
(47) Wenkert, E.; McPherson, C. A. Synth. Commun. 1972, 2, 331.
(48) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.; Rosato, G. C.; Ursini,
A. J. Chem. Soc., Chem. Commun. 1993, 1798.
(49) Arbuzov, Yu. A.; Bolesov, I. G.; Bregadze, V. I.; Kolosov, M. N.;
Shemyakin, M. M.; El’perina, E. A. IzV. Akad. Nauk. SSSR, Ser. Khim.
1964, 310 (Chem. Abs. 1964, 60, 11959e).

4
J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
Heating 18 in n-octane at 110 °C provided ethyl 4,5-cyclohexa-
1H-pyrazole-3-carboxylate (19) in 59% isolated yield. Exposure
of 19 to BF3‚OEt2 in benzene, however, failed to give any
detectable quantities of ethyl 2-benzyl-cyclohex-1-ene carbox-
ylate (12), thereby ruling out this possibility.
pendently synthesized by treating ethyl 2-(diethylphosphor-
yloxy)-1-cyclohexenecarboxylate (33)50 with lithium diphen-
ylcuprate.51
Interestingly, there were no signs of the unsaturated ester 35
in this reaction since we were able to prepare an independent
sample from the endo-dig cyclization of the lithiate derived from
iodide 3452 and subsequent trapping with ethyl chloroformate.
When the reaction was carried out in pentane, ethyl R-fluoro-
cyclopentylidene acetate (28), ethyl 2-fluoro-1-cyclohexene
carboxylate (29), and ethyl 2-(fluoromethyl)-1-cyclopentene
carboxylate (30) were obtained as the only products. In contrast
to this finding, the reaction of 25 in acetonitrile afforded a 9:1
mixture of amides 31 and 32 as the sole products.
Cyclobutyl Derivatives. Treatment of the cyclobutyl analog
(i.e., 36) with BF3‚OEt2 in benzene afforded ethyl 2-phenylcy-
clopent-1-ene carboxylate (37) (51%) and ethyl 2-oxocyclo-
pentane carboxylate (39) (32%) as the major products accom-
panied by a small amount of ethyl 2-fluorocyclopent-1-ene
carboxylate (38) (5%). An authentic sample of 37 was prepared
Reaction of the R-methyl substituted diazo alcohol 21 derived
from 2-methylcyclohexanone with BF3‚OEt2 was next examined
so as to probe the selectivity of the rearrangement. Treatment
of 21 with BF3‚OEt2 in benzene afforded ethyl 2-benzyl-6-
methylcyclohex-1-ene carboxylate (22) as the major product.
When 21 was stirred with BF3‚OEt2 in nitromethane, a 1:1
mixture of methyl lactones 23 and 24 was isolated in 78% yield.
Cyclopentyl Derivatives. Exposure of ethyl 2-diazo-2-(1-
hydroxycyclopentyl)acetate (25) to freshly-distilled BF3‚OEt2
in the presence of benzene afforded 2-phenylcyclohex-1-ene
carboxylate (26) and 2-benzylcyclopent-1-enecarboxylate (27)
as the major products. When the reaction was repeated using
BF3‚OEt2 which had not been distilled, significant amounts of
by treating ethyl 2-(diethylphosphoryloxy)-1-cyclopentene car-
boxylate (40)50 with lithium diphenylcuprate.51 There were no
signs of the isomeric ester 42 in the crude reaction. An
independently synthesized sample of 42 was prepared by the
endo-dig cyclization of the lithiate derived from iodide 4152
followed by trapping with ethyl chloroformate.
Acyclic Derivatives. Intramolecular trapping of the cationic
intermediates by a tethered phenyl group was also investigated.
The reaction of diazo alcohol 43 with BF3‚OEt2 in benzene
afforded a variety of products (i.e., 44-52) as a result of
competitive trapping of the cationic intermediates by the solvent,
fluoride ion, water, the ester functionality, and the π-system of
the fluorinated derivatives 28 and 29 were obtained in addition
to 26 and 27 and is presumably due to the presence of some
hydrogen flouride in the BF3‚OEt2. Compound 26 was inde-
(50) Sum, F.-W.; Weiler, L. Can. J. Chem. 1979, 57, 1431.
(51) House, H. O.; Wilkins, J. M. J. Org. Chem. 1978, 43, 2443.
(52) Bailey, W. F.; Ovaska, T. V. J. Am. Chem. Soc. 1993, 115, 3080.

Reaction of R-Diazo-â-hydroxy Esters with BF3‚OEt2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996 5
the pendant phenyl group. Indenes 46 and 47 arise by
intramolecular trapping of a vinyl cation by the adjacent phenyl
ring. Products 45 and 51 can be rationalized as being formed
directly from the vinyldiazonium salt or Via a destabilized vinyl
cation intermediate (Vide infra). The formation of compounds
44, 46, 48, and 50 can be attributed to a 1,2-benzyl shift (Vide
infra) of the initially-formed vinyl cation and are found in larger
amounts (ca. 80%). The remaining products (49 and 52) are
derived from a 1,2-methyl shift of a destabilized vinyl cation
intermediate (Vide infra). When the reaction of 43 with BF3‚-
OEt2 was repeated in pentane, the yield of indenyl products
(46 and 47) was improved since competitive intermolecular
capture by benzene is no longer possible. The outcome of the
reaction of 43 with BF3‚OEt2 in acetonitrile was markedly
different. Specifically, the formation of the fluorinated products
44 and 45 was completely suppressed. Under these conditions,
enamide 53 was obtained as the major product in good yield
and lesser quantities of indenes 46 and 47 were also formed.
Scheme 1
leads to allylic cation 61. Bimolecular trapping of this primary
allylic cation with benzene affords 22, whereas intramolecular
cyclization with the adjacent ester group leads to 23. Capture
of aromatic substrates by vinyl cations has been the subject of
several studies.2a With nitromethane, some of the other lactone
Unifying Mechanism: Carbocation Cascade. A mecha-
nism which nicely accommodates the various products isolated
with these R-diazo-â-hydroxy esters is outlined in Scheme 1.
Complexation of the alcohol functionality of R-diazo-â-hydroxy
ester 10 with a Lewis acid occurs first, and this is followed by
generation of the cyclohexylidenediazonium salt. Loss of
nitrogen produces a highly reactive, destabilized, linear vinyl
cation 55. Ring expansion Via a 1,2-methylene shift results in
the formation of a more stable, bent cycloheptenyl vinyl cation
56. A subsequent 1,2-methylene shift resulting in ring contrac-
tion ultimately leads to the most stable allylic cation 57. This
cation is either trapped by the solvent or else undergoes
cyclization with the adjacent ester group to give the observed
lactone ring. Analogous mechanisms involving ring expansion
of the initially-generated linear vinyl cation to the more stable
bent vinyl cation followed by ring contraction to give an allylic
cation are perfectly consistent with the products obtained in the
reaction of R-diazo-â-hydroxy esters 21 and 25 with BF3‚OEt2.
The reaction of R-diazo-â-hydroxy ester 36 with BF3‚OEt2 also
appears to proceed via a ring expansion of the initially-generated
linear vinyl cation to afford a more stable bent vinyl cation;
however, a subsequent ring contraction apparently does not
occur since no products arising from the intermediacy of an
allylic cation are observed.
(i.e., 24) derived by path B (intermediate 63) is also formed.
Likewise, the seemingly very complex reactions of the acyclic
diazo alcohol 43 with BF3‚OEt2 in various solvents can easily
be accommodated by a mechanistic pathway similar to that
observed with its cycloalkanone-derived counterpart.
Computational Considerations. The driving force for
reactions proceeding through rearranging carbenium ions is
generally thermodynamic: products being derived from the most
stable cation(s). Qualitatively, this pattern is depicted in Scheme
1 by the transformation of destabilized vinyl cation 55 (V1) to
56 (V2) and onto the product-determining allyl cation 57 (A1).
To a first approximation, then, the transformation of various
R-diazo-â-hydroxy esters might be expected to yield primarily
A1 products. As discussed below, this is not the case.
