Sequential cyclization/silylation of enynes catalyzed by an organoyttrium complex

Article abstract of DOI:10.1021/ja971538g

The organoyttrium complex Cp*₂YCH₃·THF (Cp* = C₅Me₅) has been shown to be an effective precatalyst for the selective sequential cyclization/silylation of 1,6- and 1,7-enynes. The catalyst's ability to insert the

Full text of DOI:10.1021/ja971538g

J. Am. Chem. Soc. 1997, 119, 8817-8825
8817
Sequential Cyclization/Silylation of Enynes Catalyzed by an
Organoyttrium Complex
Gary A. Molander* and William H. Retsch
Contribution from the Department of Chemistry and Biochemistry, UniVersity of Colorado,
Boulder, Colorado 80309-0215
ReceiVed May 12, 1997X
Abstract: The organoyttrium complex Cp*2YCH3‚THF (Cp* ) C5Me5) has been shown to be an effective precatalyst
for the selective sequential cyclization/silylation of 1,6- and 1,7-enynes. The catalyst’s ability to insert the alkyne
in preference to the alkene in a regioselective manner, combined with the high diastereoselectivity of the insertion
process, yields a product with only one stereochemistry about the exocyclic olefin. The reaction proceeds under
extremely mild conditions with short reaction times. Cyclization of enynes functionalized in the allylic position
affords silylated carbocycles with high diastereoselectivities and excellent yields.
Introduction
The combination of these reports prompted us to investigate
the extension of this chemistry to cyclization/silylation reactions
of enynes. The focus of these efforts was to establish a protocol
for this transformation utilizing a highly selective organoyttrium
catalyst. Catalytic enyne cyclizations have been accomplished
using a variety of palladium complexes and have provided a
vast array of useful products, including intermediates in a
number of natural product syntheses.4 Intramolecular Pauson-
Khand cyclizations of enynes make up a large class of processes
that generate bicyclic cyclopentenones from acyclic enyne
starting materials.5 A number of stoichiometric as well as more
recently reported catalytic protocols employ a variety of metal
complexes to effect this transformation.5b-g Zirconium metal-
locene complexes have been utilized with enynes to mediate
the formation of metallocycle intermediates that can be carried
on to a Pauson-Khand-type product when reacted with carbon
monoxide or protonated to yield a carbocyclic product.6
The process that we envisioned for the organoyttrium-
catalyzed cyclization/silylation of enynes would be comple-
mentary to the previously reported methods. A viable catalytic
cycle, similar to that proposed for the cyclization/silylation of
dienes,1g is outlined in Scheme 1. At the outset, there were
unknowns in several key steps of the process, and the success
or failure of the sequence could only be determined effectively
by experiment. The catalytic cycle would be initiated by a
The use of organolanthanide and group 3 and 4 organome-
tallic complexes as hydrosilylation catalysts of alkenes and
dienes has been well established,1 but the reactivity of silanes
with enynes and other polyunsaturated systems in the presence
of these various catalysts has been relatively unexplored.2 Initial
reports that organolanthanides could catalyze the regioselective
hydrosilylation of terminal alkenes were soon followed by
accounts of chemoselective reactions of dienes that utilized
similar but more reactive organoyttrium complexes.1c,d Previous
investigations have demonstrated that internal alkynes can also
be catalytically hydrosilylated using an organoyttrium catalyst
to prepare (E)-alkenylsilanes in a regioselective and stereose-
lective manner.2a
Organoyttrium and related catalysts have been utilized for
selective carbon-carbon bond formation as well.1e-i,3 Catalytic
cyclizations of simple dienes using a variety of lanthanide and
group 3 and group 4 metallocene complexes have demonstrated
the ability to generate carbocycles through intramolecular
insertion of a terminal olefin in conjunction with a variety of
termination steps.1e-i,3 Examples of previously reported cy-
clization reactions of dienes have taken advantage of the
chemoselectivity of organoyttrium catalysts to cyclize substituted
dienes selectively.1e,g,i The integration of a silylation in the
termination step of this reaction provides additional functionality
in the carbocyclic product.
(4) (a) For a review see: Trost, B. M. Acc. Chem. Res. 1990, 23, 34 and
references therein. (b) Trost, B. M.; Lautens, M.; Chan, C.; Jeberatnam, D.
J.; Mueller, T. J. Am. Chem. Soc. 1992, 113, 636. (c) Villa, M.; Dumas, J.;
Trost, B. M. J. Am. Chem. Soc. 1992, 114, 9836. (d) Trost, B. M.; Dumas,
J. J. Am. Chem. Soc. 1992, 114, 1924. (e) Chang, V. K.; Trost, B. M.
Synthesis 1993, 825. (f) Phan, L. T.; Trost, B. M. Tetrahedron Lett. 1993,
34, 4735. (g) Zhu, G.; Lu, X. J. Org. Chem. 1995, 60, 1087. (h) Ji, J.;
Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 1160. (i) Ji, J.; Wang, Z.; Lu,
X. Organometallics 1996, 15, 2821. (j) Trost, B. M.; Fleitz, F. J.; Watkins,
W. J. J. Am. Chem. Soc. 1996, 118, 5146.
(5) (a) For a general review see: Schore, N. E. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 5, pp 1037-1064. (b) For a review of transition metal-catalyzed
reactions see: Catellani, M.; Chivsoli, G. P.; Costa, M. J. Organomet. Chem.
1995, 500, 69. (c) Livinghouse, T.; Pagenkopf, B. L. J. Am. Chem. Soc.
1996, 118, 2285. (d) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J.
Am. Chem. Soc. 1996, 118, 9450. (e) Hicks, F. A.; Buchwald, S. L. J. Am.
Chem. Soc. 1996, 118, 11688. (f) Hicks, F. A.; Berk, S. C.; Buchwald, S.
L. J. Org. Chem. 1996, 61, 2713. (g) Zhang, M.; Buchwald, S. L. J. Org.
Chem. 1996, 61, 4498.
X Abstract published in AdVance ACS Abstracts, September 1, 1997.
(1) (a) Sakakura, T.; Lautenschlager, H.-J.; Tanaka, M. J. Chem. Soc.,
Chem. Commun. 1991, 40. (b) Kesti, M. R.; Waymouth, R. M. Organo-
metallics 1992, 11, 1095. (c) Molander, G. A.; Julius, M. J. Org. Chem.
1992, 57, 6347. (d) Molander, G. A.; Hoberg, J. O. J. Org. Chem. 1992,
57, 3266. (e) Molander, G. A.; Hoberg, J. O. J. Am. Chem. Soc. 1992, 114,
3123. (f) Sakakura, T.; Tanaka, M.; Onozawa, S. Tetrahedron Lett. 1994,
35, 8177. (g) Molander, G. A.; Nichols, P. J. J. Am. Chem. Soc. 1995, 117,
4415. (h) Marks, T. J.; Fu, P.-F.; Brard, L.; Li, Y. J. Am. Chem. Soc. 1995,
117, 7157. (i) Molander, G. A.; Nichols, P. J. J. Org. Chem. 1996, 61,
6040. (j) Molander, G. A.; Winterfeld, J. J. Organomet. Chem. 1996, 524,
275.
(2) (a) Molander, G. A.; Retsch, W. H. Organometallics 1995, 14, 4570.
(b) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1996, 118, 707. (c) Heeres, H.
J.; Heeres, A.; Teuben, J. H. Organometallics 1990, 9, 1508.
(3) (a) Bunel, E.; Burger, B. J.; Bercaw, J. E. J. Am. Chem. Soc. 1988,
110, 976. (b) Resconi, L.; Waymouth, R. M. J. Am. Chem. Soc. 1990, 112,
4953. (c) Piers, W. E.; Bercaw, J. E. J. Am. Chem. Soc. 1990, 112, 9406.
(d) Piers, W. E.; Shapiro, P. J.; Bunel, E. E.; Bercaw, J. E. Synlett 1990,
74. (e) Coates, G. W.; Waymouth, R. M. J. Am. Chem. Soc. 1991, 113,
6270. (f) Kesti, M. R.; Waymouth, R. M. J. Am. Chem. Soc. 1990, 112,
4953. (g) Shaughnessy, K. H.; Waymouth, R. M. J. Am. Chem. Soc. 1992,
114, 3563. (h) Knight, K. S.; Waymouth, R. M. Chemtech 1995, 25, 15.
(6) (a) For reviews see: Negishi, E.-i. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
5, pp 1163-1184. (b) Negishi, E.-i.; Takahashi, T. Acc. Chem. Res. 1994,
27, 124. (c) Pagenkopf, B. L.; Lund, E. C.; Livinghouse, T. Tetrahedron
1995, 51, 4421.
