Selectivity control in alkylidene carbene-mediated C-H insertion and allene formation

Article abstract of DOI:10.1021/jo102180f

Regioselectivity of alkylidene carbene-mediated C-H insertion was explored utilizing electronic, conformational, steric, and stereoelectronic effects. Relying on these factors, highly regio-and chemoselective carbene insertion reaction of C-H bonds in different environments could be obtained. The observed selectivity clearly indicates that an electronic effect plays a more important role than steric effect. In general, C-H bonds in conformationally rigid cyclic environments are less reactive than those in acyclic systems toward carbene insertion, and in this situation, a competing intermolecular reaction between alkylidene carbene and trimethylsilyldiazomethane led to the formation of allenylsilanes. The formation of allenylsilane becomes more favorable as the concentration of reaction becomes higher, as well as the C-H bonds undergoing insertion becomes electronically and conformationally deactivated.

Full text of DOI:10.1021/jo102180f

pubs.acs.org/joc
Selectivity Control in Alkylidene Carbene-Mediated C-H Insertion
and Allene Formation
Jun-Cheng Zheng,† Sang Young Yun, Chunrui Sun, Nam-Kyu Lee, and Daesung Lee*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607,
United States. †Present address: Boehringer Ingelheim International Trading (Shanghai) Co., Ltd. 5F,
Building 78, No. 90 Delin Road, Waigaoqiao Free Trade Zone, Shanghai 200131, People’s Republic of China
dsunglee@uic.edu
Received November 4, 2010
Regioselectivity of alkylidene carbene-mediated C-H insertion was explored utilizing electronic,
conformational, steric, and stereoelectronic effects. Relying on these factors, highly regio- and
chemoselective carbene insertion reaction of C-H bonds in different environments could be
obtained. The observed selectivity clearly indicates that an electronic effect plays a more important
role than steric effect. In general, C-H bonds in conformationally rigid cyclic environments are less
reactive than those in acyclic systems toward carbene insertion, and in this situation, a competing
intermolecular reaction between alkylidene carbene and trimethylsilyldiazomethane led to the
formation of allenylsilanes. The formation of allenylsilane becomes more favorable as the concen-
tration of reaction becomes higher, as well as the C-H bonds undergoing insertion becomes
electronically and conformationally deactivated.
Introduction
able behavior, a variety of chemoselective transformations
including C-H insertion,1 Fritsch-Buttenberg-Wiechell
rearrangement,2 nucleophilic substitution,3 and [1 þ 2]
cycloaddition4,5 reactions have been developed as powerful
synthetic tools.1 Among these reaction categories, C-H
insertion has gained most significant attention due to its
unique feature to generate five-membered carbocyclic or
heterocyclic6 systems with a stereochemically defined qua-
ternary carbon center. Thus, many approaches to generate
alkylidene carbene species have been developed and utilized
to construct a diverse array of molecular architecture.7,8
Wolinsky and Gilbert have extensively investigated the
reactivity of alkylidene carbenes toward various types of
C-H bonds for insertion including primary, secondary,
Alkylidene carbenes and carbenoids are versatile intermedi-
ates widely used in organic synthesis.1 On the basis of their high
reactivity due to a strong electrophilic nature yet controll-
(1) For reviews, see: (a) Stang, P. J. Chem. Rev. 1978, 78, 383. (b) Taber,
D. F. In Methods of Organic Chemistry, 4th ed.; Helmchen, G., Ed.; Georg
Thieme Verlag: New York, 1995; Vol. E21, p 1127. (c) Kirmse, W. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1164. (d) Knorr, R. Chem. Rev. 2004, 104,
3795.
(2) (a) Fritsch, P. Liebigs Ann. Chem. 1894, 272, 319. (b) Buttenberg,
W. P. Liebigs Ann. Chem. 1894, 272, 324. (c) Wiechell, H. Liebigs Ann. Chem.
1894, 272, 337.
(3) Maercker, A. In Lithium Chemistry; Sapse, A.-M., Schleyer, P. v. R.,
Eds.; Wiley: New York, 1995; pp 477-577, see p 491.
(4) (a) Gilbert, J. C.; Giamalva, D. H. J. Org. Chem. 1992, 57, 4185.
(b) Ochiai, M.; Sueda, T.; Uemura, K.; Masaki, Y. J. Org. Chem. 1995, 60,
2624. (c) Cunico, R. F.; Han, Y.-K. J. Organomet. Chem. 1978, 162, 1. (d)
Patrick, T. B.; Haynie, E. C.; Probst, W. J. J. Org. Chem. 1972, 37, 1553. (e)
Stang, P. J.; Mangum, M. G. J. Am. Chem. Soc. 1975, 97, 6478. (f) Fox, D. P.;
Bjork, J. A.; Stang, P. J. J. Org. Chem. 1983, 48, 3994. (g) Sakai, A.; Aoyama,
T.; Shioiri, T. Tetrahedron 1999, 55, 3687.
(6) For selected examples of the formation of 2,5-dihydrofurans, see:
(a) Buxton, S. R.; Holm, K. H.; Skattebøl, L. Tetrahedron Lett. 1987, 28,
2167. (b) Baird, M. S.; Baxter, A. G. W.; Hoorfar, A.; Jefferies, I. J. Chem.
Soc., Perkin Trans. 1 1991, 2575. (c) Ohira, S.; Kitamura, T.; Tsuda,
K.; Fujiwara, Y. Tetrahedron Lett. 1998, 39, 5375–5376. (d) Singh, G.;
Vankayalapati, H. Tetrahedron: Asymmetry 2000, 11, 125. For the study
on selectivity in dihydrofuran formation, see: (e) Taber, D. F.; Christos, T. E.
Tetrahedron Lett. 1997, 38, 4927.
€
(5) (a) Kobrich, G.; Heinemann, H. Chem. Commun. 1969, 493.
(b) Kobrich, G. Angew. Chem., Int. Ed. Engl. 1967, 6, 41. (c) Rule, M.;
€
Salinaro, R. F.; Pratt, D. R.; Berson, J. A. J. Am. Chem. Soc. 1982, 104, 2223.
(d) Salinaro, R. F.; Berson, J. A. J. Am. Chem. Soc. 1979, 101, 7094.
1086 J. Org. Chem. 2011, 76, 1086–1099
Published on Web 01/18/2011
DOI: 10.1021/jo102180f
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2011 American Chemical Society

Zheng et al.
JOCArticle
SCHEME 1
tertiary, and benzylic C-H bonds, and found a preference
for insertion into the C-H bonds of higher degree.9,10
However, the reactivity and selectivity between the same
degrees of C-H bonds on structurally or conformationally
biased systems are yet to be defined. For example, the extent
of selectivity of insertion into C-H bonds on cyclic and acyclic
systems or C-H bonds on six- and five-membered-ring
systems is not easily predictable due to lack of systematic
investigation. While the C-H bonds attached to a carbon
carrying one or more heteroatoms are generally known to be
more reactive toward carbene insertion,11 the exact role of
these heteroatoms in C-H insertion is not well character-
ized. Recently, an investigation of C-H insertion of var-
iously substituted and conformationally constrained systems
revealed high selectivity between two competing C-H
bonds, which is believed to be the manifestation of a strong
stereoelectronic effect of oxygen substituents. In the context
of platensimycin12 synthesis,13 this regioselective C-H in-
sertion based on the stereoelectronic effect of oxygen has
led to a rapid construction of the key quaternary carbon-
containing platensimycin core 313a (Scheme 1).
While optimizing the C-H insertion, we also observed
allenylsilane as a byproduct, which sometimes became a
predominant product. Subsequently, the formation of sily-
lallenes was found to be a general phenomenon rather than
an exception in conformationally constrained systems. Since
allenes play critical roles in metal-catalyzed reactions and
constitute a structural subunit in many natural products,14,15
diverse synthetic approaches have been developed for their
preparation.16 However, the synthesis of functionalized
allenes with various heteroatom substituents such as the silyl
group are still in demand. The novel reaction mechanism of
this allenylsilane formation and their potential utility
prompted us to explore the scope and generality of this
new allene-forming reaction.
In this article, we delineate two major selectivity issues in
the alkylidene carbene-mediated transformations employing
(13) (a) Yun, S. Y.; Zheng, J.-C.; Lee, D. J. Am. Chem. Soc. 2009, 131,
8413. (b) Nicolaou, K. C.; Li, A.; Edmonds, D. J. Angew. Chem., Int. Ed.
2006, 45, 7086. (c) Nicolaou, K. C.; Edmonds, D. J.; Li, A.; Tria, G. S. Angew.
Chem., Int. Ed. 2007, 46, 3942. (d) Zou, Y.; Chen, C.-H.; Taylor, C. D.;
Foxman, B. M.; Snider, B. B. Org. Lett. 2007, 9, 1825. (e) Nicolaou, K. C.;
Tang, Y.; Wang, J. Chem. Commun. 2007, 1922. (f) Tiefenbacher, K.; Mulzer,
J. Angew. Chem., Int. Ed. 2007, 46, 8074. (g) Li, P.; Payette, J. N.; Yamamoto,
H. J. Am. Chem. Soc. 2007, 129, 9534. (h) Lalic, G.; Corey, E. J. Org. Lett.
2007, 9, 4921. (i) Nicolaou, K. C.; Pappo, D.; Tsang, K. Y.; Gibe, R.; Chen,
D. Y.-K. Angew. Chem., Int. Ed. 2008, 47, 944. (j) Kim, C. H.; Jang, K. P.;
Choi, S. Y.; Chung, Y. K.; Lee, E. Angew. Chem., Int. Ed. 2008, 47, 4009.