In the case of the 2-methylcyclohexanone system (21), ring
expansion can occur by either of two pathways leading to the
rearranged cycloheptenyl cation. The relative migratory apti-
tudes of the methylene bonds should determine which pathway
is followed. The preferred migration (path A) corresponds to
rearrangement of the more substituted methylene group which
To explore the nuances of product distribution, we have
performed 6-31G* ab initio optimizations for cyclic and acyclic
intermediates 64-66 and 67-69, respectively, as the methyl
esters. The near linear geometries around CdC+sC for V1
(171-172°; cf. Table 1 supporting information) are in accord

6
J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
with many previous computational studies2d as well as the
recently reported MP2/6-31G* and GIAO-MP2 structure for the
cyclopropylcyclopropylidene-methyl cation.53,54 Exceptionally
expanded angles for the cyclic V2’s (147-168°) reflect a high
degree of internal strain in the attempt to linearize.
Figure 1. 6-31G* optimized transition states for the steps V1ˆ f V2ˆ
(67a f 70‡ f 68a and 75a f 77‡ f 76a) and V2ˆ f allyl (68b f 71‡
f 69b).
Product Distributions. The 6-31G* relative energies for V1,
V2, and A1 (Table 1; supporting information) are in accord with
expectation. A moderate energy gain for isomer V2 compared
to V1 (-3 to -8 kcal/mol) is accompanied by a large
stabilization for A1 (-27 to -31 kcal/mol). The computational
pattern applies to all systems under study and particularly favors
the cyclobutane series. Based on cation stabilization alone, one
would predict that products from the four- and five-membered
ring precursors, 36 and 25, respectively, would stem primarily
from the corresonding allyl cations.
Quantitatively, product types and ratios are strongly dependent
on ring size and solvent (Table 2). In benzene, for example,
six-ring 10 delivers products derived primarily from allyl-cation
66a (A1) with less than 10% from the first formed vinyl cation
64a (V1). Cyclobutane 36 provides derivatives exclusively from
the second vinyl cation 65c (V2). The five-membered ring 25
and acycle 43 yield a spread of products from all three
intermediates V1, V2, and A1. These results would not seem to
be governed exclusively by ground state thermodynamics for
cations stemming from different starting materials. Conse-
quently, we have examined the barriers between intermediates.
The transition state between V1 and V2 unencumbered by
cyclic constraints has been modeled by the fully optimized
saddle point structure 70q (Figure 1) linking 67a and 68a.
Similarly, structure 71q models the V2 to A1 transformation
between 68b and 69b. In the direction V1 f V2 f A1, the
activation energies are calculated to be 12.5 and 11.0 kcal/mol,
respectively. Key geometric elements of the transition structures
are depicted in Figure 1 and Table 1 (supporting information).
Most revealing are the bond angles around the CdC centers
undergoing bond breaking and bond making. The V1 f V2
barrier maximum 70q is characterized by an acetylene-like
structure with CdCsC bond angles of 175.1 and 158.0°.
Saddle point 71q exhibits the same angle at 159.6° and closely
Figure 2. 6-31G* optimized hypersurface for the acyclic migrations
V1ˆ f V2ˆ f A1 (kcal/mol). Structures 68a and 68b are arbitrarily
scaled to the same energy.
resembles the approximate transition state for hydride migration
connecting the 2-propenyl and allyl cations.55
Figure 2 depicts the 6-31G* V1 f V2 f A1 energy profile
for the acyclic transformations. Among other things, it il-
lustrates that the barrier height for the initial 1,2-shift between
V1 and V2 (70q ) is of the same order of magnitude as the
transition state 71q leading to the allyl cation. The implication
of the structural and energetic analysis is clear. Where ring
strain is likely to play a role, ring expansion will be favored
(53) Sustmann, R.; Williams, J. E.; Dewar, M. J. S.; Allen, L. C.;
Schleyer, P. v. R. J. Am. Chem. Soc. 1969, 91, 5350.
(54) Siehl, H.- U.; Mu¨ller, T.; Gauss, J.; Buzek, P.; Schleyer, P. v. R. J.
Am. Chem. Soc. 1994, 116, 6384.
(55) Radom, L., Hariharan, P. C.; Pople, J. A.; Schleyer, P. v. R. J. Am.
Chem. Soc. 1973, 95, 6531.

Reaction of R-Diazo-â-hydroxy Esters with BF3‚OEt2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996 7
Table 2. Normalized Distributions of V1, V2, and Allyl Products
from Reactions of R-Diazo-â-hydroxy Esters with BF3‚OEt2 in
Various Solvents
normalized product ratios, % (total yield, %)
solvent and cationic
intermediates
10
25
36
43
Benzene
V1
V2
A1
6
33
41
26
22
70
8
100
94
(92)
(76)
(89)
(94)
Pentane
V1
V2
A1
36
53
11
34
53
13
Figure 3. Comparison of 6-31G* optimized endocyclic ring ring angles
for unsolvated and solvated V2 cation intermediates.
100
(75)
(79)
(76)
CH3CN
Given the cationic nature of the subsequent intermediates, the
ether is most likely retained within the substrate solvent cage.
With the release of dinitrogen and the formation of a vinyl
cation, ether can serve as a cation coordinating agent to give
the vinyl cation equivalent (72) of the classical and commercially
available Meerwein reagent, [(Et)3O+][BF4-]. One consequence
of this interpretation is that without an abundance of easily
exchanged ether, BF3 will remain strongly coordinated to the
hydroxide ion.
V1
V2
A1
6
19
75
90
10
15
85
(81)
(61)
(72)
and ring contraction will be disfavored. As smaller rings are
involved, the first migration barrier will fall relative to the
second.
Thus, cyclohexane 10 (64a) manages expansion to the seven-
ring V2 chair 65a and subsequent contraction to six-ring allyl
cation 66a with ease. Five-ring 25 (64b) negotiates the same
path but surmounts the V2 f A1 barrier with greater difficulty
as indicated by significant capture of V1 and V2. The uniquely
strained cyclobutane 66b appears to ring expand rapidly with a
calculated energy gain of 8.2 kcal/mol (Table 1, supporting
information). Then, however, it is trapped at V2 unable to pay
the energetic price required to reach or mimic the near linear
transition state 71q. The acyclic precursor 43 differs from the
cyclic species in two important ways. First, it carries an
intramolecular phenyl group positioned to dissipate cationic
charge in subsequent intermediates by entropically favorable
ring closure. Second, it proceeds to linear vinyl cations
analogous to 67 and 68 with steric features absent in the cyclic
cases. An array of products partitioned along all three V1/V2/
A1 channels is the consequence.
Possible Role of Et2O in BF3‚OEt2. The most striking
structural feature of the optimized cyclic V2 vinyl cations 65a-c
is ring distortion in response to the cation's effort to linearize.
The strained seven-, six-, and five-membered rings display
CdC+sCH2 bond angles of 167.8, 156.1 and 146.7°, respec-
tively (Table 1, supporting information). Acycles 68a and b,
on the other hand, enjoy outstretched angles of 175.4 and 177.1°.
While the distorted gas phase cyclic structures may have
transient existence in the reactions of R-diazo-â-hydroxy esters,
an important stabilizing factor can be envisaged in the following
sequence of events.56
To examine other possible consequences of ether-vinyl cation
coordination, structures 73-76 incorporating a molecule of
dimethyl ether were likewise optimized at the 6-31G* level.
The disturbing geometric distortions within the cyclic vinyl
cations are abated. The 147-168o CdC+sC angles of the
cyclic carbocations have dropped to 117-127° for rings 74a-c
(Table 3, supporting information). Bond angles are slightly
larger than those found in normal alkenes (75a 133.3°),
reflecting the presence of a solvated rather than a covalently
bound vinyl cation. At the same time, the relatively normal
ring geometries for the solvated structures are in line with
stability expectations for compounds engaging in both unimo-
lecular and bimolecular reactions. Figure 3 underscores the
point by comparing ring angles for solvated and unsolvated
6-31G* V2 vinyl cations.
Scheme 2
Another outcome of the hypothesis of ether as reagent in the
present series of reactions is that V1 vinyl cations are no longer
linear. The CdC+sC angles for 73a-c fall within the range
130-135° in contrast to 171-173° for the gas phase counter-
parts 64a-c (Table 1 and 3, supporting information). Likewise,
the solvated acyclic V2 cation 76a sustains a bond angle for
the cationic moiety of 132.1° Vs 175.4° for the unsolvated analog
68a. Furthermore, in response to ether participation, the very
tight bond lengths around uncoordinated CdC+ are relaxed
considerably. For example, the CH2C+)C(CO)CH2 fragment
in 65a displays bond distances of 1.415, 1.272, and 1.531 Å
that shift to 1.509, 1.321, and 1.524 Å in 74a.