S0002-7863(97)01538-2 CCC: $14.00 © 1997 American Chemical Society

8818 J. Am. Chem. Soc., Vol. 119, No. 38, 1997
Molander and Retsch
Scheme 1
Scheme 2
Scheme 3
σ-bond metathesis between Cp*2YCH3‚THF and PhSiH3, pro-
ducing a catalytically active metal hydride species.1c-e,g,i,2a Next,
the catalyst would have to insert one of the two sites of
unsaturation of the enyne preferentially. Although evidence
supported the proposition that the alkyne would be more
reactive,7 the extent to which selectivity could be achieved
remained to be tested. If adequate chemoselectivity for the
alkyne could be achieved, it was known that regioselectivity in
this process could be dictated by steric effects to form a single
alkenylyttrium intermediate.2a This intermediate, known to react
through a σ-bond metathesis with phenylsilane to yield an
alkenylsilane,2a might also undergo cyclization via an intramo-
lecular olefin insertion. The intramolecular insertion of an
alkene into a lanthanide sp2 carbon bond has little precedent,2b,c
and whether or not the insertion would occur in preference to
direct σ-bond metathesis with phenylsilane was entirely un-
known. Cyclization, if favored, would produce a second
intermediate alkylyttrium species. This second intermediate,
similar to those proposed in diene cyclizations,1e-i would be
expected to undergo a subsequent σ-bond metathesis with silane
to generate the desired product. All of these steps would have
to be accomplished selectively in order to cyclize even a simple
enyne, but to be truly useful a catalyst would also be required
to react under mild conditions, at a reasonable rate, and tolerate
a variety of functional groups as well.
Scheme 4
ylsilyl ether in high yield.8a The cyclohexyl substituent was
placed on the alkyne according to published procedures to afford
1a.9 Removal of the silyl protecting group with TBAF followed
by oxidation via a modified Swern procedure afforded 3a.10
Vinylmagnesium bromide addition to the aldehyde of 3a
provided the desired allylic alcohol 4a. The allylic alcohol was
then protected according to published procedures to yield the
desired substrates.8 The tertiary amine of 26 was accessed via
a Mitsunobu coupling of 4a with phthalimide11 followed by
complete reduction of the carbonyl functionalities with LAH
to afford 26.12
We now report that the organoyttrium hydride catalyst derived
from Cp*2YCH3‚THF (Cp* ) C5Me5) is indeed an effective
catalyst for the selective cyclization of 1,6- and 1,7-enynes in
the postulated manner, providing facile access to highly func-
tionalized carbocycles.
Results and Discussion
A series of 1,6-enyne substrates designed to test this new
protocol was prepared according to Schemes 2-4. The
substrates 20, 22, 24, and 26 were all derived from 4a. Scheme
2 outlines the synthesis of this intermediate. Commercially
available 4-pentyn-1-ol was protected as the tert-butyldimeth-
(8) (a) Corey, E. J.; Venkatesvarlu, A. J. Am. Chem. Soc. 1972, 94, 6190.
(b) Corey, E. J.; Cho, H.; Ru¨cker, C.; Hua, D. H. Tetrahedron Lett. 1981,
22, 3455. (c) Miyashita, M.; Yoshikoshi, A. J. Org. Chem. 1977, 42, 3772.
(d) Colin-Messager, C.; Girard, J.-P.; Rossi, J.-C. Tetrahedron Lett. 1992,
33, 2689.
(9) Brown, H. C.; Sinclair, J. A.; Midland, M. M. J. Am. Chem. Soc.
1973, 95, 3080.
(10) Wipf, P.; Fritch, P. C. J. Org. Chem. 1994, 59, 4875.
(11) Mulzer, J.; Brand, C. Tetrahedron 1986, 42, 5961.
(12) Iriuchijima, S. Synthesis 1978, 684.
(7) (a) Evans, W. J.; Meadows, J. H.; Hunter, W. E.; Atwood, J. L. J.
Am. Chem. Soc. 1984, 106, 1291. (b) Jeske, G.; Lauke, H.; Mauermann,
H.; Schumann, H.; Marks, T. J. J. Am. Chem. Soc. 1985, 107, 8111. (c)
Jeske, G.; Lauke, H.; Mauermann, H.; Swepston, P. N.; Schumann, H.;
Marks, T. J. J. Am. Chem. Soc. 1985, 107, 8091. (d) Jeske, G.; Schock, L.
E.; Swepston, P. N.; Schumann, H.; Marks, T. J. J. Am. Chem. Soc. 1985,
107, 8103.

Sequential Cyclization/Silylation of Enynes
J. Am. Chem. Soc., Vol. 119, No. 38, 1997 8819
The synthesis of substrates 6, 7, 8, and 10 is shown in Scheme
3. The aldehyde 3b was prepared similarly to 3a and then
treated with N,N-dimethylhydrazine to form hydrazone 5.
Treatment of hydrazone 5 with LDA and alkylation with the
appropriate electrophile was followed by removal of the
hydrazone with wet Amberlyst. The resultant aldehydes were
subjected directly to a Wittig reaction to yield the desired
substituted enynes.13 Some of compound 8 was used as a
substrate, while a portion was treated with TMSI, cleaving the
methyl ether to yield alcohol 9.14 Protection of 9 as the tert-
butyldimethylsilyl ether afforded substrate 10. Aldehyde 3b
was also subjected directly to a Wittig reaction for the
preparation of 16 in 86% yield.
that the protected alcohol adequately hindered initial insertion
of the alkene without compromising the intramolecular insertion
required to form the cyclized products.
The formation of a new stereocenter in the cyclization reaction
of 20 results in two diastereomeric products, 21a and 21b. The
ratio of products as determined by fused silica gas chromato-
graphic analysis was 6.5:1. The relative stereochemistry of the
major product of the reaction was determined to be trans with
respect to the ring substituents from the X-ray crystal structure
of diol 36 obtained from the one-step oxidation/deprotection
of 21a (eq 1).19 The origin of the diastereoselectivity observed
Substrates 32 and 34 were prepared by alkylation of the
appropriate terminal alkyne with bromide 15. The preparation
of 15 is outlined in Scheme 4. Aldehyde 11 was prepared
according to the literature procedure15 and treated with vinyl-
magnesium bromide to provide allylic alcohol 12. The allylic
alcohol of 12 was protected as the trityl ether to provide 13.
Selective deprotection using TBAF afforded the primary alcohol
14. Treatment with dibromotriphenylphosphorane yielded the
desired bromide 15.16 2,2-Dimethyl-5-ethynyl-1,3-dioxane was
prepared from the literature procedure,17 treated with n-BuLi
to prepare the lithium acetylide, and alkylated with 15 to afford
substrate 34. Similarly, commercially available (()-3-butyn-
2-ol was protected as the tert-butyldimethylsilyl ether and
alkylated with bromide 15 to yield substrate 32. Substrate 18
was prepared from the lithium acetylide of commercially
available 3-methyl-1-pentyne and 5-bromo-1-pentene in 75%
yield.
With the substrates in hand, investigations were undertaken
to determine optimum reaction conditions for the cyclization/
silylation reactions and to outline the scope and limitations of
the process. Compound 16 was utilized as the archetypal
substrate for these studies (Table 1). The cyclization/silylation
reaction of this substrate was carried out with 5 mol % of the
precatalyst in the presence of an excess of phenylsilane at 25
°C for 2 h (entry 1). Compounds 17a and 17b were both
produced in the reaction. The major cyclized product 17a was
obtained in 60% isolated yield and was formed by preferential
insertion of the alkyne into the catalyst. The minor product,
17b, was formed by initial insertion of the alkene. The latter
process forms an intermediate alkylyttrium species that under-
goes σ-bond metathesis with phenylsilane to form a second
intermediate, 1-cyclohexyl-7-(phenylsilyl)-1-heptyne.18 This is
transformed by another hydrosilylation reaction at the alkyne,
ultimately forming 17b.
in the cyclization can be explained by the transition structure
pictured in Scheme 1. If the alkenylmetallic intermediate
produced by insertion of the alkyne adopts a chairlike transition
structure, the allylic substituent should occupy a pseudoequa-
torial position about the newly forming ring. This transition
structure predicts the configuration of the major cyclized product
to be trans with respect to the ring substituentssthe same as
the configuration of the major product 21a.
Some improvement in the diastereoselectivity was achieved
when larger alkoxy groups were incorporated in the starting
materials as depicted in entries 4 and 5. This provides further
evidence for the transition structure suggested in Scheme 1
because the improved diastereomeric ratio of the products can
be attributed to the bulkier allylic substituents having an
increased preference to assume a pseudoequatorial orientation.
Improvement of the diastereoselectivity of the reaction was also
attempted by performing the reaction of 20 at 0 and -20 °C.20
The decrease in reaction temperature had no effect on the
observed diastereomeric ratio.21 A complex incorporating a
lanthanide metal with a smaller ionic radius was also utilized
in an effort to improve the diastereoselectivity of the reaction.