(k) Matsuo, J.-I.; Takeuchi, K.; Ishibashi, H. Org. Lett. 2008, 10, 4049.
(l) Ghosh, A. K.; Xi, K. J. Org. Chem. 2009, 74, 1163. For reviews, see:
(m) Tiefenbacher, K.; Mulzer, J. Angew. Chem., Int. Ed. 2008, 47, 2548.
(n) Nicolaou, K. C.; Chen, J. S.; Edmonds, D. J.; Estrada, A. A. Angew.
Chem., Int. Ed. 2009, 48, 660. (o) Palanichamy, K.; Kaliappan, K. P. Chem.
Asian J. 2010, 5, 668. (p) McGrath, N. A.; Bartlett, E. S.; Sittihan, S.;
Njardarson, J. T. Angew. Chem., Int. Ed. 2009, 48, 8543. (q) Beaulieu, M.-A.;
(7) (a) Gilbert, J. C.; Blackburn, B. K. J. Org. Chem. 1986, 51, 3656.
(b) Taber, D. F.; Walter, R.; Meagley, R. P. J. Org. Chem. 1994, 59, 6014.
(c) Taber, D. F.; Meagley, R. P.; Doren, D. J. J. Org. Chem. 1996, 61, 5723.
(d) Taber, D. F.; Neubert, T. D.; Rheingold, A. L. J. Am. Chem. Soc. 2002,
124, 12416. (e) Wardrop, D. J.; Zhang, W.; Fritz, J. Org. Lett. 2002, 4, 489.
(f) Taber, D. F.; Storck, P. H. J. Org. Chem. 2003, 68, 7768. (g) Taber, D. F.;
Sikkander, M. I.; Storck, P. H. J. Org. Chem. 2007, 72, 4098. (h) Erickson,
K. L.; Wolinsky, J. J. Am. Chem. Soc. 1965, 87, 1142. (i) Walsh, R. A.;
Bottini, A. T. J. Org. Chem. 1970, 35, 1086. (j) Gilbert, J. C.; Weerasooriya,
U.; Giamalva, D. Tetrahedron Lett. 1979, 35, 4619. (k) Hauske, J. R.;
Guadliana, M.; Desai, K. J. Org. Chem. 1982, 47, 5019. (l) Fisher, R. H.;
€
ꢀ
Baumann, M.; Kobrich, G. Tetrahedron Lett. 1974, 15, 1207. (m) Hayes,
Sabot, C.; Achache, N.; Guerard K. G.; Canesi, S. Chem.;Eur. J. 2010, 16,
C. J.; Sherlock, A. E.; Green, M. P.; Wilson, C.; Blake, A. J.; Selby, M. D.;
Prodger, J. C. J. Org. Chem. 2008, 73, 2041.
11224. (r) Nicolaou, K. C.; Lister, T.; Denton, R. M.; Montero, A.;
Edmonds, D. J. Angew. Chem., Int. Ed. 2007, 46, 4712. (s) Nicolaou,
K. C.; Tang, Y.; Wang, J.; Stepan, A. F.; Li, A.; Montero, A. J. Am. Chem.
Soc. 2007, 129, 14850. (t) Nicolaou, K. C.; Stepan, A. F.; Lister, T.; Li, A.;
Montero, A.; Tria, G. S.; Turner, G. I.; Tang, Y.; Wang, J.; Denton, R. M.;
Edmonds, D. J. J. Am. Chem. Soc. 2008, 130, 13110. (u) Yeung, Y.-Y.; Corey,
E. J. Org. Lett. 2008, 10, 3877. (v) Jang, K. P.; Kim, C. H.; Na, S. W.; Jang,
D. S.; Kim, H.; Kang, H.; Lee, E. Bioorg. Med. Chem. Lett. Submitted for
publication. For biosynthesis, see: (w) Herath, K. B.; Attygalle, A. B.; Singh,
S. B. J. Am. Chem. Soc. 2007, 129, 15422. (x) Herath, K.; Attygalle, A. B.;
Singh, S. B. Tetrahedron Lett. 2008, 49, 5755.
(14) For reviews, see: (a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.;
Khan, F. A. Chem. Rev. 2000, 100, 3067. (b) Marshall, J. A. Chem. Rev. 2000,
100, 3163. (c) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590. (d) Lu.,
X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (e) Bates, R. W.;
Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12. (f) Sydnes, L. K. Chem. Rev.
2003, 103, 1133. (g) Tius, M. A. Acc. Chem. Res. 2003, 36, 284. (h) Ma, S. Acc.
Chem. Res. 2003, 36, 701. (i) Wei, L.-L.; Xiong, H.; Hsung, R. P. Acc. Chem.
Res. 2003, 36, 773. (j) Ma, S. Chem. Rev. 2005, 105, 2829. (k) Brummond,
K. M.; DeForrest, J. E. Synthesis 2007, 795. (l) Krause, N., Ed. Science of
Synthesis; Georg Thieme Verlag: Stuttgart, Germany, 2007; Vol. 44
(Cumulenes and Allenes). (m) Ogasawara, M. Tetrahedron: Asymmetry
2009, 20, 259.
(8) For the transition state of C-H insertion, see: (a) Dobson, R. C.;
Hayes, D. M.; Hoffmann, R. J. Am. Chem. Soc. 1971, 93, 6188. (b) Bodor,
N.; Dewar, M. J. S.; Wasson, J. S. J. Am. Chem. Soc. 1972, 94, 9095. (c) Jug,
K.; Mishra, P. C. Int. J. Quantum Chem. 1983, 23, 887. (d) Taber, D. F.;
Meagley, R. P.; Doren, D. J. J. Org. Chem. 1996, 61, 5723.
(9) (a) Wolinsky, J.; Clark, G. W.; Thorstenson, P. C. J. Org. Chem. 1971,
41, 745. (b) Gilbert, J. C.; Giamalva, D. H.; Weerasooriya, U. J. Org. Chem.
1983, 48, 5251. (c) Gilbert, J. C.; Blackburn, B. K. J. Org. Chem. 1986, 51,
3656. (d) Karpf, M.; Dreiding, A. S. Helv. Chim. Acta 1979, 62, 852.
(e) Karpf, M.; Huguet, J.; Dreiding, A. S. Helv. Chim. Acta 1982, 65, 13.
(10) The observed selectivity can be ascribed to the differences in bond
dissociation energies of the various C-H bonds. For a review see: Benson,
S. W. J. Chem. Educ. 1965, 42, 502.
(11) (a) Gilbert, J. C.; Giamalva, D. H.; Baze, M. E. J. Org. Chem. 1985,
50, 2557. (b) Adams, J.; Poupart, M.-A.; Grenier, L.; Schaller, C.; Ouimet,
N.; Frenette, R. Tetrahedron Lett. 1989, 30, 1749. (c) Taber, D. F.; Christos,
T. E. Tetrahedron Lett. 1997, 38, 4927. (d) Davis, H. M. L.; Beckwith,
R. E. J.; Antoulinakis, E. G.; Jin, Q. J. Org. Chem. 2003, 68, 6126. For recent
reviews on C-H functionalization, see: (e) Davis, H. M. L.; Manning, J. R.
Nature 2008, 451, 417. (f) Davis, H. M. L.; Nikolai, J. Org. Biomol. Chem.
2005, 3, 4176.
(12) (a) Wang, J.; et al. Nature 2006, 441, 358. (b) Singh, S. B.; Jayasuriya,
H.; Ondeyka, J. G.; Herath, K. B.; Zhang, C.; Zink, D. L.; Tsou, N. N.; Ball,
R. G.; Basilio, A.; Genilloud, O.; Diez, M. T.; Vicente, F.; Pelaez, F.; Young,
K.; Wang, J. J. Am. Chem. Soc. 2006, 128, 11916.
(15) For reviews of allenic structures on natural products, see: (a) Krause,
€
N.; Hoffmann-Roder, A. Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; p 997. (b) Hoffmann-
€
Roder, A.; Krause, N. Angew. Chem., Int. Ed. 2004, 43, 1196.
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lithium trimethylsilydiazomethane (2): C-H insertion in
structurally biased systems, and the selectivity between
C-H insertion and allene formation. This systematic study
revealed a profound impact of electronic, conformational,
steric, and stereoelectronic effects on the regioselectivity in
C-H insertion as well as the chemoselectivity between C-H
insertion vs allenylsilane formation. Also, the unprecedented
reaction of alkylidene carbene with trimethylsilyldizo-
methane (1) was systematically investigated to prove its
generality as a new method for the efficient synthesis of
allenylsilanes.
TABLE 1. Electronic Effect on C-H Insertion Selectivitya
Results and Discussion
Alkylidene carbenes are highly electrophilic species, and
thus readily react with available electron sources including σ-
electrons in C-H,1 O-H,17 N-H,18 C-Si,19 and O-Si20
bonds and π-electrons in CdC bonds.4,5 Despite their high
reactivity, generally good to excellent chemo- and regios-
electivity as well as stereoselectivity have been observed in
their reactions. A powerful electronic influence by hetero-
atom substituents such as oxygen and nitrogen is well-known
in carbene-mediated C-H insertion, yet the heteroatom
effect is either reinforced or canceled out by structural or
conformational bias in certain substrates. To gain further
insight into the factors that interplay to provide these
observed selectivity profiles, we explored systems that con-
tain more than two competing C-H bonds on cyclic and
acyclic systems with electronically, conformationally, and
sterically differentiated environments. We envision that
deconvolution and delineation of individual contributions
of these factors would provide more elaborated information
on carbene insertion reactions.