In order to promote the transformation of diazoester, BF3‚-
OEt2 is obligated to relinquish an equivalent of diethyl ether.

8
J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
The satisfying structural characteristics of the solvated vinyl
cations are complemented by solvation energies from 43-68
kcal/mol (Esolv(a-b/c), Table 3, supporting information). Not
surprisingly, the value increases with decreasing ring size.
While the differential stabilization is moderate for the V1 series
73a-c (∆Esolv ) 3.7 and 6.7 kcal/mol), it is substantial for the
cyclic V2’s, 74a-c (7.4 and 22.2 kcal/mol). The operation of
a kinetic component for the product distributions of Table 2 is
again supported by the Erel’s of Table 3 (supporting information).
A completely thermodynamic bias would predict six-ring 10
and five-ring 25 to deliver only V1 and V2 products, respectively,
in contrast to the experimental outcomes.
A novel feature of the cationic intermediates in the present
work is substitution by the electron withdrawing carboethoxy
moiety. One implication concerns the fact that vinyl cations
rearrange both by ring contraction and expansion.2 Methyl
analogs 81a and 82a, for example, have been shown to
interconvert under solvolytic conditions in EtOH and TFE. In
this case, transformation to allyl cation product 83a was not
observed.58 The differences underscore one of the character-
istics of destabilized vinyl cation intermediates. Whereas the
methyl substituted cations are nearly isoenergetic, the corre-
sponding equilibrium for carbomethoxy derivatives 81b and 82b
lies far to the right. The calculated energy difference of -3.1
kcal/mol (Table 1, supporting information) translates to an
approximate relative population of 1:200 (0.5:99.5%), respec-
tively. It has been estimated that the effectiveness of R-sub-
stituents to stabilize a vinyl cation follow the order C6H5 .
CH2dCH2 . CH3 . H, where the overall gap is 60 kcal/mol.
Of this, the CH3/H difference amounts to 25 kcal/mol.59
Obviously, the CO2Me occasions still greater destabilization.
Consistent with the destabilizing effect of CO2R, we propose
that generation of vinyl cations in the presence of ether leads
to long-lived oxonium intermediates analogous to Meerwein
reagents (e.g., 73-76). Cation-solvent association accompanied
by significant geometry variation applies as well to other vinyl
cations in the presence of basic but weak nucleophiles. Under
favorable conditions, complex formation ought to be perceived
by techniques such as NMR. Conceivably, the unexpectedly
poor agreement between measured and calculated 13C chemical
shift for the trivalent carbon in the cyclopropylcyclopropylidene-
methyl cation stems from a bent geometry in the presence of
FSO3H.54
The ether solvated transition state analog of 70q, 77q, has been
located with the geometric variables depicted at the bottom of
Figure 1. Inspection of the two structures demonstrates a very
similar geometry with the molecule of dimethyl ether in 77q at
a distance of nearly 3.0 Å. Migration of the methyl has
obviously displaced the solvent as one might expect for an easily
dislodged leaving group. The calculated stabilization of 77q
by the ether molecule is 8.8 kcal/mol (Esolv, Table 3, supporting
information). This is rather meager when compared with the
45-68 kcal/mol found for solvent association with various vinyl
cations in the ground state. We do not take this to imply that
the barrier for migration from 75a to 77q is 57.5 kcal/mol (Table
3, supporting information). Clearly, solvent orientation trans
to the migrating group is a less favorable location than other
centers around the transition state. These have not been
explored in the present study.
Concluding Remarks
Boron trifluoride etherate promoted transformation of R-diazo-
â-hydroxy esters in various solvents leads to a diversity of
products. Vinyl cation formation, rearrangement (V1 f V2 f
allyl) and concomitant carbenium ion trapping along the reaction
pathway accommodate both product structure and distribution
from the different reaction channels. The driving force for many
carbocation rearrangements, including vinyl cations, is generally
considered to be formation of the more stable carbenium ion.
For example, the principle has been applied to vinyl triflate
solvolysis25 and the formation of allyl cations from acetylenes
in FSO3HSBF5 at low temperature.57 In the present instance,
our 6-31G* calculations likewise predict increasing stability for
V1 f V2 f A1. However, diversion of the products early in
the pathway prior to formation of the final A1 carbenium ions
suggests the operation of a kinetic component as well. In the
cyclic cases, the energy barriers corresponding to V1 f 70q
and V2 f 71q (Figure 2) are expected to be raised by comparison
with the acyclic system permitting the trapping of V1 and V2
as recorded in Table 2.
Finally, we have discussed the formation of allyl cations from
10, 25, and 43 as proceeding through a pair of sequential 1,2-
(56) Variations on this mechanism, especially when catalytic BF3 is used
have been suggested by the reviewers and are shown below:
Support for the kinetic interpretation is found in the observa-
tion that hydride and alkyl groups alike are known to participate
in 1,2-shifts to the vinyl cation CdC+ to produce allyl cations.2c,d
Yet to our knowledge, no 1,2-migrations in which the resultant
allylic ion is primary have been reported. By contrast, each of
the vinyl cation precursors studied here (10, 25, and 43) leads
to such an intermediate (Scheme 1). A 1,2-hydride shift in 78
(i.e., 10 and 25) would have yielded the secondary internal allyl
cation 79. That CH2 has shifted instead of H, in spite of the
strain-inducing ring contraction to 80, argues for a decisive
stereoelectronic component in the presumably concerted process.
The orientation of migrating methyl in 71q (Figure 1) illustrates
the planar array of atoms required to achieve productive orbital
overlap. Saturated ring carbons R to the cationic center in cycles
such as 78, but not the attached hydrogens, can assume a
relatively low energy transition state geometry in accord with
a kinetic driving force for the reaction.
(57) Olah, G. A.; Mayr, H. J. Am. Chem. Soc. 1976, 98, 7333.
(58) Hanack, M.; Fuchs, K. A., unpublished; reported in ref 2d, pp 464-
465.
(59) Hehre, W. J.; Ditchfield, R.; Radom, L.; Pople, J. A. J. Am. Chem.
Soc. 1970, 92, 4796; Apeloig, Y.; Schleyer, P. v. R. J. Org. Chem. 1977,
42, 3004.

Reaction of R-Diazo-â-hydroxy Esters with BF3‚OEt2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996 9
and concentrated under reduced pressure. The residue was subjected
to flash silica gel chromatography to afford the pure ethyl 2-diazo-3-
hydroxy carboxylate.
shifts. In principle, allyl cations can arise directly from V1 by
means of a 1,3-carbon shift, thereby avoiding altogether the
strained cyclic vinyl cations V2. Although 1,4-halogen and 1,5-
hydride migrations to vinyl cations are known,2 1,3-shifts do
not seem to have been reported. Indeed, rearrangement of the
putative vinyl cation obtained by adding tert-butyl cation to
2-butyne has been interpreted as a double 1,2-methyl shift, the
1,3-methyl migration rejected by deuterium labeling.60 To test
for the possible operation of a 1,3-trans-formation in 10, D-labels
were introduced into 84 starting from cyclohexanone.
Reaction of Ethyl 2-Diazo-2-(1-hydroxycyclohexyl)acetate (10)
with Boron Trifluoride Etherate. Ethyl 2-diazo-2-(1-hydroxycyclo-
hexyl)acetate (10) was prepared in 88% yield as a yellow oil using 2.0
g (20 mmol) of cyclohexanone: IR (neat) 3473, 2086, 1687, 1296,
1
and 1104 cm-1; H-NMR (300 MHz, CDCl3) δ 1.29 (t, 3H, J ) 7.1
Hz), 1.33-1.91 (m, 10H), 3.51 (s, 1H), and 4.24 (q, 2H, J ) 7.1 Hz);
13C-NMR (75 MHz, CDCl3) δ 14.0, 14.3, 21.9, 24.3, 25.1, 27.5, 36.3,
60.6, 70.1, and 167.1.
.