It was reasoned that if the orientation of the allylic substituent
in the transition state was affected by the bulky Cp* ligands of
the complex, then a smaller metal could allow for the formation
of a tighter coordination environment and increase the preference
for a pseudoequatorial orientation of the substituent. Thus,
Cp*2LuCH3‚THF was prepared and utilized as the precatalyst
in the reaction of 20 and 22. This precatalyst had a reactivity
similar to the yttrium complex, but did not alter the observed
diastereomeric ratios of the products.
The diastereoselectivities of the cyclization reactions were
exceedingly high when allylic substituents with A values greater
than that of a protected alcohol were incorporated into the enyne
substrates. The tertiary amine substituent of 26 provided
products in high yields and with excellent diastereoselectivity
(40:1). Oxidation of the silane in this series would provide
access to interesting â-amino alcohol derivatives. When alkyl
substituents were incorporated in substrates 6 and 7, formation
of the minor diastereomer was not observed. Similarly, 10
reacted to give only the major diastereomer cleanly and in good
yield. Substrate 8 differs from 10 only with respect to the
protecting group on the primary alcohol, but was unreactive
with the catalyst at 25 and 50 °C. This result was not entirely
unexpected because methoxy groups have been known to inhibit
In order to increase selectivity for the formation of the
cyclized product, the catalyst’s preference for initial insertion
of the alkyne over the alkene was improved. The addition of
a (tert-butyldimethylsilyl)oxy substituent in the allylic position
of 20 was expected to favor the insertion of the alkyne by
lowering the reactivity of the alkene by both steric and electronic
effects.1c The reaction of substrate 20 demonstrated that higher
yields of cyclized products could be obtained with no formation
of uncyclized hydrosilylated products (entry 3). This suggested
(13) Fitjer, L.; Quabek, U. Synth. Commun. 1985, 15, 855.
(14) Jung, M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761.
(15) Hall, D. G.; Caille, A.-S.; Drouin, M.; Lamothe, S.; Mueller, R.;
Deslongchamps, P. Synthesis 1995, 9, 1081.
(16) (a) Wiley, G. A.; Hershkowitz, R. L.; Rein, B. M.; Chung, B. C. J.
Am. Chem. Soc. 1964, 86, 964. (b) Borch, R. F.; Evans, A. J.; Wade, J. J.
J. Am. Chem. Soc. 1977, 99, 1612.
(17) Bates, A. H.; Farina, J.; Tong, M. J. Org. Chem. 1986, 51, 2637.
(18) This compound was identified as the intermediate observed in the
reaction of 16 to 17a and 17b from a comparison of retention times using
fused silica gas chromatographic analysis. Full characterization can be found
in the experimental as compound 17c.
(19) Smitrovich, J. H.; Woerpel, K. A. J. Org. Chem. 1996, 61, 6044.
(20) Cyclopentane was used as the solvent for low-temperature reactions.
(21) Diastereomeric ratios were determined by fused silica gas chro-
matographic analysis.

8820 J. Am. Chem. Soc., Vol. 119, No. 38, 1997
Molander and Retsch
Table 1. Cyclization/Silylation of Enynes Catalyzed by Cp*2YCH3‚THFa
the reactivity of organolanthanide catalysts.1j After initial
insertion of the alkyne of substrate 8 into the catalyst, a seven-
membered ring chelate can form that apparently renders the
catalyst unreactive until the reaction is heated to 100 °C.
Presumably, at this temperature the equilibrium concentration
of ligand-free organometallic is high enough that a reasonable
turnover can be achieved. At this elevated reaction temperature
some loss of diastereoselectivity in the cyclization was observed.
The substrates depicted in entries 1-10 possess a cyclohexyl
or sec-butyl group as a substituent on the alkyne to provide
branching in the propargyl position. This branching serves as
a regiocontrol element and is required to attain complete
regioselectivity in the initial alkyne insertion.2a Entries 11 and
12 provide examples of branched alkyne substituents containing
functionalized groups that can be utilized as substituents on the
alkyne without hindering reactivity. Although the addition of
an allylic alkoxy group in the enyne cyclization inhibited the
initial insertion of the alkene, the protected propargyl alcohol
of substrate 32 had little if any effect on the alkyne in the desired
transformation. Similarly, the oxygens of the acetonide-
protected diol substituent of substrate 34 did not appreciably
affect the reactivity of the highly electron deficient catalyst. The
reaction proceeded readily at room temperature, complete
selectivity in the alkyne insertion was observed, and the cyclized
product was obtained in high yield and with excellent diaste-
reoselectivity.
It was expected that the cyclization/silylation reaction of
enynes could be readily extended to include the formation of
six-membered rings. The reactions of 37 with various silanes
were carried out with this expectation and the results are outlined
in Table 2. Under conditions identical to those that allowed
the cyclization/silylation of 20 to occur, 37 was reacted with
the precatalyst and phenylsilane. No cyclization product was
observed. Instead, the alkyne was hydrosilylated to form 38
cleanly and in high yield. This result again demonstrated the
preference of the catalyst for the initial insertion of an alkyne
over the terminal alkene of a protected allylic alcohol. It also
demonstrated that the alkenylmetallic species produced by the
initial insertion of the alkyne undergoes σ-bond metathesis with
phenylsilane more readily than an intramolecular insertion of

Sequential Cyclization/Silylation of Enynes
J. Am. Chem. Soc., Vol. 119, No. 38, 1997 8821
Table 2. Effect of the Silane on the Formation of a Six-Membered Ringa
Scheme 5
the two steps (Scheme 5). Analysis of the crude reaction
mixture by 1H NMR indicated that a 4:1 diastereomeric mixture
of products was formed. A determination of the relative
stereochemistry of the diastereomers was based on the chemical
shift of the proton on the carbon bearing the hydroxyl group
and its vicinal coupling constant to the proton adjacent to the
methyl group. The appropriate chemical shifts and coupling
constants are shown in Scheme 5 and are consistent with
accepted values for substituted cyclohexyl systems.22 The
relative stereochemistry of the product of entry 2 and the
stereochemistry of the major product derived from entry 3 are
consistent in suggesting that the major product of the cyclization
of an enyne to form a six-membered ring places the ring
substituents trans to one another.
Although methylphenylsilane allowed the formation of a six-
membered ring in preference to the hydrosilylation of the alkyne,
it also created more difficulties in the characterization of the
reaction products because of the addition of a third stereocenter
at silicon. In an effort to avoid the formation of an additional
stereocenter both diphenylsilane and diethylsilane were utilized
in reactions with 37. Neither of these silanes showed any
reactivity with this substrate at temperatures between 25 and
100 °C.
the alkene to form a six-membered ring. This suggested that if
the σ-bond metathesis with the silane could be slowed down,
the intramolecular insertion would occur preferentially to form
a cyclized product. This was accomplished by utilizing different
substituents or more than one substituent on the silane. In entry
2 hexylsilane was utilized as the silylating reagent. This
terminator allowed the six-membered ring to form and to be
isolated as a single diastereomer, but only in moderate yield.
The minor diastereomer that was expected to have formed was
inseparable and unidentifiable in the mixture of other isomers
that were formed in the reaction. The relative stereochemistry
of the isolated diastereomer was determined by X-ray crystal-
lography of diol 41 obtained from the oxidation/deprotection
of 39. In entry 3 methylphenylsilane was utilized and was
shown to provide the cyclized products in high yield. The
formation of the additional stereocenter at silicon made char-
acterization of the reaction products problematic. The crude
reaction mixture could be deprotected and desilylated in one
step to yield a mixture of 42 and 43 in 84% overall yield for
Conclusions
The organoyttrium complex Cp*2YCH3‚THF can be used to
catalyze the cyclization/silylation of suitable 1,6-enynes with
phenylsilane to form functionalized carbocycles diastereoselec-
(22) Spectral Data for Structure Determination of Organic Compounds;
Boschke, F. L., Fresnius, W., Huber, J. F. K., Pungor, E., Rechnitz, G. A.,
Simon, W., West, T. S., Eds.; Springer-Verlag: Berlin, 1983; pp H185 and
H195.

8822 J. Am. Chem. Soc., Vol. 119, No. 38, 1997
Molander and Retsch
1H), 1.98-2.07 (m, 1H), 2.16-2.33 (m, 2H), 2.38-2.46 (m, 1H), 4.28-
tively in a single step. In the sequential process, both a carbon-
carbon and a carbon-silicon bond are formed selectively. The
catalyst accomplishes this reaction through its ability to insert
an alkyne regioselectively in preference to an alkene, proceed
through an intramolecular olefin insertion that engenders high
diastereoselectivity, and finally regenerate the active catalyst
while at the same time placing a functional group on the product.