Electronic Effect. The regioselectivity of C-H insertion
was examined by probing the contribution of an electronic
effect. Especially, the extent of the activating role of an
oxygen substituent to the C-H bonds on the same carbon
bearing the oxygen was systematically explored (Table 1).
First, the carbene insertion into an activated C-Ha and
normal C-Hb on a linear ketone substrate 4a provided a
mixture of 5a and 6a in a 91:9 ratio and 96% yield (entry 1).
Moving the activating oxygen from the terminal carbon to an
aReaction conditions: TMSCHN2 (1.6 equiv), n-BuLi(1.7 equiv), -78
°C to room temperature in THF over 3 h.
internal carbon of substrate 4b, such that the oxygen be-
comes an endo in the incipient ring, further activates the
C-Ha for insertion, affording exclusively 5b (entry 2). We
surmise that the smaller C-O-C bond angle in 4b relative to
that of C-C-C in 4a facilitates a carbene intermediate to
interact with the C-Ha bond to form a lower energy transi-
tion state than that with C-Hb.21 The extent of the activating
role of the two different oxygens was explored with sub-
strates 4c-f where the electronic nature of the substituents
on the oxygen connected to the carbon bearing C-Hb was
varied while that of C-Ha remained constant as benzyl ether
(entries 3-6). The selectivity trend between 5c-f and 6c-f
clearly suggests that the influence of the endo oxygen is
slightly larger than that of the exo oxygen if the alkyl group
is attached to the oxygen (entry 3), reconfirming the observed
selectivity trend with substrates 4a and 4b. However,
the extent of contribution by the endo oxygen diminished
(16) For recent examples for allene synthesis, see: (a) Pu, X.; Ready, J. M.
J. Am. Chem. Soc. 2008, 130, 10874. (b) Zhang, W.; Xu, H.; Xu, H.; Tang, W.
J. Am. Chem. Soc. 2009, 131, 3832. (c) Ogasawara, M.; Okada, A.; Nakajima,
K.; Takahashi, T. Org. Lett. 2009, 11, 177. (d) Zeng, X.; Frey, G. D.; Kousar,
S.; Bertrand, G. Chem.;Eur. J. 2009, 15, 3056. (e) Maity, P.; Lepore, S. D.
J. Am. Chem. Soc. 2009, 131, 4196. (f) Li, J.; Kong, W.; Fu, C.; Ma, S. J. Org.
Chem. 2009, 74, 5104. (g) Zheng, Z.-J.; Shu, X.-Z.; Ji, K.-G.; Zhao, S.-C.;
Liang, Y.-M. Org. Lett. 2009, 11, 3214. (h) Lee, D.; Danishefsky, S. J. Am.
€
ꢀ
Chem. Soc. 2010, 132, 4427. (i) Furstner, A.; Mendez, M. Angew. Chem., Int.
Ed. 2003, 42, 5355. (j) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118,
ꢀ
ꢀ
4492. (k) Gonzalez, J. R.; Gonzalez, A. Z.; Soderquist, J. A. J. Am. Chem.
Soc. 2009, 131, 9924. (l) Sakai, T.; Danheiser, R. L. J. Am. Chem. Soc. 2010,
132, 13203.
(17) For an example of O-H insertion, see: Kim, S.; Yoon, K.-Y.; Cho,
C. M. Chem. Commun. 1996, 909.
(18) For selected examples of N-H insertion, see: (a) Miyagi, T.;
Aoyama, T.; Shioiri, T. Synlett 1997, 1063. (b) Miyagi, T.; Hari, Y.; Shioiri,
T. Tetrahedron. Lett 2004, 45, 6303. (c) Taber, D. F.; Plepys, R. A. Tetra-
hedron. Lett 2005, 46, 6045.
(19) For an example of C-Si insertion, see: Li, J.; Sun, C.; Lee, D. J. Am.
Chem. Soc. 2010, 132, 6640.
(20) For selected examples of O-Si insertion, see: (a) Feldman, K. S.;
Wrobleski, M. L. Org. Lett. 2000, 2, 2603. (b) Feldman, K. S.; Wrobleski,
M. L. J. Org. Chem. 2000, 65, 8659. (c) Hari, Y.; Kondo, R.; Date, K.;
Aoyama, T. Tetrahedron 2009, 65, 8708. (d) Kim, S.; Cho, C. M. Tetrahedron
Lett. 1995, 36, 4845.
(21) This can be considered as a Thorp-Ingold effect induced by the two
lone-pair electrons of oxygen. For a review and leading references for the
Thorpe-Ingold effect, see: (a) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105,
1735. (b) Lightstone, F. C.; Bruice, T. C. J. Am. Chem. Soc. 1994, 116, 10789.
(c) Allinger, N. L.; Zalkow, V. J. Org. Chem. 1960, 25, 701. (d) Bruice, T. C.;
Pandit, U. K. J. Am. Chem. Soc. 1960, 82, 5858. (e) Bruice, T. C.; Pandit,
U. K. Proc. Natl. Acad. Sci. U.S.A. 1960, 46, 402. (f) Ingold, C. K.; Sako, S.;
Thorpe, J. F. J. Chem. Soc. 1922, 121, 1117. (g) Ingold, C. K. J. Chem. Soc.
1921, 119, 305. (h) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. J. Chem. Soc.
1915, 107, 1080.
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TABLE 2. Conformational Effect on C-H Insertion Selectivitya
proportionally to the change from an electron-donating
ethyl (entry 3) to an inductively electron-withdrawing vinyl
(entry 4), ethynyl (entry 5), and methoxy (entry 6) group,
ultimately providing the reversed selectivity of a 33:67 ratio
for 5f:6f compared to a 66:33 ratio for 5c:6c. Unexpectedly,
only the inductive effect of the R-substituents, but not their
resonance effect through the participation of π- or lone-pair
electrons, seems to contribute to the reactivity of the C-Hb
bond, otherwise the proportion of 6c-f should have in-
creased relative to that of 6c. β-Branched substrates contain-
ing different protecting groups on the oxygen 4g and 4h
showed identical selectivity, generating a mixture of 5g:6g
and 5h:6h both in 88:12 ratios (entries 7 and 8). On the other
hand, conformationally constrained substrate 4i with almost
identical electronic bias to that of 4g and 4h afforded much
higher selectivity, generating only 5i albeit the yield was
slightly lower (entry 9). The higher activating effect of the
endo oxygen in R-branched substrates 4j and 4k relative to
β-branched substrates 4g and 4h, where the oxygen is an exo
to an incipient ring, was clearly demonstrated by the perfect
selectivity for the formation of 5j and 5k over 6j and 6k,
respectively (entries 10 and 11).
Conformational Effect. To explore the conformational
effect on the regioselectivity of C-H insertion, we prepared
substrates containing a pyran ring and a linear side chain that
has at least two competing cyclic and acyclic C-Hγ bonds
available toward carbene insertion (Table 2). The selectivity
of insertion into C-Ha vs C-Hb should be the consequence
of respective conformational behaviors of cyclic and acyclic
portions of these molecules. The pyran substrate 4l bearing a
side chain where oxygen is exo to an incipient ring gave a
mixture of 5l and 6l in a 5:95 ratio, where preferred insertion
occurred into an acyclic C-Hb over cyclic C-Ha bond (entry
1). Replacing the benzyl-protecting group in 4l with an
electron-withdrawing pivalate in 4m completely switched
the insertion preference, generating C-Ha insertion product
5m as the only observed product (entry 2). For comparison,
the insertion reaction with substrate 4n that does not contain
any oxygen substituent afforded a mixture of 5n and 6n in a
16:84 ratio. This clearly indicates two important features: (1)
the C-Ha on a conformationally rigid cyclohexane ring is
less reactive than the C-Hb in the butyl group and (2) the
extent of an activating role of an oxygen substituent is more
pronounced in acyclic environments than in conformation-
ally rigid systems, otherwise a similar ratio of products
should have been observed from both 4l and 4n. The
complete reversal of selectivity with 4m also suggests that
the conformational contribution should be subtle so that it
could be easily overridden by an electronic factor.
Next, we examined a ring-size effect on the regioselectivity
of insertion. We expected that C-H bonds on five- and six-
membered rings would have a slightly different reaction rate
as the reflection of subtle difference in their conformational
behavior. However, the insertion reaction of substrate 4o
containing C-Hγ bonds on both six- and five-membered
rings occurred at the C-Hb on the five-membered ring over
C-Ha on the six-membered ring with remarkable selectivity
of a 2:98 ratio for 5o:6o in 69% combined yield (entry 4). A
complete regioselectivity of insertion was observed with
substrate 4p and 4q, where the oxygen substituent is endo
to the incipient ring as opposed to exo in substrate 4l,
provided 6p and 6q over 5p and 5q (entries 5 and 6).
aReaction conditions: TMSCHN2 (1.6 equiv), n-BuLi(1.7 equiv), -78 °C
to room temperature in THF over 3 h. bCombined yield including 14%
of allene product.