To a cold (0 °C) mixture of 4.7 mL (37 mmol) of BF3 Et2O in 40
mL of pentane was added dropwise 5.30 g (25 mmol) of diazoester 10
in 20 mL of pentane. After stirring for 2 h, the reaction was quenched
with a saturated NaHCO3 solution, extracted with ether, washed with
brine, and dried over MgSO4. Concentration of the mixture under
reduced pressure followed by silica gel column chromatography gave
2.60 g (75%) of tetrahydro-1(3H)-isobenzofuranone (11) as a white
solid: mp 50-51 °C (lit.61 mp 53-54 °C); IR (CCl4) 1750, 1679, 1438,
1
1240, and 1021 cm-1; H-NMR (90 MHz, CDCl3), δ 1.45-2.06 (m,
4H), 2.07-2.41 (m, 4H), and 4.68 (s, 2H). Anal. Calcd for C8H10O2:
C, 69.55; H, 7.30. Found: C, 69.50; H, 7.30.
To a cold (5 °C) mixture of 0.90 mL (7.1 mmol) of BF3‚Et2O in 5
mL of benzene was added dropwise 1.0 g (4.7 mmol) of diazoester 10
in 5 mL of benzene. After stirring for 2 h, the reaction was quenched
with a saturated aqueous NaHCO3 solution. The mixture was extracted
with ether, and the extracts were washed with brine, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified
by flash silica gel chromatography to give 0.05 g (6%) of R-fluoro-
cyclohexylideneacetate (13): 1H-NMR (90 MHz, CDCl3) δ 1.30 (t,
3H), 1.60 (m, 6H), 2.32 (m, 2H), 2.70 (m, 2H), and 4.25 (q, 2H); m/e
186 (61), 158, 157, 141, 139, 104, and 91; GC purity: g99%. Further
elution afforded 0.85 g (74%) of ethyl 2-benzyl-cyclohex-1-enecar-
boxylate (12) as a pale yellow oil: IR (neat) 2934, 1706, 1223, and
BF3‚OEt2 promoted rearrangement led to a single deuterated
product. Compound 85 with the CD2C(d)CO2Et label is
consistent only with two sequential 1,2-shifts. A 1,3-rearrange-
ment to an allyl cation would have afforded the unobserved
CD2C(d)CD2Ph pattern.
Experimental Section
1
1046 cm-1; H-NMR (300 MHz, CDCl3) δ 1.27 (t, 3H, J ) 7.1 Hz),
Proton and carbon magnetic resonance spectra were taken on a
Varian EM 390, a Bruker AC 200, and a GE QE-300 spectrometer,
and the chemical shifts are reported on the δ scale relative to
tetramethylsilane. 13C-NMR spectra were recorded on a GE QE-300
75 MHz spectrometer. Mass spectra were determined with a VG MM-
7070S mass spectrometer at an ionizing voltage of 70 eV. Melting
points were determined on a Thomas-Hoover capillary melting point
apparatus and are uncorrected. Unless otherwise noted, all reactions
were performed in oven dried glassware under an atmosphere of dry
argon. Solutions were evaporated under reduced pressure with a rotary
evaporator, and the residue was flash chromatographed on a silica gel
column using a hexane-ethyl acetate mixture as the eluent unless
specified otherwise.
Product Elucidation Studies. Some of the products obtained from
the reaction of the R-diaazo-â-hydroxy esters with BF3‚OEt2 correspond
to known compounds. These include lactones 11,61 23,62 and 24,62 and
esters 16,63 17,64 and 37.65 The spectral properties of these compounds
have been compared to independently synthesized material and were
identical in every detail.
General Procedure for the Preparation of Ethyl 2-Diazo-3-
hydroxy Carboxylates. A cold (-10 °C) solution of lithium diiso-
propylamide [prepared by the addition of n-butyllithium in hexane (20
mL of a 2.5 M solution) to a solution of diisopropylamine (5.05 g) in
THF (30 mL)] was added during 30 min to a stirred solution of the
appropriate ketone (41 mmol) and ethyl diazoacetate (41 mmol) at -78
°C. The mixture was allowed to stir at -78 °C for 2 h at which time
the reaction was quenched with a saturated NH4Cl solution and extracted
with ether. The combined organic extracts were washed with saturated
aqueous NaHCO3 solution and brine, dried over anhydrous MgSO4,
1.51-1.64 (m, 4H), 1.99-2.03 (m, 2H), 2.33-2.42 (m, 2H), 3.71 (s,
2H), 4.20 (q, 2H, J ) 7.1 Hz), and 7.23 (m, 5H); 13C-NMR (75 MHz,
CDCl3) δ 14.1, 14.2, 22.0, 22.1, 26.6, 30.2, 40.6, 60.0, 125.8, 126.2,
128.1, 139.7, 145.4, and 169.1. Anal. Calcd for C16H20O2: C, 78.65;
H, 8.25. Found: C, 78.60; H, 8.25. Further elution of the silica gel
column afforded 0.08 g (12%) of tetrahydro-1(3H)-isobenzofuranone
(11).
To a cold (10 °C) mixture of 0.78 mL (6.3 mmol) of BF3‚Et2O in
3.0 mL of p-xylene was added dropwise 0.90 g (4.24 mmol) of
diazoester 10 in 3.0 mL of p-xylene. After stirring for 2 h, the reaction
was quenched with a saturated NaHCO3 solution, extracted with ether,
washed with brine, and dried over MgSO4. Concentration under
reduced pressure followed by column chromatography on silica gel
gave 0.54 g (47%) of ethyl 2-(2,5-dimethylbenzyl)-cyclohex-1-enecar-
boxylate (14) as a pale yellow oil: IR (neat) 1708, 1630, 1496, 1220,
1
and 1043 cm-1; H-NMR (300 MHz, CDCl3) δ 1.24 (t, 3H, J ) 7.0
Hz), 1.52-1.65 (m, 4H), 1.94-1.96 (m, 2H), 2.21 (s, 3H), 2.27 (s,
3H), 2.33-2.37 (m, 2H), 3.72 (s, 2H), 4.17 (q, 2H, J ) 7.0 Hz), and
6.95 (m, 3H); 13C-NMR (75 MHz, CDCl3) δ 14.1, 19.1, 20.9, 22.1,
22.2, 26.7, 30.3, 37.9, 59.9, 126.4, 126.5, 129.5, 129.7, 133.2, 135.0,
137.6, 145.6, and 169.1. Anal. Calcd for C18H24O2: C, 79.36; H, 8.89.
Found: C, 79.04; H, 8.73.
To a cold (0 °C) mixture of 0.90 mL (7.1 mmol) of BF3‚Et2O in 5
mL of acetonitrile was added dropwise 1.0 g (4.7 mmol) of diazoester
10 in 5 mL of acetonitrile. After stirring for 2 h, the reaction was
quenched with a saturated aqueous NaHCO3 solution. The mixture was
extracted with ether, and the extracts were washed with brine, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by flash silica gel chromatography to give 0.040 g (5%)
of an inseparable mixture of the E- and Z-isomers of diene 17:64 1H-
NMR (90 MHz, CDCl3) δ 1.30 (t, 2 × 3H), 1.75 (m, 2 × 2H), 2.15
(m, 2 × 2H), 2.40 (m, 2H), 3.00 (m, 2H), 4.07 (q, 2 × 2H), 5.47 (s,
1H), 5.60 (s, 2H), 6.20 (m, 2 × 1H), and 7.50 (m, 1H). Anal. Calcd
for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.15; H, 8.55. Further
elution gave 0.130 g (15%) of 2-hydroxy-1-cycloheptenecarboxylate
(16):63 1H-NMR (90 MHz, CDCl3) δ 1.10-2.70 (m, 5 × 2H), 1.25 (t,
3H), 3.50 (t, 0.65H), 4.16 (q, 2H), and 12.40 (s, 0.35H). Anal. Calcd
(60) Capozzi, G.; Lucchini, V.; Marcuzzi, F.; Melloni, G. Tetrahedron
Lett. 1976, 717.
(61) Butina, D.; Sondheimer, F. Synthesis 1980, 543.
(62) Miura, M.; Okuro, K.; Hattori, A.; Nomura, M. J. Chem. Soc., Perkin
Trans. I 1989, 73.
(63) Freiermuth, B.; Wentrup, C. J. Org. Chem. 1991, 56, 2286.