The diastereoselectivity of the reaction can be enhanced by
increasing the size of allylic substituents on the substrate. It
has also been demonstrated that with an appropriate silane, a
1,7-enyne can be cyclized to provide a six-membered ring
product selectively. In addition to the catalyst’s ability to react
selectively with the substrates, these reactions proceed at very
reasonable rates under extremely mild conditions, and a variety
of functional groups can be tolerated. The method complements
other catalyzed cyclization reactions of enynes, and does so in
a manner that is atom economical, with no byproducts formed
whatsoever in the process.23
1
29
4.34 (m, J
) 192.5 Hz, 2H), 5.02 (br dd, J ) 8.8, 2.1 Hz, 1H),
Si,H
7.32-7.37 (m, 3H), 7.56-7.58 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 15.09, 23.97, 26.12, 26.15, 26.20, 28.43, 33.12, 33.15, 34.74, 38.52,
40.78, 126.12, 127.94, 129.42, 133.10, 135.21, 145.79; IR (neat) 2132.8
cm-1; HRMS calcd for C19H28Si 284.1960, found 284.1955; LRMS
(EI) m/z (relative intensity) 284 (26), 206 (44), 173 (47), 123 (87),
107 (100).
(1E)-1-Cyclohexyl-2,7-bis(phenylsilyl)-1-heptene (17b). Purifica-
tion by flash chromatography in hexanes of the crude mixture of 17a
and 17b followed by Kugelrohr distillation afforded 25% of the minor
product 17b (>99% pure by GC analysis): ot 115-125 °C/0.04 mmHg;
Rf 0.29 (hexanes); 1H NMR (400 MHz, CDCl3) δ 0.85-0.91 (m, 2H),
1.11-1.44 (m, 11H), 1.59-1.75 (m, 5H), 2.15-2.18 (m, 2H), 2.36-
1
29
2.43 (m, 1H), 4.28 (t, J ) 3.5 Hz, J
) 192.2 Hz, 2H), 4.28 (s,
Si,H
1
29
J
Si,H ) 194.4 Hz, 2H), 4.52 (d, J ) 9.1 Hz, 1H), 7.32-7.42 (m, 6H),
7.55-7.57 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 9.87, 24.79, 25.83,
25.99, 29.40, 30.24, 32.68, 32.84, 37.68, 127.88, 127.94, 129.44, 129.47,
131.57, 132.71, 132.74, 135.18, 135.49, 152.00; IR (neat) 2130.8 cm-1
;
HRMS calcd for C25H36Si2 392.2356, found 392.2329; LRMS (EI) m/z
(relative intensity): 313 (26), 285 (32), 107 (100).
Experimental Section
1-Cyclohexyl-7-(phenylsilyl)-1-heptyne (17c). The reaction of 16
was carried out a second time according to the general experimental
procedure except only 0.8 equiv of PhSiH3 were used and the reaction
was quenched 1 min after the addition of PhSiH3. Analysis of the
crude reaction mixture by gas chromatography confirmed that a mixture
of starting material, 17a, 17b, and the intermediate 17c was obtained.
Purification by flash chromatography using 8% CH2Cl2 in hexanes
followed by Kugelrohr distillation afforded 17c cleanly for characteriza-
tion (>97% pure by GC analysis): ot 85-95 °C/0.04 mmHg; Rf 0.29
All operations involving the organoyttrium complex were performed
with rigorous exclusion of oxygen and moisture in flamed Schlenk-
type glassware on an argon line connected to a vacuum system (<0.04
mmHg) or in a nitrogen-filled, Vacuum Atmospheres glovebox. The
cyclohexane and benzene-d6 used as solvents for the reactions were
distilled from Na/benzophenone under argon and then stored in the
glovebox. In preparation for use with the catalyst, substrates were
distilled onto activated 4 Å molecular sieves and freeze/pump/thaw
degassed or dried as a solution with MgSO4, concentrated in vacuo,
and degassed. 5-Hexyn-1-ol, 4-pentyn-1-ol, and 3-methyl-1-pentyne
were purchased from Farchan Laboratories, Inc. The phenylsilane was
purchased from Aldrich. Methylphenylsilane, hexylsilane, diethylsilane,
and diphenylsilane were purchased from Hu¨ls America Inc. All silanes
were dried with activated 4 Å molecular sieves and degassed before
use. Anhydrous YCl3 and LuCl3 were purchased from Cerac. The
complexes Cp*2YCH3‚THF and Cp*2LuCH3‚THF were prepared ac-
cording to published procedures for the yttrium complex.24
General Experimental Procedure for Cyclization/Silylation. The
catalytic cyclization/silylation of 20 is representative. In the nitrogen
atmosphere glovebox a solution of 0.004 g (0.009 mmol) of the pre-
catalyst Cp*2YCH3‚THF in 1 mL of cyclohexane was added to a reac-
tion flask equipped with a magnetic stir bar. To this solution 0.050 g
(0.163 mmol) of 20 was added followed by 0.021 g (0.194 mmol) of
phenylsilane. The reaction flask was sealed and stirred in the glovebox
for 2 h at ambient temperature. After 2 h the reaction mixture was
removed from the glovebox, diluted with 1 mL of Et2O, and filtered
through a 0.5 g column of Florisil. The Florisil was rinsed two times
with 2 mL portions of Et2O. Analysis of the crude reaction mixture
by gas chromatography indicated that a 6.5:1 ratio of diastereomers
was generated. The organics were combined and concentrated by rotary
evaporation. The crude material was purified by flash chromatography
using 6% CH2Cl2 in hexanes followed by Kugelrohr distillation at
reduced pressure to afford 80% (0.054 g, 0.130 mmol) of 21a, the major
trans product, and 13% (0.009 g, 0.022 mmol) of 21b, the minor cis
product.
1
(8% CH2Cl2 in hexanes); H NMR (400 MHz, CDCl3) δ 0.90-0.95
(m, 2H), 1.20-1.52 (m, 12H), 1.63-1.76 (m, 4H), 2.10-2.14 (m, 2H),
1
29
2.26-2.33 (m, 1H), 4.27 (t, J ) 3.8 Hz, J Si,H ) 192.0 Hz, 2H), 7.32-
7.40 (m, 3H), 7.54-7.56 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
9.95, 18.62, 24.61, 24.96, 25.95, 28.80, 29.15, 31.93, 33.17, 79.90,
84.74, 127.94, 129.48, 132.67, 135.19; IR (neat) 2132.6 cm-1; HRMS
calcd for C19H28Si 284.1960, found 284.1959; LRMS (EI) m/z (relative
intensity): 284 (3), 201 (18), 121 (35), 107 (100).
(1E,2R*,2′R*/S*)-1-(2′-Methylbutylene)-2-[(phenylsilyl)methyl]-
cyclopentane (19). Prepared from 18 according to the general experi-
mental procedure. Analysis of the crude reaction mixture by gas chro-
matography indicated that a 2:1 diastereomeric ratio of products was
generated. Purification by flash chromatography followed by Kugelrohr
distillation afforded 49% of the title compound as a mixture of dia-
stereomers (>96% pure by GC): Rf 0.45 (hexanes); ot 85-95 °C at
1
0.30 mmHg; H NMR (400 MHz, CDCl3) 0.82 (t, J ) 7.4 Hz, 3H),
0.86-0.94 (m, 4H), 1.13-1.38 (m, 4H), 1.42-1.54 (m, 1H), 1.68-
1.77 (m, 1H), 1.87-1.94 (m, 1H), 2.04-2.32 (m, 3H), 2.39-2.48 (m,
1
29
1H), 4.27-4.35 (m, J Si,H ) 192 Hz, 2H), 4.93 (dd, J ) 7.2, 3.2 Hz,
1H), 7.33-7.40 (m, 3H), 7.57-7.59 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ (major diastereomer) 12.00, 15.13, 20.68, 23.96, 28.65, 30.38,
34.79, 35.74, 40.72, 126.25, 127.94, 129.42, 133.08, 135.22, 146.17;
(minor diastereomer) 12.02, 15.28, 20.77, 24.04, 28.76, 30.48, 34.82,
35.74, 40.89, 126.28, 127.94, 129.42, 133.12, 135.22, 146.38; IR (neat)
2134 cm-1; HRMS calcd for C17H26Si 258.1804, found 258.1806;
LRMS (EI) m/z (relative intensity) 258 (20), 201 (39), 123 (59), 107
(100).
(1R*,2R*,3E)-1-[(tert-Butyldimethylsilyl)oxy]-3-(cyclohexylmeth-
ylene)-2-[(phenylsilyl)methyl]cyclopentane (21a). Prepared from 20
according to the general experimental procedure. Purification by flash
chromatography using 6% CH2Cl2 in hexanes followed by Kugelrohr
distillation at reduced pressure afforded 80% of 21a as the major
diastereomer: ot 110-120 °C/0.01 mmHg; Rf 0.33 (10% CH2Cl2 in
(1E)-1-(Cyclohexylmethylene)-2-[(phenylsilyl)methyl]cyclopen-
tane (17a). The reaction of 16 was carried out according to the general
experimental procedure for catalytic cyclization/silylation except 1.5
equiv of PhSiH3 were used. A mixture of 17a and 17b was obtained.