This result is consistent with the high selectivity with sub-
strate 4b (entry 2 in Table 1), where the smaller C-O-C
bond angle relative to that of C-C-C seems to be a key
structural element.21 To our surprise, even the unactivated
acyclic C-Hb bond in 4r appeared to be slightly more
reactive than the seemingly more activated cyclic C-Ha
bond by an oxygen substituent, affording a mixture of 5r
and 6r in a 42:58 ratio (entry 7). This is another evidence that
the electronic contribution of oxygen in conformationally
rigid environment is diminished. The C-Ha bond on the
epoxide moiety of 4s is virtually unreactive toward carbene
insertion, affording only 6s. This is the result of not only a
larger bond angle between the C-Ha and the C-C bond
tethered to the carbene moiety but also stronger bond
strength of the C-Ha bond due to an increased s-character
of the exocyclic bond on the three-membered ring.22
Steric Effect. Various selectivities (chemo-, regio-, stereo-)
in organic transformations are generally the consequence of
interplay between electronic and steric effects. We already
demonstrated the fundamentally important role of electronic
and conformational/structural effects in Tables 1 and 2. The
C-H insertion selectivity modulated by an electronic factor
(22) Tian, Z.; Fattahi, A.; Lis, L.; Kass, S. R. J. Am. Chem. Soc. 2006, 128,
17087.
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TABLE 3. Steric Effect for Selectivity on C-H Insertiona
aReaction conditions: TMSCHN2 (1.6 equiv), n-BuLi(1.7 equiv), -78 °C to room temperature in THF over 3 h.
on or near the reacting C-H stems from the strongly
electron-deficient nature of the reacting counterpart car-
bene. At this juncture, we were intrigued by the potential
influence of steric factor for the selectivity. Because of the
sterically unencumbered nature of the alkylidene carbene
center, we predict that the effect of steric hindrance on and
around the C-H bond undergoing insertion would be less
important compared to that of the electronic effect, which,
however, should not be neglected. To assess the contribution
of steric effect to the regioselectivity of C-H insertion, a
range of substrates containing at least two competing C-H
bonds with sterically differentiated environments were ex-
amined (Table 3). First, the insertion into tertiary C-H
bonds on cyclic and acyclic environments was compared
with substrate 4t, affording a mixture of 5t and 6t in a 42:58
ratio (entry 1). Coincidently, a mixture of 5u and 6u with an
identical ratio was also observed from the reaction of sub-
strate 4u containing two tertiary C-H bonds on five- and six-
membered rings (entry 2). On the other hand, identical
substrate 4u0 but with a 4-tertiary butyl substituent gave a
slightly increased ratio (33:67) between 5u0 and 6u0 (entry 3).
Substrate 4v with two competing C-H bonds on cyclohexyl
and 4-tertiary butyl-substituted cyclohexyl moieties showed
similar insertion behavior, affording a 45:55 ratio of 5v:6v
(entry 4). These results strongly support the general reactiv-
ity trend that C-H bonds in more conformationally rigid
environments are slightly less reactive than those in more
flexible situations. The first example of steric hindrance
meaningfully discriminating C-H insertion was illustrated
by the substrate 4w where equatorial and axial C-H bonds
compete (entry 5). As expected, insertion into the sterically
less hindered equatorial C-Hb was slightly favored over
C-Ha, generating a 42:58 mixture of 5w and 6w. In the case
of 4x, more favorable insertion into a secondary C-Hb over
a tertiary C-Ha in a 40:60 ratio was observed (entry 6). This
is somewhat unusual because the electronic contribution
seems to be far greater that that of steric hindrance for the
carbene insertion process and thus 3° C-Ha was expected be
more reactive than 2° C-Hb. Although this observed selec-
tivity could be the consequence of steric hindrance-based
control more data need to be accumulated to generalize this
argument. The insertion reaction of substrate 4y that is
similar to 4w but containing an isopropyl group near the
axial C-Ha bond showed significantly increased selectivity
for the insertion into sterically less hindered C-Hb, afford-
ing a mixture of 5y and 6y in a 26:74 ratio (entry 7). When the
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insertion into two axial C-Ha and C-Hb bonds competes in
substrate 4z, a reduced yet appreciable selectivity between 5z
and 6z was observed (entry 8).
axial hydrogens should take place selectively at (C)C-Hb
over the (O)C-Ha bond to generate product 10. In this case,
due to poor orbital overlap, electron delocalization via
n(O) f σ*(C-H) will be minimal, and thus the oxygen
would deactivate the (O)C-Ha bond through an inductive
effect.13a,24
From the insertion behavior of substrates 4t-z, an ob-
vious selectivity trend has emerged: steric hindrance does
affect the selectivity of carbene insertion by retarding the
insertion into C-H bonds in sterically more congested
environment but its contribution was found to be marginal.
Steroelectronic Effect. The diminished electronic contri-
bution by oxygen when constrained in a cyclic structure, for
example 4l and 4r in Table 2, implies that the directionality of
its lone pair electrons relative to a C-H bond undergoing
insertion reaction should be important. The electronic effect
of the oxygen substituent in the C-H insertion reaction of
alkylidene carbenes8a is expected to be manifested by the
specific interactions of orbitals around the reaction center.23
The most important orbital-orbital interaction was hy-
pothesized to be the axially oriented nonbonding orbital
of oxygen and the σ* orbital of the axial C-Ha bond
(Scheme 2). We reasoned that if this stereoelectronic effect of
an oxygen substituent is important, the C-H insertion of
carbene 7 should generate product 8 via a selective insertion
into the axial (O)C-Ha bond due to its more electron-rich
nature resulting from n(O) f σ*(C-Ha) electron delocaliza-
tion. On the other hand, the insertion of carbene 9 lacking
To test this stereoelectronic hypothesis for regioselective
C-H insertion, we prepared two pairs of conformationally
constrained diastereomers 11a/11b and 11c/11d that repre-
sent the insertion behavior of 7 and 9, respectively (Table 4).
Indeed, substrate 11a underwent a selective insertion into the
C-Ha bond, providing 12a as the only insertion product
when condition A (1.6 equiv of n-BuLi/1.7 equiv of TMS-
diazomethane/THF/-78 °C, 0.06 M) was employed (entry
1). However, to our surprise a significant amount of another
product was obtained, which was found not to be the
expected regioisomer but allenylsilane 14a (see Table 4 for
mechanistic rationale). On the other hand, 11b, a diastereo-
mer of 11a, afforded a mixture of 12b and 13b in a 1:11 ratio
together with allenylsilane 14b (entry 2). Similarly, reaction
of substrates 11c and 11d that contain only equatorial
hydrogens afforded a mixture of products 12c and 13c in
1:5 ratio and only insertion product 13d, respectively, ac-
companied by allenylsilane 14c and 14d (entries 3 and 4). The
predominant or exclusive formation of 13b and 13d via the
insertion into seemingly less reactive C-Hb compared to
C-Ha should be the consequence of the stereoelectronic
effect of oxygen substituent as hypothesized in Scheme 2.
The formation of allenylsilane byproducts 14a-d via a
competing intermolecular process is attributed to somewhat
lower reactivity of C-H bonds in these systems, which
further support the general trend that C-H bonds in con-
formationally rigid environments are less reactive than those
corresponding flexible systems. We surmised that by increas-
ing the reaction concentration, allenylsilane formation
should be more favorable because the intermolecular reac-
tion rate would increase while the intramolecular reaction
rate remains constant. Indeed, under condition B (2 equiv of
SCHEME 2
TABLE 4. Stereoelectronic Effect for Selectivity on C-H Insertiona
aCondition A: Reaction conditions: TMSCHN2 (1.6 equiv), n-BuLi(1.7 equiv), -78 °C to room temperature in THF over 3 h. Condition B:
TMSCHN2 (3 equiv), n-BuLi (2 equiv), -78 °C to room temperature in THF over 1 h then additional 2 h at room temperature.
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TABLE 5. Optimization for Allenylsilane Formationa
SCHEME 3
aCombined yield including 8% of regioisomer 6a.
SCHEME 4. Putative Mechanisms for Allenylsilane Formation
aReactions were carried out in THF. bDetermined by 1H NMR. cEt2O
as the solvent. dAlmost identical result in hexane. eQuenched with D2O.
n-BuLi/3.0 equiv of TMS-diazomethane/THF/-78 °C, 0.06
M), the formation of allenylsilane becomes a major reaction
pathway, producing allenylsilanes 14a-d predominantly.
Optimization for Allenylsilane Formation. To gain more
insight into the mechanism of the allene formation as well as
to develop an optimal protocol for its formation, systematic
variation on stoichiometry and concentration was examined
(Table 5). Considering the bimolecular nature for the for-
mation of allenylsilane, we envisioned that the relative
portion of unimolecular C-H insertion could be decreased
upon increasing the concentration of reaction and by em-
ploying excess amounts of 1 or 2. As expected, at higher
reaction concentration, an increased amount of allenylsilane
14c with concomitant decrease of 13c (entries 1 vs 2 and 3 vs
4) was obtained.25 A maximum yield of 14c (75%) was
realized when a 3-fold excess of 1 was employed at 0.06 M
(entry 4) but at a higher concentration deteriorated yield was
observed (entry 5). Increasing the amount of 2 also lowered
the yield (entry 7). Also, a significant solvent effect was not
observed, thus changing the solvent from THF to Et2O did
not affect the yield or product ratio.26
Having recognized the profound impact of concentration
and stoichiometry of reagents on the selectivity, we resub-
jected substrates 11a-d to the optimized reaction conditions
(condition B) for allenylsilane formation (Table 4). Substrate
11a containing the stereoelectronically activated axial C-H
bond afforded a 33:67 ratio of 12a:14a. In contrast, sub-
strates 11b-d lacking axial C-H bonds provided an in-
creased amount of allene in 25:75, 8:92, and 8:92 ratios of
13b:14b, 13c:14c, and 13d:14d. For comparison, we reexa-
mined acyclic ketone substrates 4a and 4b under the opti-
mized conditions for allene formation (Scheme 3). In
contrast to the reactivity pattern of pyran substrates
11a-d, acyclic ketones 4a and 4b did not generate allenes
15 and 16 at all. This is most likely the consequence of a faster
C-H insertion that preempts the relatively slower bimole-
cular process leading to allene formation.