(64) Bensel, N.; Ho¨hn, J.; Morschall, H.; Weyerstahl, P. Chem. Ber. 1979,
112, 2256.
(65) Holmberg, G.; von Weymarn, T.; Malmstrom, F. Acta Acad. Abo.
Math Phys. 1969, 29, 4.

10 J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
for C10H16O3: C, 65.19; H, 8.75. Found: C, 65.25; H, 8.70. Further
elution afforded 0.15 g (23%) of lactone 11 as well as 0.40 g (38%) of
ethyl 2-acetamidomethyl-1-cyclohexene carboxylate (15): 1H-NMR
(CDCl3) δ 1.25 (t, 3H, J ) 7.1 Hz), 1.40-1.70 (m, 4H), 2.00 (s, 3H),
2.10-2.30 (m, 4H), 3.95 (d, 2H), 4.15 (q, 2H, J ) 7.1 Hz), and 6.20
(brs, 1H, NH); 13C-NMR (CDCl3) δ 14.2, 20.0, 21.8, 23.3, 26.1, 30.9,
42.3, 65.8, 127.9, 147.1, 168.6, and 169.8; m/e 225 (16), 179 (75),
151 (87). Anal. Calcd for C12H19NO3: C, 63.98; H, 8.50; N, 6.22.
Found: C, 63.95; H, 8.40; N, 6.25.
(s, 2H); (compound 24) δ 1.40 (d, 3H, J ) 6.7 Hz), 1.67-1.89 (m,
4H), 2.29-2.35 (m, 4H), and 4.90 (q, 1H, J ) 6.7 Hz); 13C-NMR (75
MHz, CDCl3) (mixture) δ 17.7, 17.8, 18.6, 19.3, 21.0, 22.3, 23.4, 25.4,
29.9, 71.1, 78.7, 125.1, 129.2, 160.8, 164.7, 172.9, and 173.3; HRMS
calcd for C9H12O2 152.0837, found: 152.0837.
Reaction of Ethyl 2-Diazo-2-(1-hydroxycyclopentyl)acetate (25)
with Boron Trifluoride Etherate. Ethyl 2-diazo-2-(1-hydroxycyclo-
pentyl)acetate (25) was prepared in 98% yield as a yellow oil by using
5.0 g of cyclopentanone (59.5 mmol) and 6.79 g of ethyl diazoacetate
1
(59.5 mmol): IR (neat) 3466, 2086, 1687, and 1296 cm-1; H-NMR
Preparation and Reaction of Ethyl 2-Diazo-2-(cyclohexenyl)-
acetate (18) with Boron Trifluoride Etherate. To a cold (-5 to -10
°C) solution containing 2.12 g (10.0 mmol) of diazoester 10 in 40 mL
of pyridine was added 6.13 g (40.0 mmol) of phosphoryl chloride with
stirring. The resulting mixture was stirred for 6.5 h at 0 °C and was
then allowed to warm to room temperature. The solution was filtered
through a pad of Celite, extracted with pentane, washed with water,
and dried over MgSO4. Evaporation of the solvent gave 1.63 g (84%)
of ethyl 2-diazo-2-(cyclohexenyl)acetate (18) as an orange oil which
was sufficiently pure for use in the next step: IR (neat) 2925, 2071,
and 1701 cm-1; 1H-NMR (90 MHz, CDCl3) δ 1.25 (t, 3H, J ) 7 Hz),
1.45-1.89 (m, 4H), 1.99-2.30 (m, 4H), 4.30 (q, 2H, J ) 7 Hz), and
6.03-6.24 (m, 1H). Treatment of 18 with BF3‚Et2O in the presence
of benzene resulted only in nitrogen evolution and the formation of a
complex mixture of products which did not contain any detectable
quantities of ethyl 2-benzyl-cyclohex-1-enecarboxylate (13). A sample
of ethyl 4,5-cyclohexa-1H-pyrazole-3-carboxylate (19) was prepared
by heating a 1.10 g (5.66 mmol) sample of 18 in 30 mL of n-octane at
110 °C for 1 h. The mixture was cooled to room temperature and
concentrated under reduced pressure, and the white crystalline solid
that precipitated was recrystallized from hexane to give 650 mg (59%)
of ethyl 4,5-cyclohexa-1H-pyrazole-3-carboxylate (19): mp 90-91 °C
(lit.43 mp 90-91 °C); IR (CCl4) 3445, 3018, 1716, 1438, and 1211
cm-1; 1H-NMR (300 MHz, CDCl3) δ 1.31 (t, 3H, J ) 7.5 Hz), 1.65-
1.9 (m, 4H), 2.59-2.87 (m,4H), 4.35 (q, 2H, J ) 7.5 Hz), and 10.8
(300 MHz, CDCl3) δ 1.30 (t, 3H, J ) 7.1 Hz), 1.67-1.98 (m, 6H),
1.99-2.11 (m, 2H), 3.29 (s, 1H), and 4.25 (q, 2H, J ) 7.1 Hz); 13C-
NMR (75 MHz, CDCl3) δ 14.2, 22.8, 39.1, 60.6, 78.3, and 166.9.
To a cold (5 °C) solution containing 0.74 mL (6.0 mmol) of BF3‚-
Et2O in 3 mL of benzene was added dropwise 740 mg (3.73 mmol) of
diazoester 25 in 3 mL of benzene. After stirring for 2 h, the reaction
was quenched with a saturated NaHCO3 solution, extracted with ether,
washed with brine, and dried over MgSO
.
Concentration under
4
reduced pressure and flash column chromatography on silica gel gave
71 mg (21%) of ethyl 2-phenylcyclohex-1-enecarboxylate (26): IR
(neat) 2932, 1695, 1246, and 1051 cm-1; 1H-NMR (300 MHz, CDCl3)
δ 0.83 (t, 3H, J ) 7.1 Hz), 1.75 (m, 4H), 2.40 (m, 4H), 3.86 (q, 2H,
J ) 7.1Hz), and 7.22 (m, 5H);
13C-NMR (75 MHz, CDCl3) δ 13.5,
21.9, 22.5, 26.6, 32.6, 60.0, 126.8, 126.9, 127.9, 128.0, 143.5, 145.5,
and 170; m/e 230 (M+), 201, 184 (base), 156, 129, 115 and 91. Anal.
Calcd for C15H18O2: C, 78.22; H, 7.88. Found: C, 77.91; H, 7.66.
The minor product isolated from the silica gel column chromatog-
raphy column (48 mg, 16%) was identified as ethyl 2-benzylcyclopent-
1-enecarboxylate (27) on the basis of its spectral properties: IR (neat)
2954, 1702, 1637, 1253, and 1101 cm-1; 1H-NMR (300 MHz, CDCl3)
δ 1.31 (t, 3H, J ) 7.0 Hz), 1.68-1.81 (m, 2H), 2.38 (m, 2H), 2.67 (m,
2H), 3.95 (s, 2H), 4.23 (q, 2H, J ) 7.0 Hz), and 7.23 (m, 5H); 13C-
NMR (75 MHz, CDCl3) δ 14.3, 21.3, 33.7, 36.1, 37.8, 59.8, 126.1,
128.3, 128.8, 139.2, 156.8, and 166.2; m/e 230 (M+), 201, 184 (base),
155, 129, 115, 91, and 77. Anal. Calcd for C15H18O2: C, 78.22; H,
7.88. Found: C, 78.09; H, 7.56.
.
(brs, 1H, J ) 7.5 Hz). Treatment of 19 with BF3 Et2O in the presence
of benzene also failed to give any detectable quantities of ethyl
2-benzylcyclohex-1-enecarboxylate (13).
The reaction was repeated using BF3‚Et2O which had not been
distilled. A solution containing 1.0 g (5.05 mmol) of diazoester 25 in
10 mL of benzene was added dropwise during 20 min to a solution of
Reaction of Ethyl 2-Diazo-2-(1-hydroxy-2-methylcyclohexyl)-
acetate (21) with Boron Trifluoride Etherate. Ethyl 2-diazo-2-(1-
hydroxy-2-methylcyclohexyl)acetate (21) was obtained in 53% yield
as a yellow oil by using 1.0 g (8.9 mmol) of 2-methylcyclohexanone:
IR (neat) 3480, 2086, 1666, 1367, 1296, and 1104 cm-1; 1H-NMR (300
MHz, CDCl3) δ 0.94 (d, 3H, J ) 6.6 Hz), 1.27 (t, 3H, J ) 7 Hz),
1.40-1.81 (m, 8H), 1.99-2.03 (m, 1H), 3.74, (s, 1H), and 4.22 (q,
2H, J ) 7 Hz); 13C-NMR (75 MHz, CDCl3) δ 14.4, 15.9, 21.5, 25.3,
30.0, 33.9, 37.9, 38.2, 60.7, 71.8, and 167.7.