Purification by flash chromatography in hexanes followed by Kugelrohr
distillation afforded 60% of the major product 17a (>99% pure by
1
1
hexanes); H NMR (400 MHz, CDCl3) δ 0.03 (s, 3H), 0.04 (s, 3H),
GC analysis): ot 90-100 °C/0.1 mmHg; Rf 0.45 (hexanes); H NMR
0.87 (s, 9H), 0.91-1.26 (m, 7H), 1.49-1.69 (m, 6H), 1.87-1.96 (m,
1H), 1.99-2.09 (m, 1H), 2.12-2.22 (m, 1H), 2.34-2.46 (m, 2H), 3.73
(400 MHz, CDCl3) δ 0.85-0.92 (m, 1H), 0.96-1.05 (m, 2H), 1.11-
1.37 (m, 5H), 1.42-1.54 (m, 1H), 1.57-1.78 (m, 6H), 1.86-1.94 (m,
1
29
(dt, J ) 6.6, 6.8 Hz, 1H), 4.35 (t, J ) 3.4 Hz, J
) 196 Hz, 2H),
Si,H
(23) (a) Trost, B. M. Science 1991, 254, 1471. (b) Trost, B. M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 259.
(24) (a) Threlkel, R. S.; Bercaw, J. E. J. Organomet. Chem. 1977, 136,
1. (b) Den Haan, K. H.; Teuben, J. H. J. Organomet. Chem. 1987, 322,
321. (c) Den Haan, K. H.; Wielstra, Y.; Eshuis, J. J. W.; Teuben, J. H. J.
Organomet. Chem. 1987, 323, 181.
5.05 (br d, J ) 9.0 Hz, 1H), 7.32-7.37 (m, 3H), 7.56-7.58 (m, 2H);
13C NMR (100 MHz, CDCl3) δ -4.51, -4.18, 12.22, 18.04, 25.26,
25.91, 26.08, 26.18, 32.72, 32.93, 33.03, 37.93, 49.20, 79.25, 127.91,
128.11, 129.37, 133.35, 135.24, 141.23; IR (neat) 2134.5 cm-1; HRMS
calcd for C25H41OSi2 (M - H)+ 413.2696, found 413.2676; LRMS (EI)

Sequential Cyclization/Silylation of Enynes
J. Am. Chem. Soc., Vol. 119, No. 38, 1997 8823
m/z (relative intensity) 414 (0.2), 357 (41), 181 (100), 107 (30). Anal.
Calcd for C25H42OSi2: C, 72.39; H, 10.21. Found: C, 72.28; H, 10.56.
(1R*,2S*,3E)-1-[(tert-Butyldimethylsilyl)oxy]-3-(cyclohexylmeth-
ylene)-2-[(phenylsilyl)methyl]cyclopentane (21b). Prepared from 20
according to the general experimental procedure. Purification by flash
chromatography using 6% CH2Cl2 in hexanes followed by Kugelrohr
distillation at reduced pressure afforded 13% of 21b as the minor
diastereomer: ot 104-110 °C/0.01 mmHg; Rf 0.46 (10% CH2Cl2 in
hexanes); 1H NMR (400 MHz, CDCl3) δ 0.036 (s, 3H), 0.040 (s, 3H),
0.85 (s, 9H), 0.94-1.06 (m, 3H), 1.09-1.30 (m, 4H), 1.53-1.74 (m,
7H), 1.99-2.07 (m, 1H), 2.14-2.23 (m, 1H), 2.31-2.37 (m, 2H), 4.18
81.54, 86.55, 126.83, 127.59, 127.86, 128.40, 129.04, 129.29, 133.03,
135.16, 142.57, 145.31; IR (neat) 2137.0 cm-1; LRMS (EI) m/z (relative
intensity) 243 (100), 165 (28), 105 (16). Anal. Calcd for C38H42OSi:
C, 84.08; H, 7.80. Found: C, 84.49; H, 7.86.
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-1-isoindolino-2-[(phenyl-
silyl)methyl]cyclopentane (27). General NMR-Scale Experimental
Procedure. In the nitrogen atmosphere glovebox 0.018 g (0.068 mmol)
of 26 was weighed in an NMR tube equipped with a J. Young valve.
A solution of 0.002 g (0.004 mmol) of the precatalyst Cp*2YCH3‚THF
in 0.6 mL of benzene-d6 was prepared in a separate vial. This solution
was added to the NMR tube followed by 0.010 g (0.092 mmol) of
phenylsilane. The NMR tube was sealed and removed from the
1
29
(dt, J ) 4.5, 4.6 Hz, 1H), 4.33-4.39 (m, J
) 192 Hz, 2H), 5.01
Si,H
1
(br dd, J ) 9.1, 2.1 Hz, 1H), 7.31-7.39 (m, 3H), 7.55-7.57 (m, 2H);
13C NMR (100 MHz, CDCl3) δ -4.60, -4.29, 8.24, 18.20, 25.06, 25.92,
26.15, 26.23, 32.14, 33.01, 33.10, 38.22, 46.61, 74.97, 127.59, 127.94,
129.38, 133.40, 135.25, 142.45; IR (neat) 2135.2 cm-1; HRMS calcd
for C25H42OSi2 (M - H)+ 413.2696, found 413.2661; LRMS (EI) m/z
(relative intensity) 357 (47), 181 (100), 107 (49), 73 (49). Anal. Calcd
for C25H42OSi2: C, 72.39; H, 10.21. Found: C, 72.64; H, 10.31.
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-2-[(phenylsilyl)methyl]-
1-[(triisopropylsilyl)oxy]cyclopentane (23a) was prepared from 22
according to the general experimental procedure. Analysis of the crude
reaction mixture by gas chromatography indicated that a 12:1 diaster-
eomeric ratio of products was generated. Purification by flash
chromatography followed by Kugelrohr distillation afforded a mixture
of 23a and 23b in 93% yield. Further purification by flash chroma-
tography of a mixture of diastereomers using 10% CH2Cl2 followed
by Kugelrohr distillation afforded a sample of 23a as the major isomer
for characterization (>99% pure by GC analysis): ot 120-150 °C/
glovebox. A H NMR taken after 0.5 h showed the reaction to be
complete. The reaction mixture was diluted with 1 mL of Et2O and
filtered through a column of Florisil. The Florisil was rinsed two times
with 1 mL portions of Et2O. Analysis of the crude reaction mixture
by gas chromatography indicated that a >40:1 diastereomeric ratio of
products was generated. The organics were combined and concentrated
by rotary evaporation followed by removal of solvents at 70 °C/0.01
mmHg to afford 91% (0.025 g, 0.062 mmol) of the desired product as
a mixture of diastereomers: 1H NMR (400 MHz, CDCl3) δ 0.98-
1.34 (m, 7H), 1.61-1.74 (m, 6H), 1.79-1.87 (m, 1H), 2.02-2.10 (m,
1H), 2.21-2.29 (m, 1H), 2.42-2.45 (m, 1H), 2.56-2.61 (m, 1H), 2.86
1
29
(dt, J ) 6.0, 7.8 Hz, 1H), 3.94 (br s, 4H), 4.34 (t, J ) 3.8 Hz, J
Si,H
) 197.5 Hz, 2H), 5.10 (br d, J ) 7.2 Hz, 1H), 7.17 (br s, 4H), 7.24-
7.34 (m, 3H), 7.51-7.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
15.20, 24.06, 26.07, 26.11, 26.17. 26.35, 33.06, 33.09, 38.10, 44.52,
55.11, 69.56, 122.28, 126.48, 127.70, 127.78, 129.03, 134.82, 134.97,
140.05, 143.53; IR (neat) 2134.8 cm-1; HRMS calcd for C27H35NSi
401.2539, found 401.2517; LRMS (EI) m/z (relative intensity) 293 (51),
250 (51), 210 (74), 158 (100), 118 (78). Anal. Calcd for C27H35NSi:
C, 80.74; H, 8.78. Found: C, 80.37; H, 8.93.