Mechanistic Considerations. The reaction between ketone
17 and lithium trimethylsilyldiazomethane 2 followed by
Peterson olefination and nitrogen extrusion would generate
alkylidene carbenes 18.27 Once generated, 18 undergoes
rapid C-H insertion to form cyclopentene derivative 19
(Scheme 4). However, we surmised that if the insertion into
a C-H bond becomes slower or not available, an intermo-
lecular process starts to operate. In this scenario, the parti-
cipation of 2 to generate adduct 20 (path A) seems most
probable by analogy to the reaction between an alkylidene
carbenoid and Grignard reagents as reported by Satoh and
co-workers.28,29 Upon formation, the extrusion of N2 from
vinyl lithium 20 via 21 would generate allenyllithium species
22, the protonation of which would afford allenylsilane 23.
Likewise, the reaction of alkylidene carbene 18 with free
trimethylsilyldiazomethane 1 will form adduct 24 (path B),
the N2 elimination of which would result in the formation of
(23) (a) Deslongchamps, P. Stereoelectronic Effects in Organic Chemistry;
Pergamon Press: New York, 1995. (b) Malatesta, V.; Ingold, K. U. J. Am.
Chem. Soc. 1981, 103, 609.
(24) Wang, J.; Stefane, B.; Jaber, D.; Smith, J. A. I.; Vickery, C.; Diop,
M.; Sintim, H. O. Angew. Chem., Int. Ed. 2010, 49, 3964.
(25) Selectivity control by changing reaction concentration was demon-
strated in olefin metathesis reactions: Maifeld, S. V.; Miller, R. L.; Lee, D.
J. Am. Chem. Soc. 2004, 126, 12228.
(27) (a) Colvin, E. W.; Hamill, B. J. J. Chem. Soc., Chem. Commun. 1973,
151. (b) Ohira, S.; Ishi, S.; Shinohara, K.; Nozaki, H. Tetrahedron Lett. 1990,
31, 1039. (c) Ohira, S.; Okai, K.; Moritani, T. J. Chem. Soc., Chem. Commun.
1992, 721. (d) Taber, D. F.; Walter, R.; Meagley, R. P. J. Org. Chem. 1994,
59, 6014. (e) Sakai, A.; Aoyama, T.; Shioiri, T. Tetrahedron 1999, 55, 3687.
(28) Satoh, T. Chem. Soc. Rev. 2007, 36, 1561.
(29) Related examples of Path B: (a) Satoh, T.; Sakamoto, T.; Watanabe,
M. Tetrahedron Lett. 2002, 43, 2043. (b) Satoh, T.; Sakamoto, T.; Watanabe,
M.; Takano, K. Chem. Pharm. Bull. 2003, 51, 966.
(26) Instead of free carbene, a protocol that involves carbenoid formation
was also examined but the ratio remained unchanged.
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TABLE 7. Allenylsilanes from Functinalized Acyclic Ketonesa
TABLE 6. Allenylsilane Synthesis from Acyclic Ketonesa
aConditions: TMSCHN2 (3 equiv), n-BuLi (2 equiv), -78 °C to room
temperature in THF over 1 h then additional 2 h at room temperature.
bSubstrates with existing stereocehhmistry accorded ca. 1:1 ratio of
diastereomers.
aConditions: TMSCHN2 (3 equiv), n-BuLi (2 equiv), -78 °C to room
temperature in THF over 1 h then additional 2 h at room temperature.
aromatic C-H insertion or addition is possible,30 only
allenylsilane 25d was obtained in good yield. However,
butyl-substituted ketone 24e provided a mixture of 25e and
25e0 in 80% yield with 0.25:1 ratio (entry 5). Increasing the
concentration to 0.10 M changed the ratio to 0.33:1.
Although the ratio was further changed to 1.1:1 at higher
concentration (0.20 M) the yield decreased. This series of
experiments implies that the insertion into 2° C-Hγ in 24e
should be substantially more favorable than that of 1° C-Hγ
in 24c because under similar conditions no insertion but only
allene formation was observed. To further explore how
substrate structure and reaction concentration affect the
ratio of products, we examined the behavior of adamen-
tane-derived ketone 24f carrying multiple 2° C-Hγ bonds
available for insertion (entry 6). Under dilute conditions with
1:2:2 ratio of 24f:BuLi:1, insertion product 25f0 was obtained
predominantly over allenylsilane 25f. However, at an in-
creased concentration with the typical 1:2:3 ratio of 24f:
BuLi:1, the allenylsilane formation favorably competed with
the insertion into a 2° C-Hγ bond, thereby providing the
ratio of 25f:25f0 in the range of 1:1 to 3.3:1 with good yield.
allenylsilane 23. We observed that increasing the amount of
free trimethylsilyldiazomethane 1, but its lithated form 2,
provided proportinally increased amounts of allenylsilane
14c, but with 2, the yield was increased only slightly (Table 5,
entries 3 vs 7). On the basis of this observation, we tentatively
concluded that path B is a major-contributing pathway and
path A, if it is still operating, is a minor reaction pathway.
Interestingly, quenching the reaction with D2O did not give
an appreciable amount of deuterated allenylsilane (Table 5,
entry 7), which also makes our mechanistic interpretation
inconclusive.
Reaction Scope. Under the optimized conditions for alle-
nylsilane formation, we examined substrate scope and reac-
tion efficiency (Table 6). Unbranched substrates 24a-d
carrying methyl, ethyl, propyl, and phenethyl groups af-
forded allenylsilanes 25a-d in good yields (entries 1-4). It
was somewhat surprising that substrate 24c that contains 1°
C-Hγ bonds available for insertion still gave allenylsilane
25c exclusively. For 1,3-dibenzyl acetone 24d, although the
(30) Ogawa, H.; Aoyama, T.; Shioiri, T. Synlett 1994, 757.
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TABLE 8. Allenylsilane Formation from Cyclic Ketonesa
b
aReaction conditions: TMSCHN2 (3 equiv), n-BuLi (2 equiv), -78 °C to room temperature in THF over 2 h. at room temperature. Recovered
starting meterial in 40% yield. cMostly ring-expansion products formed. dInsertion product was isolated in 17% yield.
Another adamentane-derived substrate 24g that has 3°
C-Hγ bonds available for insertion afforded insertion pro-
duct 25g0 without an appreciable amount of allenylsilane 25g
(entry 7). On the other hand, 24h, a simplified version of 24g
that contains only a single cyclohexane ring with 2° C-Hγ
bonds behaved somewhat similar to 24f such that a mixture
of allenylsilane 25h and insertion product 25h0 were gener-
ated, but at higher concentration allene formation becomes a
predominant process (entry 8).
Next, we examined substrates containing a carbon or an
oxygen branch either at the R-, β-, or γ-position (Table 7).
Reactions with substrates 26a-f consistently provided alle-
nylsilanes 27a-f in the range of 60-75% yield except for
26g. Various oxygen functionalities such as ether, ester,
acetal, and epoxide did not interfere with the formation of
allenylsilanes. However, a significant influence of certain
functionality was recognized. For example, the reaction of
26f carrying a γ,δ-epoxide afforded only allenylsilane 27f
(entry 6), whereas 26g with the corresponding dioxolane
moiety yielded C-Hγ insertion product 27g0 predominantly
together with allenylsilane 27g only in 6% yield in all three
concentrations examined (entry 7). On the other hand, a
dioxane-containing susbtrate 26h provided a mixture of
allenylsilane 27h and insertion product 27h0 in a 1.9:1 ratio
(entry 8). This indicates that a subtle environmental differ-
ence at or around C-H bonds can affect their reactivity
whereby a completely different chemo- and regioselectivity
may ensue.22,31
We expected that cyclic ketones of small- to medium-sized
rings should be excellent substrates for allenylsilane forma-
tion32 since the competing C-H insertion process will be
excluded (Table 8). As expected, cyclopentanone 28a and
dihydrocarvone 28b afforded allene 29a (55%) and 29b
(60%), respectively, in moderate yields (entries 1 and 2).
Substrate 28c containing acyclic ketone gave corresponding
bisallene 29c as a mixture of four stereoisomers in 51% yield
when an excess amount of reagents (3 equiv of BuLi and 5
equiv of 1) was used (entry 3). The formation of allene has
proven inherently sensitive to the steric encumbrance at the
R-carbon of cyclic ketones, as evidenced by the low yield of
menthone 28d (entry 4) and R-substituted cycloheptanones
28g and 28h (entries 7 and 8). On the other hand, cyclopen-
tanone 28e and its derivative 28f afforded the correspond-
ing allenes 29e and 29f in respectable yields (entries 5 and 6).