.
0.93 mL (7.6 mmol) of BF3 Et2O in 10 mL of benzene kept under
vigorous magnetic stirring at 5 °C under a nitrogen blanket. After
stirring for 15 min, the reaction mixture was diluted with a saturated
NaHCO3 solution and extracted with EtOAc. The combined organic
phases were washed with brine and dried over anhydrous Na2SO4. After
evaporation of the solvent, the residue was submitted to medium
pressure chromatography eluting with light petroleum ether. In addition
to compounds 26 (13%) and 27 (20%), 0.21 g (25%) of ethyl
R-fluorocyclopentylidene acetate (28) was obtained: 1H-NMR (CDCl3)
δ 1.35 (t, 3H, J ) 7.1 Hz), 1.75 (m, 4H), 2.55 (m, 2H), 2.70 (m, 2H),
and 4.30 (q, 2H, J ) 7.1 Hz); 13C-NMR (CDCl3) δ 12.7, 25.6, 26.9,
30.5, 30.9, 61.5, 139.0, 141.0 (CFdC), 141.3, 143.9, (CFdC), and
160.9; m/e 172 (M+), 144 (base), 127, 115, 99, 79, and 59; GC purity:
g99%.
Further elution with the same solvent afforded 0.22 g (18%) of ethyl
2-fluoro-1-cyclohexene carboxylate (29): 1H-NMR (CDCl3) δ 1.26 (t,
3H, J ) 7.1 Hz), 1.57 (m, 2H), 1.70 (m, 2H), 2.26 (m, 4H), 4.13 (q,
2H, J ) 7.1 Hz); 13C-NMR (CDCl3) δ 14.1, 21.7, 22.0, 24.3, 26.7,
27.2, 60.2, 108.0 (CFdC), 162.6, 165.7 (CFdC), 168.2; m/e 172 (M+),
144, 127 (base), 99, and 79; GC purity: g99%.
When the reaction was carried out in pentane, in addition to com-
pounds 28 (28%) and 29 (42%), it was also possible to isolate ethyl
2-fluoromethyl-1-cyclopentenecarboxylate (30) (9%): 1H-NMR (CDCl3)
δ 1.25 (t, 3H, J ) 7.1 Hz), 1.82 (m, 2H), 2.60 (m, 4H), 4.15 (q, 2H,
J ) 7.1 Hz), and 4.40 (s, 2H); 13C-NMR (CDCl3) δ 14.2, 21.5, 29.6,
33.8, 37.2, 60.5, 129.0 (FCH2CdC), 159.6 (FCH2CdC), and 166.8;
m/e 172 (M+), 170, 142, 127, 124, 114, 86, 68 (base), and 55. Anal.
Calcd for C15H19O2: C, 77.89; H, 8.28. Found: C, 77.90; H, 8.30.
The reaction of 25 was also carried out in acetonitrile. A solution
of 1.0 g (5.05 mmol) of 25 in 15 mL of acetonitrile was added dropwise
during 20 min to a solution containing 0.93 mL (7.6 mmol) of BF3‚-
Et2O in 15 mL of acetonitrile kept under vigorous magnetic stirring at
0 °C under a nitrogen atmosphere. After stirring for 15 min, the reaction
To a cold (5 °C) mixture containing 0.46 mL (3.7 mmol) of BF3‚-
Et2O in 2.5 mL of benzene was added dropwise 570 mg (2.52 mmol)
of diazoester 21 in 2.5 mL of benzene. After stirring for 2 h, the
reaction was quenched with a saturated NaHCO3 solution, extracted
with ether, washed with brine, and dried over MgSO4. The solvent
was removed under reduced pressure, and the residue was chromato-
graphed on a flash silica gel column. The major fraction contained
117 mg (18%) of ethyl 2-benzyl-6-methylcyclohex-1-enecarboxylate
(22) as a pale yellow oil: IR (neat) 2924, 1707, 1449, 1218, and 1043
cm-1; 1H-NMR (300 MHz, CDCl3) δ 1.04 (d, 3H, J ) 7 Hz), 1.28 (t,
3H, J ) 7 Hz), 1.32-1.89 (m, 4H), 1.92 (m, 4H), 2.74 (m, 2H), 3.48
(d, 1H, J ) 14.2 Hz), 3.58 (d, 1H, J ) 14.2 Hz), 4.23 (q, 2H, J ) 7
Hz), and 7.69 (m, 5H); 13C-NMR (75 MHz, CDCl3) δ 14.2, 19.3, 20.2,
29.5, 30.2, 30.5, 40.8, 60.1, 125.9, 128.2, 128.8, 132.6, 139.7, 141.4,
and 170.0. Anal. Calcd for C17H22O2: C, 79.02; H, 8.59. Found: C,
79.13; H, 8.62.
.
To a cold (0 °C) mixture of 0.45 mL (3.7 mmol) of BF3 Et2O in 2.5
mL of nitromethane was added dropwise 550 mg (2.43 mmol) of
diazoester 21 in 2.5 mL of nitromethane. After stirring for 2 h, the
reaction was quenched with a saturated NaHCO3 solution, extracted
with ether, washed with brine, and dried over MgSO4. Concentration
under reduced pressure followed by flash silica gel chromatography
afforded 290 mg (78%) of an inseparable 1:1 mixture of methyl lactones
1
23 and 24:62 IR (neat) 2932, 1743, 1672, 1446, and 1022 cm-1; H-
NMR (300 MHz, CDCl3) (compound 23) δ 1.18 (d, 3H, J ) 7.1 Hz),
1.67-1.89 (m, 4H), 2.18-2.21 (m, 2H), 2.51-2.54 (m, 1H), and 4.69

Reaction of R-Diazo-â-hydroxy Esters with BF3‚OEt2
J. Am. Chem. Soc., Vol. 118, No. 1, 1996 11
mixture was diluted with a saturated NaHCO3 solution and extracted
with ethyl acetate. The combined organic phase was washed with brine
and dried over anhydrous Na2SO4. After evaporation of the solvent,
the residue was submitted to flash silica gel chromatography using a
85:15 light petroleum-ethyl acetate mixture. The major fraction
isolated from the column contained 0.50 g (55%) of ethyl R-acetami-
docyclopentylidene acetate (31): 1H-NMR (CDCl3) δ 1.10 (t, 3H, J )
7.1 Hz), 1.45 (m, 2H), 1.95 (s, 3H), 2.15 (m, 2H), 2.90 (m, 2H), 4.10
(q, 2H, J ) 7.1 Hz), and 11.40 (br s, 1H, NH); 13C-NMR (CDCl3) δ
13.6, 21.2, 21.3, 23.7, 27.9, 59.6, 103.8 (CdCN), 151.5 (CdCN), 168.1
(CON), and 169.3 (CO2); m/e 211 (M+), 165 (base), 137, 123, 96, 68,
and 55. Anal. Calcd for C11H17NO3: C, 62.54; H, 8.11; N, 6.63.