1
0.01 mmHg; Rf 0.58 (10% CH2Cl2 in hexanes); H NMR (400 MHz,
CDCl3) δ 0.96-1.05 (m with overlapping broad singlet at 1.02, 23H),
1.10-1.29 (m, 5H), 1.59-1.69 (m, 6H), 1.90-2.07 (m, 2H), 2.16-
2.24 (m, 1H), 2.36-2.45 (m, 2H), 3.91 (dt apparent quartet, J ) 5.1,
(1E,2R*,3S*)-1-(Cyclohexylmethylene)-3-methyl-2-[(phenylsilyl)-
methyl]cyclopentane (28) was prepared from 6 according to the general
experimental procedure. Purification by flash chromatography in
hexanes followed by Kugelrohr distillation afforded 69% of the desired
product (>99% pure by GC analysis): ot 90-115 °C/0.25 mmHg; Rf
0.50 (hexanes); 1H NMR (400 MHz, CDCl3) δ 0.97-1.07 (m, 2H with
overlapping d at 0.98, J ) 6.5 Hz, 3H), 1.11-1.32 (m, 6H), 1.56-
1.71 (m, 6H), 1.83-1.90 (m, 1H), 2.01-2.05 (m, 2H), 2.17-2.23 (m,
1
29
5.1 Hz, 1H), 4.34 (t, J ) 4.0, J
) 194.6 Hz, 2H), 5.07 (dd, J )
Si,H
7.3, 1.9 Hz, 1H), 7.31-7.39 (m, 3H), 7.55-7.57 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 12.43, 13.36, 18.09, 18.12, 25.09, 26.08, 26.19,
32.79, 32.86, 33.06, 38.18, 49.97, 79.56, 127.90, 128.33, 129.39, 133.10,
135.22, 142.02; IR (neat) 2136.4 cm-1; HRMS calcd for C28H48OSi2
456.3244, found 456.3237; LRMS (EI) m/z (relative intensity) 413 (49),
237 (100), 209 (51), 167 (65). Anal. Calcd for C28H48OSi2: C, 73.61;
H, 10.59. Found: C, 74.06; H, 10.69 (sample for elemental analysis
was a mixture diastereomers).
1
29
1H), 2.32-2.38 (m, 1H), 4.29-4.34 (m, J Si,H ) 193.7 Hz, 2H), 5.04
(br d, J ) 8.8 Hz, 1H), 7.32-7.40 (m, 3H), 7.56-7.59 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 13.10, 18.84, 26.11, 26.13, 26.21, 27.76,
32.78, 33.02, 33.11, 38.41, 41.46, 48.20, 127.00, 127.90, 129.32, 133.58,
135.20, 144.90; IR (neat) 2134.6 cm-1; HRMS calcd for C20H30Si
298.2117, found 298.2109; LRMS (EI) m/z (relative intensity) 298 (26),
220 (59), 137 (52), 107 (100).
(1R*,2S*,3E)-3-(Cyclohexylmethylene)-2-[(phenylsilyl)methyl]-1-
[(triisopropylsilyl)oxy]cyclopentane (23b). Purification by flash
chromatography of a mixture of 23a and 23b using 10% CH2Cl2
followed by Kugelrohr distillation afforded a sample of the minor
product 23b for characterization (>98% pure by GC analysis): ot 120-
150 °C/0.01 mmHg; Rf 0.62 (10% CH2Cl2 in hexanes); 1H NMR (400
MHz, CDCl3) δ 0.85-0.94 (m, 1H), 0.98-1.07 (m with overlapping
broad singlet at 1.03, 23H), 1.12-1.27 (m, 2H), 1.32-1.39 (m, 1H),
1.58-1.68 (m, 6H), 1.71-1.82 (m, 2H), 1.99-2.04 (m, 1H), 2.11-
2.19 (m, 1H), 2.32-2.39 (m, 1H), 2.40-2.44 (m, 1H), 4.24 (dt, J )
(1E,2S*,3R*)-1-(Cyclohexylmethylene)-3-ethyl-2-[(phenylsilyl)-
methyl]cyclopentane (29) was prepared from 7 according to the general
experimental procedure. Purification by flash chromatography using
hexanes followed by Kugelrohr distillation to afford 88% of the desired
product (>97% pure by GC analysis): ot 80-100 °C/0.02 mmHg; Rf
1
1
29
5.8, 6.4 Hz, 1H), 4.32-4.36 (m, J
) 196 Hz, 2H), 5.05 (br d, J
0.47 (hexanes); H NMR (400 MHz, CDCl3) δ 0.86 (t, J ) 7.3 Hz,
Si,H
) 7.7 Hz, 1H), 7.30-7.38 (m, 3H), 7.54-7.56 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 7.93, 12.45, 18.11, 18.14, 24.41, 26.06, 26.17,
31.63, 32.96, 37.96, 46.79, 75.11, 127.88, 128.50, 129.30, 133.29,
135.25, 141.49; IR (neat) 2137.5 cm-1; HRMS calcd for C28H48OSi2
456.3244, found 456.3217; LRMS (EI) m/z (relative intensity) 413 (29),
237 (100), 209 (52), 167 (65).
3H), 0.97-1.31 (m, 9H), 1.42-1.71 (m, 7H), 1.87-1.95 (m, 1H), 2.00-
2.09 (m, 1H), 2.12-2.21 (m, 2H), 2.23-2.37 (m, 1H), 4.27-4.34 (m,
1
29
J
Si,H ) 195 Hz, 2H), 5.03 (dd, J ) 9.0, 2.4 Hz, 1H), 7.32-7.40 (m,
3H), 7.55-7.58 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 12.29, 13.87,
26.12, 26.20, 26.77, 27.56, 29.77, 33.04, 33.13, 38.45, 46.28, 48.43,
126.96, 127.89, 129.31, 133.58, 135.19, 145.01; IR (neat) 2134.3 cm-1
;
HRMS calcd for C21H32Si 312.2273, found 312.2255; LRMS (EI) m/z
(relative intensity) 312 (19), 283 (12), 234 (30), 107 (100).
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-2-[(phenylsilyl)methyl]-
1-[(triphenylmethyl)oxy]cyclopentane (25). Prepared from 24 ac-
cording to the general experimental procedure. Analysis of the crude
reaction mixture by gas chromatography indicated that a 24:1 diaster-
eomeric ratio of products was generated. Purification by flash
chromatography using 5% Et2O in hexanes followed by removal of
solvents at 50 °C/0.01 mmHg afforded 88% of the desired product as
(1E,2R*,3S*)-1-(Cyclohexylmethylene)-3-[(methoxy)methyl]-2-
[(phenylsilyl)methyl]cyclopentane (30). The reaction of 8 was carried
out according to the general experimental procedure except the reaction
was run in a sealed tube at 100 °C. Analysis of the crude reaction
mixture by gas chromatography indicated that a 20:1 diastereomeric
ratio of products was generated. Purification by flash chromatography
using 10% Et2O in hexanes followed by Kugelrohr distillation afforded
80% of the desired product as a mixture of diastereomers (>99% pure
by GC analysis): ot 90-100 °C/0.01 mmHg; Rf 0.17 (3% Et2O in
hexanes); 1H NMR (400 MHz, CDCl3) δ 1.00 (br q, J ) 12.0 Hz, 2H),
1.12-1.30 (m, 5H), 1.34-1.44 (m, 1H), 1.57-1.71 (m, 5H), 1.86-
1
a mixture of diastereomers: Rf 0.60 (5% Et2O in hexanes); H NMR
(400 MHz, CDCl3) δ 0.85 (dt, J ) 7.5, 3.7 Hz, 2H), 1.00-1.37 (m,
6H), 1.45-1.77 (m, 6H), 2.07-2.15 (m, 2H), 2.38-2.50 (m, 2H), 3.68
1
29
(dt, J ) 4.6, 2.3 Hz, 1H), 4.16 (t, J ) 3.9, J
) 194.9 Hz, 2H),
Si,H
5.09 (br d, J ) 9.2 Hz, 1H), 7.21-7.56 (m, 20H); 13C NMR (100 MHz,
CDCl3) δ 14.53, 25.45, 26.08, 26.19, 30.39, 32.98, 33.09, 38.52, 48.50,

8824 J. Am. Chem. Soc., Vol. 119, No. 38, 1997
Molander and Retsch
1.97 (m, 2H), 1.98-2.07 (m, 1H), 2.18-2.25 (m, 1H), 2.29-2.36 (m,
2H), 3.20 (dd, J ) 9.1, 7.0 Hz, 1H), 3.29 (s, 3H), 3.32 (dd, J ) 9.1,
(2.45 mmol) of 90% t-BuOOH solution was weighed out and 1.2 mL
of DMF was added. To this solution at 0 °C, 0.103 g (2.56 mmol) of
KH was slowly added. This produced a slightly foamy pink solution
which was allowed to warm to room temperature. A solution of 21a,
105 mg, 0.25 mmol, 0.2 M in DMF was slowly added via syringe.