(31) This is probably due to the difference of strength of C-H bonds on 3-
and 5-membered rings. Alternatively, the more favourable n(O)fσ*(C-H)
electron delocalization in dioxolane may also cause this difference as
described in ref 13a.
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The low yields of allenylsilanes from these R-substituted
ketones seem to stem from the slow elimination of LiOSiMe3
from the intermediate formed between the ketone and
lithium trimethylsilyldiazomethane 2. In contrast, other
cyclic ketones 28i-l not possessing bulky substituents at the
R-carbon gave allenylsilanes 29i-l in good to excellent
yields. It is quite surprising that there was no C-H insertion
product from the 12-membered-ring ketone 28k as opposed
to the 15-membered-ring ketone 28l, which afforded a 2.5:1
mixture of allenylsilane 29l and C-H insertion product in
60% overall yield.
reactivity of alkylidene carbenes toward trimethylsilyldiazo-
methane, we have developed a unique method for the synth-
esis of silyl-functionalized trisubstituted allenes.
The selectivity between the C-H insertion and allenylsi-
lane formation observed in this study provides further in-
sight into the relative reactivity of particular C-H bonds
toward insertion by alkylidene carbenes. We expected that
the reactivity and selectivity trends of various C-H bonds
toward alkylidene carbenes discovered in this study will be
extrapolated to other types of carbene- and carbenoid- as
well as nitrene- and nitrenoid-mediated insertion processes.
Conclusions
Experimental Section
We have examined the regioselectivity of alkylidene car-
bene-mediated C-H insertion utilizing electronic, confor-
mational, steric, and stereoelectronic effects. Due to a
significant rate difference caused by these factors, high regio-
and chemoselectivity between C-H bonds in different en-
vironments could be obtained. It is well-known that the
C-H bond connected to the same carbon bearing an ether
oxygen substituent is significantly more reactive toward
C-H insertion. However, in this study, we have observed
that the lone-pair electrons of oxygen can either activate a
C-H bond via an n(O) f σ*(C-H) resonance effect or
deactivate it via an inductive effect by the strong electro-
negativity of oxygen depending on their relative orientation
to the C-H bonds.
General Information. All reactions were run under an atmo-
sphere of nitrogen, unless otherwise indicated. Flasks were
oven-dried overnight and cooled under a stream of nitrogen.
Solvents were purified based on standard procedures. Flash
˚
chromatography was performed with silica gel 60 A (32-63
mesh). Analytical thin layer chromatography (TLC) was per-
formed on glass plates coated with silica gel 60 (particle size
0.040-0.063 mm). 1H NMR and 13C NMR spectra were
1
recorded in the deuterated solvents stated. H and 13C che-
mical shifts were referenced to internal solvent resonances
and reported relative to SiMe4; multiplicities are indicated by
s (singlet), d (doublet), t (triplet), q (quartet), qn (quintet),
m (multiplet), and br (broad). Coupling constants, J, are
reported in hertz. Characterization data for compounds
4a-k, 5a-k, 6a-k, 11a-d, 12a-c, 13b-d, 14a-d were pre-
viously reported.13a
We recognized that when an intramolecular C-H inser-
tion of alkylidene carbenes is slow, an intermolecular reac-
tion between the alkylidene carbene and free trimethylsily-
ldiazomethane supersedes the insertion, leading to the for-
mation of allenylsilanes. Because of its bimolecular nature,
higher efficiency of allenylsilane formation was realized by
running the reaction at higher concentration as well as
slowing down the competing C-H insertion with conforma-
tional and stereoelectronic effects. We also found that in
general, conformationally constrained C-H bonds are less
reactive than those in acyclic environments. Thus, insertion
reaction of substrates containing these conformationally
constrained C-H bonds was accompanied by the formation
of allenylsilanes. Similarly, the allene formation is more
favorable than insertion into 1° C-H bonds, providing
exclusively allenylsilane. On the other hand, the competition
between allene formation and insertion into acyclic 2° and 3°
C-H bonds predominantly gives insertion products. Relying
on this differential and controllable reactivity of C-H bonds
toward alkylidene carbenes as well as an unprecedented
Typical Preparative Scale Reaction for C-H Insertion. To a
solution of trimethylsilyldiazomethane (2.0 M in Et2O, 0.19 mL,
0.38 mmol) in 10 mL of THF was added n-BuLi (2.5 M in
hexanes, 0.16 mL, 0.4 mmol) at -78 °C. After the solution was
stirred for 30 min, a substrate (0.25 mmol) in 2 mL of THF was
added. The mixture was stirred for 1 h at -78 °C and gradually
warmed to room temperature over 2 h. The reaction mixture was
quenched by adding a few drops of water and filtered through a
pad of silica gel. The filtrate was concentrated and the residue
was flash chromatographed on silica gel.
Typical Preparative Scale Reaction for Allenylsilane. To a
solution of trimethylsilyldiazomethane (2.0 M in Et2O, 0.75 mL,
1.5 mmol, 3.0 equiv) in 6.0 mL of THF was added n-BuLi (2.5 M
in hexanes, 0.4 mL, 1.0 mmol, 2.0 equiv) at -78 °C. After the
mixture was stirred for 30 min, a substrate (0.5 mmol) in 1.0 mL
of THF was added. The mixture was stirred for 1 h at -78 °C,
then gradually warmed to room temperature over 1 h. The
reaction mixture was stirred an additional 2 h at room tempera-
ture and quenched by filtering through a pad of silica gel. The
filtrate was concentrated and the residue was flash chromato-
graphed on silica gel.
4l: 1H NMR (500 MHz, CDCl3) δ 7.35 (m, 5H), 4.43 (s, 2H),
3.63 (dd, J=12, 4.5 Hz, 1H), 3.46 (t, J=6 Hz, 2H), 3.28 (dd, J=
12, 9.5 Hz, 1H), 2.50 (t, J=7.5 Hz, 2H), 2.32 (ABX, JAB=7 Hz,
(32) For other representative examples of allenylsilane synthesis and their
use in organic synthesis, see: (a) Borzilleri, R. M.; Weinreb, S. M.; Parvez, M.
J. Am. Chem. Soc. 1994, 116, 9789. (b) Masse, C. E.; Panek, J. S. Chem. Rev.
1995, 95, 1293. (c) Suginome, M.; Matsumoto, A.; Ito, Y. J. Org. Chem. 1996,
61, 4884. (d) Jin, J.; Weinreb, S. M. J. Am. Chem. Soc. 1997, 119, 5773.
(e) Shepard, M. S.; Carreira, E. M. J. Am. Chem. Soc. 1997, 119, 2597.
(f) Hirashima, S.; Aoyagi, S.; Kibayashi, C. J. Am. Chem. Soc. 1999, 121,
9873. (g) Marshall, J. A.; Maxson, K. J. Org. Chem. 2000, 65, 630. (h) Han,
J. W.; Tokunaga, N.; Hayashi, T. J. Am. Chem. Soc. 2001, 123, 12915.
(i) Evans, D. A.; Sweeney, J. K.; Rovis, T.; Tedrow, J. S. J. Am. Chem. Soc.
2001, 123, 12095. (j) Shen, Q.; Hammond, G. B. J. Am. Chem. Soc. 2002, 124,
6534. (k) Heo, J.-N.; Micalizio, G. C.; Roush, W. R. Org. Lett. 2003, 5, 1693.
(l) Daidouji, K.; Fuchibe, K.; Akiyama, T. Org. Lett. 2005, 7, 1051. (m) Wipf,
P.; Pierce, J. G. Org. Lett. 2005, 7, 3537. (n) Gonzalez, A. Z.; Soderquist, J. A.
Org. Lett. 2007, 9, 1081. (o) Ohmiya, H.; Ito, H.; Sawamura, M. Org. Lett.
2009, 11, 5618. (p) Brawn, R. A.; Panek, J. S. Org. Lett. 2009, 11, 4362.
(q) Nishimura, T.; Makino, H.; Nagaosa, M.; Hayashi, T. J. Am. Chem. Soc.
2010, 132, 12865.
J
AX=9 Hz, JBX=9.5 Hz, 2H), 2.04 (m, 1H), 1.88 (qn, J=7 Hz,
2H), 1.68 (m, 1H), 1.47 (m, 1H), 1.32 (m, 1H), 1.29 (s, 3H), 1.25
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 209.5, 138.4, 128.3,
127.6, 127.5, 72.8, 71.0, 69.2, 65.8, 45.1, 39.8, 35.3, 31.4, 29.4,
26.9, 23.8, 23.1
6l: 1H NMR (500 MHz, CDCl3) δ 7.35 (m, 4H), 7.27 (m, 1H),
5.61 (s, 1H), 4.61 (s, 1H), 4.53 (ABq, J=11 Hz, 2H), 3.66 (dd, J=
12, 4.5 Hz, 1H), 3.23 (dd, J=21, 13 Hz, 1H), 2.43 (m, 1H), 2.20
(m, 2H), 2.00 (m, 2H), 1.88 (m, 1H), 1.71 (m, 2H), 1.50 (m, 2H),
1.20 (s, 3H), 1.18 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 147.8,
139.0, 128.3, 127.7, 127.3, 125.8, 84.5, 71.1, 70.3, 66.7, 35.9, 34.1,
33.8, 33.4, 30.5, 30.3, 26.3, 22.3; HRMS (ESI, m/z) [M þ Na]þ
calcd for C20H28O2Na 323.1987, found 323.1994.