Found: C, 62.50; H, 8.10; N, 6.70. Further elution with the same
solvent resulted in 0.04 g (6%) of ethyl 2-acetamido-1-cyclohexene
carboxylate (32): 1H-NMR (CDCl3) δ 1.25 (t, 3H, J ) 7.1 Hz), 1.80
(m, 4H), 1.95 (s, 3H), 2.57 (m, 4H), 4.20 (q, 2H, J ) 7.1 Hz), and
6.35 (br s, 1H, NH); 13C-NMR (CDCl3) δ 14.1, 21.2, 33.5, 37.3, 37,8,
59.9, 129.8 (CdCN), 155.5 (CdCN), 165.8 (CON), and 169.9 (CO2);
m/e 211 (M+), 168, 140, 123 (base), 94, 79, and 43. Anal. Calcd for
C11H17NO3: C, 62.54; H, 8.11; N, 6.63. Found: C, 62.50; H, 8.15; N,
6.65.
combined organic phases were washed with brine and dried over
anhydrous sodium sulfate. After evaporation of the solvent, the residue
(1.65 g) was submitted to flash chromatography on silica gel using a
pentane-ether mixture to give 0.396 g (26%) of the fluoro derivative
1
44: IR (CHCl3) 1720 (CO), 1670 cm-1 (CdC); H-NMR (CDCl3) δ
1.25 (3H, t), 2.45 (3H, d, J ) 21 Hz), 3.75 (2H, d, J ) 3.8 Hz), 4.20
(2H, q), 7.30 (5H, m); m/e 222 (25), 176, 147, 129, and 91; GC purity
g99%. Following elution with the same solvent yielded a mixture
(0.17 g) containing both the fluoro derivatives 44 and 45 [NMR 45:
1H-NMR (CDCl3) δ 1.35 (3H, t), 2.05 (3H, d, J ) 3.8 Hz), 3.55 (2H,
d, J ) 3.8 Hz), 4.30 (2H, q), and 7.25 (5H, m); m/e 222 (37), 177,
149, 129, and 91; GC purity: g99%] together with the phenyl-inserted
derivatives 50 and 51 [compound 50: 1H-NMR (CDCl3) δ 1.12 (3H,
t), 2.10 (3H, s), 3.78 (2H, s), 4.20 (2H, q), 7.40 (10H, m); m/e 280
(73), 234, 206, 191, 155, 129, and 91. Compound 51: 1H-NMR
(CDCl3) δ 1.25 (3H, t), 2.30 (3H, s), 3.55 (2H, s), 4.15 (2H, q), and
7.40 (10H, m); m/e 280 (23), 234, 206, 189, 156, 115, and 91]. Further
elution with pentane containing 5% of ether afforded 0.33 g (24%) of
indene 46: IR (CHCl3) 1705 (CO), 1655 cm-1 (CdC); 1H-NMR (CDCl3
) δ 1.35 (3H, t), 2.53 (3H, m), 3.60 (2H, m), 4.30 (2H, q), and 7.25
(4H, m); m/e 202 (33), 157, 143, and 129. Anal. Calcd for C13H14O2:
C, 77.20; H, 6.98. Found: C, 77.10; H, 7.00. Following elution with
the same solvent yielded an inseparable mixture (0.138 g) of the two
indenes 46 and 47 [indene 47: 1H-NMR (CDCl3 ) δ 1.25 (3H, t), 2.53
(3H, m), 3.55 (2H, m), 4.20 (2H, q), and 7.35 (4H, m); m/e 202 (1),
129, 128, and 91]. Further elution with pentane containing 7% of ether
gave an inseparable mixture (0.23 g, 15%) of the two â-keto-esters 48
and 49 [NMR 48: 1H-NMR (CDCl3 ) δ 1.13 (3H, t), 2.14 (3H, s), 3.09
(1H, d, J ) 6.5 Hz), 3.60 (2H, d, J ) 8.6 Hz), 4.10 (2H, q, J ) 6.5
Hz), and 7.15 (5H, m). NMR 49: 1H-NMR (CDCl3 ) δ 1.14 (3H, t),
1.20 (3H, m), 2.05 (1H, m), 3.80 (2H, s), 4.10 (2H, q, J ) 6.5 Hz),
and 7.15 (5H, m)]. Finally, further elution with pentane containing
10% of ether afforded lactone 52 (0.100 g, 8.4%): 1H-NMR (CDCl3 )
δ 2.15 (3H, m), 5.05 (2H, m), and 7.50 (5H, m); 13C-NMR (75 MHz,
CDCl3) δ 10.4, 70.3, 122.7, 127.1, 129, 130.1, 131.2, 154.8, and 175.3.
Anal. Calcd for C11H10O2: C, 75.84; H, 5.79. Found: C, 75.80; H,
5.80.
Reaction of Ethyl 2-Diazo-2-(1-hydroxycyclobutyl)acetate (36)
with Boron Trifluoride Etherate. Ethyl 2-diazo-2-(1-hydroxycy-
clobutyl)acetate (36) was obtained in 83% yield as a yellow oil by
starting with 0.72 g (10 mmol) of cyclobutanone: IR (neat) 2090, 1682,
1301, and 1118 cm-1; 1H-NMR (300 MHz, CDCl3) δ 1.19 (t, 3H, J )
7.2 Hz), 1.53-1.62 (m, 1H), 1.79-1.87 (m, 1H), 2.18-2.32 (m, 4H),
3.83 (brs, 1H), and 4.14 (q, 2H, J ) 7.2 Hz); 13C-NMR (75 MHz,
CDCl3) δ 12.9, 14.1, 35.1, 60.6, 71.9, and 166.2.
A solution of 0.461 g (2.5 mmol) of 36 in 2.5 mL of benzene was
added dropwise during 30 min to a magnetically stirred solution of
0.46 mL (3.74 mmol) of freshly distilled BF3.Et2O in 2.5 mL of benzene
under nitrogen at 5 °C. Stirring was continued for 2.5 h after which a
saturated NaHCO3 solution was added, and the resulting mixture was
extracted with ethyl acetate. The combined organic phases were washed
with brine and dried over anhydrous MgSO4. Concentration of the
mixture under reduced pressure followed by flash silica gel column
chromatography gave 0.276 g (51%) of ethyl 2-phenylcyclopent-1-
A solution of 1.00 g (4.03 mmol) of 43 in 10 mL of pentane was
added dropwise during 30 min to a magnetically stirred solution of
0.87 mL (6.15 mmol) of freshly distilled BF3‚Et2O in 10 mL of pentane
under nitrogen at 0 °C. Stirring was continued for 10 min after which
a saturated sodium hydrogen carbonate solution was added, and the
resulting mixture was extracted with ethyl acetate. The combined
organic phases were washed with brine and dried over anhydrous
sodium sulfate. After evaporation of the solvent, the residue (0.90 g)
was submitted to flash chromatography on silica gel using a pentane-
ethyl acetate mixture (95:5) to give 0.089 g (10%) of the fluoro
derivative 44 followed by a mixture containing 44 and 45 (0.134 g,
15%). Further elution with pentane containing 10% of ethyl acetate
afforded indene 46 (0.065 g, 8%). Further elution with the same solvent
yielded a mixture containing 46 and 47 (0.212 g, 26%). Further elution
with pentane containing 20% of ethyl acetate gave an inseparable
mixture of â-ketoesters 48 and 49 (0.058 g, 6.6%). Finally, further
elution with pentane containing 30% of ethyl acetate afforded 0.070 g
(10%) of lactone 52.
enecarboxylate (37):65 IR (neat) 1703, 1591, 1114, and 1042 cm-1
;
1H-NMR (300 MHz, CDCl3) δ 1.11 (t, 3H, J ) 7.1 Hz), 1.99 (pent,
2H, J ) 7.6 Hz), 2.85 (m, 4H), 4.08 (q, 2H, J ) 7.1Hz), and 7.31 (m,
5H); 13C-NMR (75 MHz, CDCl3) δ 13.9, 21.9, 35.1, 40.1, 59.9, 127.6,
127.7, 127.8, 129.3, 137.1, 153.0, and 166.3; HRMS calcd for C14H16O2
216.1150, found 216.1164. Compound 37 was closely followed by a
small amount (0.022 g, 5%) of the fluoro derivative 38. Further elution
with the same solvent afforded 0.125 g (32%) of â-ketoester 39 whose
spectral data were identical to that of authentic ethyl 2-oxocyclopen-
tanecarboxylate.
Reaction of 1-(Ethoxycarbonyldiazomethyl)-2-phenylisopropyl
Alcohol (43) with Boron Trifluoride Etherate. A cold (-78 °C)
solution of lithium diisopropylamide [prepared by the addition of
n-butyllithium in hexane (56.0 mL of a 1.0 M solution) to a solution
of diisopropylamine (6.72 g, 66.5 mmol) in THF (30 mL)] was added
during 2 h to a stirred solution of 6.33 g (47.2 mmol) of phenylacetone
and 5.77 g (50.6 mmol) of ethyl diazoacetate at -78 °C under an argon
atmosphere. After the addition was complete, 5 mL of acetic acid in
25 mL of ether at -78 °C was added, and the reaction mixture was
allowed to warm to room temperature. Water was then added, the
organic phase was separated, and the aqueous layer was extracted with
chloroform. The combined organic layer was washed with brine and
dried over anhydrous sodium sulfate. After evaporation of the solvent,
the residue (10.5 g) was chromatographed on alumina (activity IV)
with a pentane-ether mixture to give 9.74 g (83%) of 43: IR (CHCl3)
3445 (OH), 2080 (sCdN), 1655 cm-1 (CO); 1H-NMR (CDCl3) δ
1.20-1.55 (6H, m), 3.10 (2H, s), 3.90 (1H, s), 4.25 (2H, q, J ) 8.5
Hz), and 7.25 (5H, m).