After 3 h of stirring at room temperature, no starting material could be
detected by TLC. To this solution 0.5 g of Na2S2O3‚5H2O was slowly
added and the sides of the flask were rinsed down with hexanes. All
of the volatiles were removed in vacuo. The resulting solids were
extracted with CHCl3, concentrated, and flashed using 1:1 EtOAc/
hexanes followed by EtOAc. Concentration followed by recrystalli-
zation from CHCl3 afforded 80% (0.042 mg, 0.20 mmol) of the diol
36 as white needle-like crystals (>99% pure by GC analysis): mp 107
°C; Rf 0.50 (in EtOAc); 1H NMR (400 MHz, CDCl3) δ 0.93-1.28 (m,
5H), 1.52-1.68 (m, 6H), 1.95-2.06 (m, 2H), 2.12-2.22 (m, 2H), 2.37-
2.44 (m, 2H), 2.60 (br s, 1H), 3.58 (dd, J ) 10.7, 8.2 Hz, 1H), 3.80
(dd, J ) 10.7, 4.9 Hz, 1H), 4.04 (dt, J ) 6.8, 7.0 Hz, 1H), 4.98 (dq,
J ) 9.1, 2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 25.67, 25.95,
26.01, 32.40, 32.76, 33.07, 38.06, 53.35, 64.51, 129.32, 136.99; IR
(neat) 3388 cm-1 (br); HRMS calcd for C13H22O2 210.1620, found
210.1606; LRMS (EI) m/z (relative intensity) 210 (13), 192 (48), 161
(80), 81 (100). Anal. Calcd for C13H22O2: C, 74.24; H, 10.54.
Found: C, 74.09; H, 10.68.
1
29
5.9 Hz, 1H), 4.28-4.33 (m, J Si,H ) 195 Hz, 2H), 5.05 (dd, J ) 9.1,
2.1 Hz, 1H), 7.31-7.39 (m, 3H), 7.55-7.58 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 14.94, 26.08, 26.17, 27.14, 27.60, 33.02, 33.09, 38.54,
43.48, 46.53, 58.77, 75.94, 127.60, 127.91, 129.36, 133.28, 135.22,
144.34; IR (neat) 2134.5 cm-1; HRMS calcd for C21H32OSi 328.2222,
found 328.2218; LRMS (EI) m/z (relative intensity) 137 (31), 107 (100),
91 (37).
(1E,2R*,3S*)-3-[[(tert-Butyldimethylsilyl)oxy]methyl]-1-(cyclo-
hexylmethylene)-2-[(phenylsilyl)methyl]cyclopentane (31) was pre-
pared from 10 according to the general experimental procedure.
Purification by flash chromatography using hexanes followed by
Kugelrohr distillation afforded 76% of 31: ot 90-110 °C/0.03 mmHg;
Rf 0.32 (10% CH2Cl2 in hexanes); 1H NMR (400 MHz, CDCl3) δ 0.00
(s, 6H), 0.86 (s, 9H), 0.95-1.04 (m, 2H), 1.09-1.28 (m, 5H), 1.34-
1.44 (m, 1H), 1.57-1.71 (m, 5H), 1.78-1.88 (m, 2H), 1.97-2.06 (m,
1H), 2.15-2.32 (m, 2H), 2.35-2.40 (m, 1H), 3.42 (B of ABX, J )
5.9, 6.2 Hz, 1H), 3.52 (A of ABX, J ) 5.9, 5.2 Hz, 1H), 4.26-4.33
1
29
(m, J
) 193.2 Hz, 2H), 5.03 (dd, J ) 9.2, 2.0 Hz, 1H), 7.30-
Si,H
7.38 (m, 3H), 7.54-7.56 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
-5.35, 15.00, 18.37, 25.99, 26.11, 26.20, 26.95, 27.03, 33.06, 33.13,
38.55, 42.93, 48.97, 65.60, 127.53, 127.91, 129.34, 133.35, 135.25,
144.75; IR (neat) 2134.2 cm-1; HRMS calcd for C26H43OSi2: (M -
H)+ 427.2853, found 427.2823; LRMS (EI) m/z (relative intensity) 296
(22), 213 (72), 181 (44), 135 (44), 107 (53), 41 (100). Anal. Calcd
for C26H44OSi2: C, 72.83; H, 10.34. Found: C, 73.00; H, 10.41.
(1R*,2R*,2′R*/S*,3E)-3-[2′-[(tert-Butyldimethylsilyl)oxy]propyl-
ene]-2-[(phenylsilyl)methyl]-1-[(triisopropylsilyl)oxy]cyclopentane
(33) was prepared from 32 according to the general experimental
procedure. Purification by flash chromatography using 10% CH2Cl2
in hexanes followed by solvent removal at 0.04 mmHg afforded 83%
(0.057 g, 0.092 mmol) of the title compound as a 1.6:1 mixture of
diastereomers: Rf 0.30 (10% CH2Cl2 in hexanes); 1H NMR (400 MHz,
CDCl3) δ 0.06 (d, J ) 4.3 Hz, 3.6H), 0.08 (d, J ) 4.8 Hz, 2.4H),
0.69-0.89 (m with 2 overlapping singlets at 0.85 and 0.89, 11H), 1.01-
1.23 (m with 2 overlapping doublets at 1.10, J ) 6.4 Hz and 1.23, J )
6.3 Hz, 4H), 1.34-1.55 (m, 1H), 1.99-2.16 (m, 1H), 2.24-2.47 (m,
2H), 3.63-3.65 (m, 0.6H), 3.69-3.72 (m, 0.4H), 4.05-4.10 (m, 0.8H),
4.11-4.19 (m, 1.2H), 4.34-4.43 (m, 1H), 5.24 (br d, J ) 8.4 Hz, 0.4H)
and 5.29 (br d, J ) 8.3 Hz, 0.6H), 7.18-7.31 (m, 12H), 7.34-7.54
(m, 8H); 13C NMR (100 MHz, CDCl3) (major diasteromer) δ -4.73,
-4.43, 14.62, 18.27, 24.37, 25.63, 25.91, 30.12, 48.59, 67.39, 81.12,
86.66, 126.88, 127.57, 127.63, 127.92, 128.98, 129.37, 132.76, 135.14,
143.84, 145.20; (minor diastereomer) -4.73, -4.24, 14.92, 18.29,
24.40, 25.32, 25.99, 30.44, 48.90, 67.42, 81.17, 86.83, 126.86, 127.63,
127.72, 127.91, 128.78, 128.98, 132.69, 135.10, 143.55, 145.18; IR
(neat) 2138.0 cm-1; LRMS (EI) m/z (relative intensity) 375 (11), 243
(100), 165 (64), 105 (10), 73 (28). Anal. Calcd for C40H50O2Si2: C,
77.69; H, 8.14. Found: C, 77.49; H, 7.95.
(1E)-6-[(tert-Butyldimethylsilyl)oxy]-1-cyclohexyl-2-(phenylsilyl)-
1,7-octadiene (38). The reaction of 37 was carried out according to
the general experimental procedure except the reaction was stirred for
21 h. Purification by flash chromatography using 3% Et2O in hexanes
followed by Kugelrohr distillation afforded 93% of the title com-
pound: ot 95-110 °C/0.01 mmHg; Rf 0.57 (3% Et2O in hexanes); 1H
NMR (400 MHz, CDCl3) δ 0.02 (s, 3H), 0.03 (s, 3H), 0.89 (s, 9H),
1.05-1.50 (m, 9H), 1.60-1.73 (m, 5H), 2.18 (br t, J ) 6.5 Hz, 2H),
1
29
2.36-2.44 (m, 1H), 4.01 (br dt, J ) 5.9, 5.9 Hz, 1H), 4.52 (s, J
Si,H
) 195 Hz, 2H), 4.99 (dd, J ) 10.4, 1.2 Hz, 1H), 5.10 (dd, J ) 17.2,
1.4 Hz, 1H), 5.85 (ddd, J ) 17.0, 10.4, 6.0 Hz, 1H), 5.85 (br d, J )
9.2 Hz, 1H), 7.32-7.40 (m, 3H), 7.55-7.57 (m, 2H); 13C NMR (100
MHz, CDCl3) δ -4.83, -4.39, 18.22, 25.64, 25.76, 25.83, 25.88, 25.92,
26.00, 30.48, 32.83, 37.70, 38.02, 73.72, 113.44, 127.96, 129.44, 131.47,
132.69, 135.50, 141.69, 152.17; IR (neat) 2131.7 cm-1; HRMS calcd
for C26H43OSi2 (M - H+) 427.2853, found 427.2831; LRMS (EI) m/z
(relative intensity) 265 (32), 181 (71), 105 (20), 75 (100). Anal. Calcd
for C26H44OSi2: C, 72.83; H, 10.34. Found: C, 72.85; H, 10.59.