J. Org. Chem. Vol. 76, No. 4, 2011 1095

Zheng et al.
JOCArticle
4m: 1H NMR (500 MHz, CDCl3) δ 4.00 (t, J=6 Hz, 2H), 3.60
(dd, J=11.5, 4 Hz, 1H), 3.26 (dd, J=12, 9.5 Hz, 1H), 2.43 (t, J=
7.5 Hz, 2H), 2.32 (m, 2H), 2.0 (m, 1H), 1.87 (qn, J=7 Hz, 2H),
1.67 (m, 1H), 1.44 (m, 2H), 1.28 (m, 1H), 1.14 (s, 3H), 1.29 (s, 9H),
1.12 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 208.3, 178.3, 71.0,
65.7, 63.3, 45.1, 39.3, 38.7, 35.2, 31.4, 29.2, 27.1, 25.9, 23.1, 22.7.
5m: 1H NMR (500 MHz, CDCl3) δ 5.45 (s, 1H), 4.46 (d, J=
5 Hz, 1H), 4.03 (t, J=6.5 Hz, 2H), 2.22 (m, 3H), 2.12 (m, 2H),
1.82 (m, 3H), 1.51 (m, 2H), 1.20 (m, 1H), 1.20 (s, 3H), 1.17 (s,
12H); 13C NMR (125 MHz, CDCl3) δ 178.5, 150.3, 125.0, 76.0,
64.0, 39.6, 38.7, 36.9, 33.6, 30.2, 27.8, 27.2, 26.5, 24.1, 22.5;
HRMS (ESI, m/z) [M þ H]þ calcd for C18H31O3 295.2273,
found 295.2272.
4s: 1H NMR (500 MHz, CDCl3) δ 2.71 (dd, J=8, 5 Hz, 1H),
2.58 (m, 2H), 2.41 (t, J=7.5 Hz, 2H), 1.90 (m, 1H), 1.63 (m, 1H),
1.57 (m, 2H), 1.31 (m, 3H), 1.27 (s, 3H), 1.25 (s, 3H), 0.89 (t, J=
7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 210.2, 63.4, 58.7,
42.6, 39.2, 25.9, 24.7, 22.9, 22.3, 18.7, 13.8.
1
6s: H NMR (500 MHz, CDCl3) δ 5.26 (s, 1H), 2.72 (t, J=
6 Hz, 2H), 2.26 (m, 4H), 2.21 (m, 1H), 1,71 (m, 2H), 1.35 (m,
1H), 1.29 (s, 3H), 1.25 (s, 3H), 0.98 (d, J=7.5 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 142.7, 130.3, 64.2, 58.3, 39.8, 34.8, 32.5,
27.9, 27.2, 24.8, 21.3, 18.7; HRMS (ESI, m/z) [M þ H]þ calcd for
C11H19O 167.1436, found 167.1441.
4t: 1H NMR (500 MHz, CDCl3) δ 4.19 (s, 2H), 4.18 (s, 2H),
3.58 (m, 1H), 3.23 (m, 1H), 1.86 (m, 2H), 1.68 (m, 2H), 1.48 (m,
1H), 1.29 (m, 4H), 1.21 (m, 1H), 1.14 (d, J = 6 Hz, 6H); 13C
NMR (125 MHz, CDCl3) δ 207.2, 78.5, 72.7, 72.2, 72.0, 31.8,
25.6, 23.9, 21.7.
4n: 1H NMR (500 MHz, CDCl3) δ 2.37 (t, J=7.5 Hz, 2H),
2.24 (d, J=7 Hz, 2H), 1.81 (m, 1H), 1.64 (m, 5H), 1.53 (qn J=
7 Hz, 2H), 1.31 (m, 4H), 1.13 (m, 1H), 0.88 (m, 5H); 13C NMR
(125 MHz, CDCl3) δ 211.2, 50.5, 43.2, 33.9, 33.2, 26.2, 26.0,
25.9, 22.3, 13.8.
5t: 1H NMR (500 MHz, CDCl3) δ 5.74 (s, 1H), 4.57 (s, 2H),
4.03 (s, 2H), 3.58 (m, 1H), 1.81 (m, 2H), 1.56 (m, 2H), 1.48 (m,
1H), 1.26 (m, 5H), 1.12 (d, J=6.5 Hz, 6H).
5n: 1H NMR (500 MHz, CDCl3) δ 5.21 (s, 1H), 2.70 (m, 1H),
2.36 (m, 2H), 2.11 (m, 1H), 1.96 (d, J=6.5 Hz, 2H), 1.70 (m, 4H),
1.46 (m, 6H), 0.99 (d, J=6.5 Hz, 3H), 0.85 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 142. 4, 131.0, 39.8, 39.2, 35.9, 34.7, 33.4,
32.6, 26.6, 26.4, 21.4; HRMS (EI, m/z) [M]þ calcd for C10H16
136.1252, found 136.1244.
6t: 1H NMR (500 MHz, CDCl3) δ 5.59 (s, 1H), 4.59 (s, 2H),
4.06 (s, 2H), 3.28 (m, 1H), 1.81 (m, 2H), 1.56 (m, 2H), 1.48 (m,
1H), 1.28 (s, 6H), 1.26 (m, 5H); 13C NMR for 5t and 6t (125
MHz, CDCl3) δ 137.7, 136.9, 130.6, 129.2, 74.1, 74.6, 72.2, 71.1,
70.2, 70.0, 63.8, 63.4, 37.0, 32.1, 27.6, 25.8, 24.0, 23.8, 23.4, 21.8;
HRMS (ESI, m/z) [M þ Na]þ calcd for C13H22O2Na 233.1517,
found 233.1514.
4o: 1H NMR (500 MHz, CDCl3) δ 4.41 (qn, J=6 Hz, 1H),
4.14 (m, 1H), 3.62 (dd, J=11.5, 4 Hz, 1 H), 3.51 (m, 1H), 3.28
(dd, J=11.5, 11 Hz), 2.85 (dt, J=16.5, 5.5 Hz, 1H), 2.53 (dd, J=
16.5, 6.5 Hz, 1H), 2.34 (m, 2H), 1.87 (m, 1H), 1.69 (m, 1H), 1.45
4u: 1H NMR (500 MHz, CDCl3) δ 4.20 (s, 2H), 4.15 (s, 2H),
3.90 (br s, 1H), 3.25 (m, 1H), 1.88 (m, 2H), 1.78-1.61 (8H), 1.50
(br s, 3H), 1.33-1.20 (5H); 13C NMR (125 MHz, CDCl3) δ
207.1, 82.5, 78.5, 72.8, 72.0, 32.0, 25.6, 23.9, 23.4.
(m, 2H), 1.35 (s, 3H), 1.30 (s, 3H), 1.16 (s, 3H), 1.14 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 207.2, 108.8, 71.6, 71.0, 69.3, 65.7,
47.3, 45.7, 35.2, 31.3, 29.3, 26.8, 25.8, 25.4, 23.3
5u and 6u: key resonances for 5u: 1H NMR (500 MHz,
CDCl3) δ 5.74 (s, 1H), 4.57 (s, 2H), 4.00 (s, 2H), 3.91 (m, 1H);
HRMS (ESI, m/z) [M þ H]þ calcd for C15H25O2 237.1855,
found 237.1856; 6u: 1H NMR (500 MHz, CDCl3) δ 5.60 (s, 1H),
4.55 (s, 2H), 4.08 (s, 2H), 3.26 (m, 1H), 1.88 (m, 2H), 1.78-1.61
(8H), 1.50 (br s, 3H), 1.33-1.20 (5H); 13C NMR (125 MHz,
CDCl3) δ 137.4, 128.6, 98.3, 77.2, 73.9, 63.5, 38.3, 32.1, 25.7,
24.4, 24.1.
6o: 1H NMR (500 MHz, CDCl3) δ 5.41 (s, 1H), 5.03 (d, J=6.4
Hz, 1H), 4.71 (t, J=5.5 Hz, 1H), 3.63 (m, 1H), 3.27 (m, 1H), 2.46
(m, 2H), 1.95 (m, 2H), 1.66 (m, 2H), 1.37 (s, 3H), 1.33 (m, 1H),
1.30 (s, 3H), 1.18 (s, 3H), 1.15 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 144.5, 125.5, 109.5, 85.3, 78.1, 71.1, 66.4, 41.0, 35.8,
34.0, 33.7, 30.2, 27.5, 26.4, 25.6, 22.4; HRMS (ESI, m/z) [M þ
H]þ calcd for C16H27O3 267.1960, found 267.1949.
4u0: 1H NMR (500 MHz, CDCl3) δ 4.23 (s, 2H), 4.14 (s, 2H),
3.90 (m, 1H), 3.17 (m, 1H), 2.06 (d, J=11.5 Hz, 2H), 1.78 (m,
2H), 1.70 (m, 6H), 1.15 (m, 2H), 1.21 (m, 2H), 0.97 (m, 3H), 0.79
(s, 9H); 13C NMR (125 MHz, CDCl3) δ 207.1 82.5, 79.6, 72.9,
72.1, 47.3, 32.3, 32.2, 32.0, 27.6, 25.5, 23.4.