A solution of 1.00 g (4.03 mmol) of 43 in 10 mL of acetonitrile
was added dropwise during 30 min to a magnetically stirred solution
of 0.87 mL (6.15 mmol) of freshly distilled BF3‚Et2O in 10 mL of
acetonitrile under nitrogen at 0 °C. Stirring was continued for 10 min
after which a saturated sodium hydrogen carbonate solution was added
and the resulting mixture was extracted with ethyl acetate. The
combined organic phases were washed with brine and dried over
anhydrous sodium sulfate. After evaporation of the solvent, the residue
(0.90 g) was submitted to flash chromatography on silica gel using a
pentane-ethyl acetate mixture (90:10) to give a mixture of indenes 46
and 47 (0.179 g, 22%). Further elution with pentane containing 20%
of ethyl acetate gave an inseparable mixture of â-ketoesters 48 and 49
(0.177 g, 20%). Finally, further elution with the same solvent afforded
enamide 53 (0.316 g, 30%): 1H-NMR (CDCl3 ) δ 1.25 (3H, t), 1.95
(3H, s), 2.50 (3H, s), 3.72 (2H, s), 4.20 (2H, q), and 7.30 (5H, m).
Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found: C,
68.90; H, 7.30; N, 5.40.
A solution of 1.70 g (6.85 mmol) of 43 in 10 mL of benzene was
added dropwise during 30 min to a magnetically stirred solution of
1.38 mL (11.17 mmol) of freshly distilled BF3‚Et2O in 10 mL of
benzene under nitrogen at 5 °C. Stirring was continued for 10 min
after which a saturated sodium hydrogen carbonate solution was added,
and the resulting mixture was extracted with ethyl acetate. The

12 J. Am. Chem. Soc., Vol. 118, No. 1, 1996
Pellicciari et al.
Reaction of 1-Hydroxy-1-(ethoxycarbonyldiazomethyl)-2,2,6,6-
tetradeuterocyclohexane (84) with Boron Trifluoride Etherate. A
suspension containing 5.68 g (57.9 mmol) of cyclohexanone and 0.60
g of potassium carbonate in 90 mL of deuterium oxide was heated at
reflux for 62 h. After cooling, the reaction mixture was extracted with
ether, and the combined organic phase was concentrated under reduced
pressure. The residue (6 g) was distilled to give 5.6 g (95%) of 2,2,6,6-
tetradeuterated cyclohexanone: bp 154-6 °C; 1H-NMR (CDCl3) δ 1.80
(6H, m).
64a-c were thus submitted to G-92 with initial θ(CdC+C(CO))’s
around 120°. Similarly, the cyclic vinyl cations 65a-c were input to
the ab initio calculation with ring geometries very similar to that found
in cycloheptene and cyclohexene, respectively. Furthermore, the
carbonyl of the ester group was positioned syn to the vinyl cation center.
Distortion from neutral hydrocarbon geometries as listed in Table 1
are a direct result of the gas phase 6-31G* optimization. Allyl cations
66a-c were treated similarly, the CH2+CdC moiety introduced as a
planar fragment and the ester CdO oriented syn to the exocyclic CH2
group.
The simpler structures 67-69 were geometry optimized by employ-
ing Z-matrix input. Transition states 70q and 71q sustain a single
negative eigenvalue after geometric refinement. Structures 79-77q
carrying a molecule of dimethyl ether (Table 2) were treated similarly.
All final refined G-92 structures were subjected to coordinate conversion
and viewed in 3-D with Sybyl software.68
A cold (-78 °C) solution of lithium diisopropylamide [prepared from
the addition of 16.65 mL of a 1.18 M hexane solution of n-butyllithium
to 2.23 g (22.0 mmol) of a solution of diisopropylamine in 20 mL of
THF] was added during 40 min to a stirred solution of 1.76 g (17.2
mmol) of the above tetradeuterated cyclohexanone and 2.04 g (17.9
mmol) of ethyl diazoacetate at -78 °C under a nitrogen atmosphere.
After the addition was complete, 1 mL of acetic acid in 20 mL of ether
at -78 °C was added, and the reaction mixture was allowed to warm
to room temperature. Water was added, the organic phase was
separated, and the aqueous layer was extracted with chloroform. The
combined organic phase was washed with brine and dried over
anhydrous sodium sulfate. After evaporation of the solvent, the residue
(4.3 g) was chromatographed on alumina (activity IV) eluting with
pentane-ether to give 2.67 g (72%) of 84: IR (CHCl3) 2045 (CdN2),
Acknowledgment. A.P. gratefully acknowledges support of
this work by the National Science Foundation. B.L.W. is
pleased to acknowledge the NIH for a postdoctoral fellowship
(GM-16184-01). Use of the high-field NMR spectrometer used
in these studies was made possible through equipment grants
from the NIH and NSF.
1
1665 cm-1 (CO); H-NMR (CDCl3) δ 1.31 (3H, t, J ) 7 Hz), 1.43-
2.00 (6H, m), 3.60 (1H, m), 4.20 (2H, q, J ) 7 Hz).
Supporting Information Available: Tables of 6-31G*
relative energies for V1, V2, and A1 with optimized geometries
for dimethyl ether solvated carbocations as well as supplemental
experimental for the preparation of esters 26, 35, 37 and 42 (4
pages). This material is contained in many libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, can be ordered from the ACS, and can
be downloaded from the Internet; see any current masthead page
for ordering information and Internet access instructions.
A solution of 0.88 g (4.07 mmol) of 84 in 8 mL of benzene was
added dropwise over a 10 min period to a solution of 0.75 mL (6.1
mmol) of BF3‚OEt2 in 10 mL of benzene kept under vigorous magnetic
stirring at 5 °C under a nitrogen atmosphere. After the addition was
complete, the reaction mixture was allowed to warm to room temper-
ature and was then concentrated in Vacuo. The residue (0.5 g) was
submitted to flash silica gel chromatography using a pentane-ether
mixture. The major fraction contained 0.35 g (35%) of ethyl 2-phe-
nyldideuteromethyl-6,6-dideuterocyclohexenecarboxylate (85): IR
(CHCl3) 1695 cm-1 (CO); 1H-NMR (CDCl3) δ 1.25 (3H, t, J ) 7 Hz),
1.58 (4H, m), 2.02 (2H, m), 4.22 (2H, q, J ) 7 Hz), 7.27 (5H, m).
Computational Results. The methyl esters of 64-66 were con-
structed in MacroModel66 as their neutral hydrides and optimized with
the MM2 force field. The appropriate H- was removed, and the
corresponding carbocation was subsequently optimized with the 6-31G*
basis set over cartesian coordinates in Gaussian-92.67 Vinyl cations
JA950971S
(67) Frisch, M. J.; Trucks, G. W.; Head-Gordon, M.; Gill, P. M. W.;
Wong, M. W.; Foresman, J. B.; Johnson, B. G.; Schlegel, H. B.; Robb, M.
A.; Replogle, E. S.; Gomperts, R.; Andres, J. L.; Raghavachari, K.; Binkley,
J. S.; Gonzalez, C.; Martin, R. L.; Fox, D. J.; Defrees, D. J.; Baker, J.;
Stewart, J. J. P.; Pople, J. A. Gaussian 92, Revision A; Gaussian Inc.:
Pittsburgh, PA, 1992.
(66) Macromodel, Version 4.5, C. Still, Department of Chemistry,
Columbia University, New York, NY, 10027.
(68) Sybyl Molecular Modeling Software, Version 6.0; Tripos Associates
Inc.: 1699 S. Hanley Rd., St. Louis, MO, 63144-2913.