(1R*,2R*,3E)-1-[(tert-Butyldimethylsilyl)oxy]-3-(cyclohexylmeth-
ylene)-2-[(hexylsilyl)methyl]cyclohexane (39). The reaction of 37 was
carried out according to the general experimental procedure except
hexylsilane was used in the place of phenylsilane and the reaction was
run for 22 h. Purification by flash chromatography in hexanes afforded
1
47% of the title compound: Rf 0.50 (hexanes); H NMR (400 MHz,
CDCl3) δ -0.02 (s, 3H), 0.00 (s, 3H), 0.59-0.65 (m, 2H), 0.69-0.77
(m, 1H), 0.79-0.88 (m, 2H, with overlapping singlet at 0.79, 9H),
0.91-1.45 (m, 16H), 1.53-1.72 (m, 7H), 1.77-1.84 (m, 1H), 1.98-
2.06 (m, 3H), 2.13-2.21 (m, 1H), 3.42-3.45 (m, 1H), 3.54-3.62 (m,
(1R*,2R*,3E)-3-[5′-(2′,2′-Dimethyl-1′,3′-dioxanyl)methylene]-2-
[(phenylsilyl)methyl]-1-[(triphenylmethyl)oxy]cyclopentane (35) was
prepared from 34 according to the general experimental procedure.
Analysis of the crude reaction mixture by gas chromatography indicated
that a 35:1 diastereomeric ratio of products was formed. Purification
by flash chromatography using 10% Et2O in hexanes followed by
removal of solvents at 70 °C/0.01 mmHg to afford 88% of the desired
product as a mixture of diastereomers (>99% pure by GC analysis):
Rf 0.41 (20% Et2O in hexanes); 1H NMR (400 MHz, CDCl3) δ 0.74-
0.79 (m, 2H), 1.20-1.28 (m, 1H), 1.34-1.51 (m, 1H, with 2
overlapping singlets, 1.39, 3H and 1.44, 3H), 2.07-2.15 (m, 1H), 2.34-
2.48 (m, 2H), 2.62-2.73 (m, 1H), 3.48-3.68 (m, 4H), 3.76-3.81 (m,
1
29
J
Si,H ) 182.5 Hz, 2H), 4.9 (d, J ) 8.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ -4.68, -4.51, 9.56, 10.01, 14.11, 18.05, 22.56, 23.19, 25.46,
25.82, 26.11, 26.17, 31.51, 31.55, 32.57, 33.76, 33.86, 36.44, 49.84,
75.48, 130.25, 136.46; IR (neat) 2124.5 cm-1; LRMS (EI) m/z (relative
intensity) 379 (35), 189 (78), 171 (95), 105 (100), 73 (82). Anal. Calcd
for C26H52OSi2: C, 71.48; H, 12.00. Found: C, 71.76; H, 11.77.
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-2-(hydroxymethyl)-1-cy-
clohexanol (41). The oxidation of 39 was carried out according to
the general procedure outlined for the oxidation of 21a with the
exception that the reaction was heated to 70 °C for 24 h. Purification
by flash chromatography in 1:1 ethyl acetate/hexanes followed by
recrystallization from hexanes afforded 13% of the expected diol as
white needle-like crystals (>98% pure by GC analysis): mp 68 °C; Rf
1
29
1H), 4.06 (t, J ) 3.4 Hz, J
) 192 Hz, 2H), 4.78 (br d, J ) 9.0
Si,H
Hz, 1H), 7.18-7.49 (m, 20H); 13C NMR (100 MHz, CDCl3) δ 14.26,
19.18, 25.91, 28.95, 30.36, 36.19, 49.03, 63.94, 63.99, 81.37, 86.75,
97.37, 117.35, 127.00, 127.72, 128.01, 129.02, 129.53, 132.62, 135.15,
145.16, 149.77; IR (neat) 2136.1 cm-1; HRMS calcd for C37H39O3Si:
(M - CH3)+ 559.2668, found 559.2680; LRMS (EI) m/z (relative
intensity) 243 (100), 165 (86), 105 (73).
1
0.26 (1:1 EtOAc/hexanes); H NMR (400 MHz, CDCl3) δ 0.96-1.37
(m, 6H), 1.50-1.76 (m, 7H), 1.84-1.90 (m, 2H), 2.14-2.24 (m, 2H),
2.30-2.38 (m, 2H), 2.62 (br d, J ) 4.8, 1H), 3.62-3.68 (m, 1H), 3.77-
3.91 (m, 2H), 4.86 (d, J ) 8.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 23.78, 25.95, 27.65, 33.63, 33.78, 33.83, 36.56, 52.55, 64.15, 74.64,
130.70, 134.37; IR (neat) 3349 cm-1 (br); LRMS (EI) m/z (relative
intensity) 206 (93), 163 (65), 135 (66), 81 (100). Anal. Calcd for
C14H24O2: C, 74.95; H, 10.78. Found: C, 75.29; H, 10.89. The relative
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-2-(hydroxymethyl)-1-cy-
clopentanol (36). General Procedure for the Oxidation/Deprotec-
tion of 21a. In a 50 mL Schlenk flask purged with argon 0.245 g

Sequential Cyclization/Silylation of Enynes
J. Am. Chem. Soc., Vol. 119, No. 38, 1997 8825
stereochemistry was determined by single-crystal X-ray crystal dif-
fractometry.
137.98; IR (neat) 3356 cm-1 (br); LRMS (EI) m/z (relative intensity)
208 (21), 190 (60), 108 (100), 95 (97). Anal. Calcd for C14H24O: C,
80.71; H, 11.61. Found: C, 80.76; H, 11.61. Alcohol 43 was isolated
as the minor product of the reaction (>99% pure by GC analysis): Rf
(1R*,2R*,3E)-3-(Cyclohexylmethylene)-2-methyl-1-cyclohexa-
nol (42) and (1R*,2S*,3E)-3-(Cyclohexylmethylene)-2-methyl-1-cy-
clohexanol (43). The reaction of 37 with PhMeSiH2 was run in an
NMR tube according to the general procedure outlined for the
preparation of 27. The reaction was run at 50 °C for 8 h. Standard
workup procedures were employed to isolate a crude mixture of 40 as
inseparable isomers. To simplify characterization the crude reaction
mixture was treated with 2 equiv of 0.5 M TBAF in THF. After 20 h
of stirring at room temperature, the reaction was diluted with Et2O and
washed with H2O and brine, and the aqueous layers were extracted
with Et2O. The combined organic extracts were dried over MgSO4
and concentrated in vacuo. Analysis of the crude reaction mixture by
1H NMR indicated that a 4:1 diastereomeric ratio of products was
generated. Purification by column chromatography using 20% EtOAc
in hexanes afforded a mixture of 42 and 43 in 84% yield. The two
diastereomers were isolated independently for characterization. De-
termination of the relative stereochemistry was based on 1H NMR
decoupling experiments. Alcohol 42 was isolated as the major product
of the reaction (>99% pure by GC analysis): mp 74 °C; Rf 0.30 (20%
1
0.36 (20% EtOAc in hexanes); H NMR (500 MHz, CDCl3) δ 1.00-
1.31 (m, 6H, with overlapping doublet at 1.01, J ) 6.0, 3H), 1.47-
1.63 (m, 6H), 1.66-1.70 (m, 2H), 1.73-1.84 (m, 2H), 2.18-2.24 (m,
1H), 2.33 (ddq, J ) 7.0, 3.1, 1.3 Hz, 1H), 2.37-2.41 (m, 1H), 3.73-
3.77 (m, 1H), 4.97 (d, J ) 8.7 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ 13.85, 23.22, 26.06, 26.10, 27.75, 32.37, 33.72, 34.19, 36.43, 43.87,
72.82, 130.22, 137.46; IR (neat) 3382 cm-1 (br); HRMS calcd for
C14H24O: 208.1827, found 208.1827; LRMS (EI) m/z (relative intensity)
208 (16), 190 (31), 135 (33), 111 (85), 108 (75).
Acknowledgment. We gratefully acknowledge the National
Institutes of Health (GM48580) for their generous support of
this research. In addition, we would also like to thank Dr. Bruce
C. Noll for performing the X-ray crystal structure determina-
tions.
Supporting Information Available: Experimental details
and characterization for intermediates 1-10, 12-16, 18, 20,
22, 24, 26, 32, 34, and 37 and crystallographic data and tables
for 36 and 41 (38 pages). See any current masthead page for
ordering information and Internet access instructions.
1
CH2Cl2/20% Et2O in hexanes); H NMR (400 MHz, CDCl3) δ 0.96-
1.37 (m, 6H, with overlapping doublet at 1.08, J ) 6.9, 3H), 1.42-
1.73 (m, 8H), 1.81-1.94 (m, 2H), 2.00 (br dq, J ) 7.5, 6.6 Hz, 1H),
2.12-2.22 (m, 1H), 2.31-2.37 (m, 1H), 3.24-3.30 (m, 1H), 4.98 (d,
J ) 8.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.97, 24.13, 26.05,
26.07, 26.08, 27.17, 32.94, 33.87, 33.88, 36.47, 46.42, 75.48, 129.42,
JA971538G