4q: 1H NMR (500 MHz, CDCl3) δ 5.86 (m, 1H), 5.26 (d, J=
17.5 Hz, 1H), 5.18 (d, J=10.5 Hz, 1H), 3.99 (d, J=6 Hz, 2H),
3.96 (s, 2H), 3.62 (dd, J=11.5, 4.5 Hz, 1H), 3.27 (dd, J=11.5, 9.5
Hz, 1H), 2.31 (ABX, JAB=7 Hz, JAX=9 Hz, JBX=9.5 Hz, 2H),
2.04 (m, 1H), 1.69 (m, 1H), 1.47 (m, 2H), 1.36 (m, 1H), 1.14 (s,
3H), 1.11 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 207.5, 133.7,
117.9, 75.2, 72.3, 71.0, 65.7, 41.1, 35.2, 31.0, 29.3, 25.9, 23.1.
6q: 1H NMR (500 MHz, CDCl3) δ 5.79 (m, 1H), 5.39 (s, 1H),
5.24 (d, J=17.5 Hz, 1H), 5.16 (br s, 1H), 5.07 (d, J=10.5 Hz,
1H), 4.57 (m, 2H), 3.68 (dd, J=11.5, 4.5 Hz, 1H), 3.30 (dd, J=
11.5, 9.5 Hz, 1H), 1.99 (m, 2H), 1.72 (m, 2H), 1.54 (m, 1H), 1.45
(m, 1H), 1.31 (m, 1H), 1.20 (s, 3H), 1.17 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 138.5, 123.3, 111.5, 87.5, 76.7, 71.2, 66.3, 35.7,
34.1, 30.0, 29.9, 26.4, 22.5; LRMS (ESI, m/z) [M þ Na]þ calcd
for C14H22O2Na 245.1, found 245.1.
5u0 and 6u0: key resonances for 5u0: 1H NMR (500 MHz,
CDCl3) δ 5.97 (s, 1H), 4.57 (s, 2H), 4.01 (s, 2H), 3.94 (m, 1H);
key resonances for 6u0: 5.59 (s, 1H), 4.54 (s, 2H), 4.08 (s, 2H),
13
3.16 (m, 2H); C NMR (125 MHz, CDCl3) for 5u0 and 6u0 δ
137.6, 137.4, 128.6, 127.1, 98.3, 90.9, 81.2, 78.4, 73.9, 73.5, 64.6,
63.6, 47.4, 38.38, 38.35, 32.6, 32.29, 32.26, 27.63, 25.62, 25.51,
24.41, 23.57; HRMS (ESI, m/z) [M þ H]þ calcd for C19H33O2
293.2481, found 293.2479.
4v: 1H NMR (500 MHz, CDCl3) δ 4.26 (s, 2H), 4.22 (s, 2H),
3.27 (m, 1H), 3.18 (m,1H), 2.07 (d, J=12 Hz, 2H), 1.89 (m, 2H),
1,79 (m, 4H), 1.52 (m, 1H), 1.34-1.17 (m, 7H), 1.09 (m, 2H),
0.83 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 207.4, 79.6, 78.6,
72.1, 47.3, 32.3, 32.2, 31.8, 27.6, 25.6, 25.5, 23.9.
4r: 1H NMR (500 MHz, CDCl3) δ 3.61 (m, 1H), 3.27 (m, 1H),
2.35 (m, 2H), 2.26 (m, 2H), 2.01 (m, 1H), 1.66 (m, 1H), 1.51 (m,
2H), 1.48 (m, 2H), 1.29 (m, 3H), 1.15 (s, 3H), 1.13 (s, 3H), 0.87
(m, 3H); 13C NMR (125 MHz, CDCl3) δ 210.0, 71.0, 65.8, 45.0,
42.9, 35.3, 31.4, 29.3, 25.9, 25.8, 23.0, 22.2, 13.8.
5v and 6v: key resonances for 5v: 1H NMR (500 MHz, CDCl3)
δ 5.98 (s, 1H), 4.58 (s, 2H), 4.08 (s, 2H), 3.25 (m, 1H); key
resonances for 6v: 1H NMR (500 MHz, CDCl3) δ 5.73 (s, 1H),
4.57 (s, 2H), 4.08 (s, 2H), 3.17 (m, 1H); 13C NMR (125 MHz,
CDCl3) for 5v and 6v δ 137.8, 137.4, 129.2, 127.0, 90.9, 89.8,
78.3, 73.7, 73.5, 63.78, 63.74, 47.43, 47.40, 38.3, 37.0, 32.6, 32.2,
32.1, 27.66, 27.63, 25.77, 25.62, 25.51, 25.45, 24.12, 23.46;
HRMS (ESI, m/z) [M þ H]þ calcd for C20H35O2 307.2637,
found 307.2635.
5r and 6r: key resonances for 5r: 1H NMR (500 MHz, CDCl3)
δ 5.43 (s, 1H), 4.47 (d, J=6 Hz, 1H), 1.21 (s, 3H), 1.19 (s, 3H),
0.88 (t, J=7.2 Hz, 3H); key resonances for 6r: H NMR (500
1
MHz, CDCl3) δ 5.23 (s, 1H), 3.63 (m, 1H), 3.26 (dd, J=11.5, 10
Hz, 1H), 2.68 (m, 1H), 1.177 (s, 3H), 1.170 (s, 3H), 0.97 (dd, J=
6.8, 3 Hz, 3H); 13C NMR for 5r and 6r (125 MHz, CDCl3) δ
151.7, 141.1, 131.6, 124.3, 76.1, 71.1, 70.6, 66.8, 39.8, 39.6, 37.0,
36.0, 34.6, 34.5, 34.1, 33.9, 33.7, 32.5, 31.2, 30.4, 30.2, 29.5, 26.5,
24.2, 22.6, 22.2, 21.2, 13.9; HRMS (ESI, m/z) [M þ H]þ calcd for
C14H25O 209.1905, found 209.1912.
4w: 1H NMR (500 MHz, CDCl3) δ 4.32 (s, 2H), 4.12 (s, 2H),
3.53 (br s, 1H), 3.19 (m, 1H), 2.07 (d, J=12 Hz, 2H), 1.97 (d, J=
12 Hz, 2H), 1.79 (m, 2H), 1.50 (m, 2H), 1.48-1.20 (m, 6H), 1.00
1096 J. Org. Chem. Vol. 76, No. 4, 2011

Zheng et al.
JOCArticle
(m, 4H), 0.83 (s, 9H), 0.82 (s, 9H); 13C NMR (125 MHz, CDCl3)
δ 207.5, 79.5, 74.3, 72.1, 71.9, 47.8, 47.3, 32.5, 32.3, 32.2, 30.2,
27.6, 27.4, 25.5, 21.3.
(m, 2H), 1.70 (d, J=10.5 Hz, 1H), 1.68-1.62 (m, 1H), 1.58 (dd, J
=3.0, 11.5 Hz, 1H), 1.27 (s, 3H), 1.21 (dd, J=3.5, 10.5 Hz, 1H);
13C NMR (125 MHz, CDCl3) δ 208.1, 86.5, 80.1, 45.8, 43.9,
42.8, 42.0, 41.9, 41.0, 36.4, 30.6, 23.2; HRMS (EI, m/z) [M]þ
calcd for C12H18O2 194.1307, found 194.1308.
13c: colorless liquid, volatile; Rf 0.75 (hexanes/ethyl acetate=
5/1); 1H NMR (500 MHz, CDCl3) δ 5.33 (s, 1H), 4.39 (d, J=4.5
Hz, 1H), 2.30 (t, J = 16.5 Hz, 1H), 2.25 (t, J = 6.5 Hz, 1H),
1.98-1.90 (m, 2H), 1.86-1.76 (m, 2H), 1.72 (s, 3H), 1.69 (d, J=
11.0 Hz, 2H), 1.44 (dd, J=3.5, 10.5 Hz, 1H), 1.37 (d, J=11.0 Hz,
1H), 1.34 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 141.8, 129.2,
83.6, 77.3, 56.2, 50.2, 48.2, 45.9, 43.8, 42.5, 36.3, 23.1, 17.6;
HRMS (EI, m/z) [M]þ calcd for C13H18O 190.1358, found
190.1357.
14c: 1:1 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.77 (hexanes/ethyl acetate=5/1); 1H NMR (500 MHz,
CDCl3) δ 4.82 (m, 1H), 4.08 (br s, 1H), 2.23-2.15 (m, 3H),
2.08-1.95 (m, 3H), 1.78-1.66 (m, 2H), 1.63 (d, J=3.5 Hz, 3H),
1.62-1.53 (m, 2H), 1.35 (d, J=3.5 Hz, 3H), 1.27-1.22 (m, 1H),
0.06 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 209.0, 208.9, 90.3,
86.4, 82.3, 80.5, 80.2, 44.3, 42.8, 42.7, 42.2, 42.1, 41.1, 40.8, 40.0,
39.7, 35.2, 23.4, 18.7, 18.6, -0.7; HRMS (EI, m/z) [M]þ calcd for
C17H28OSi 276.1909, found 276.1908.
25a: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 7.32-7.28 (m, 2H),
7.24-7.18 (m, 3H), 4.91 (q, J = 4.0 Hz, 1H), 2.73 (t, J = 7.0
Hz, 2H), 2.24 (qn, J=4.0 Hz, 2H), 1.71 (d, J=3.5 Hz, 3H), 0.09
(s, 9H); 13C NMR (125 MHz, CDCl3) δ 208.7, 142.4, 128.4,
128.3, 125.8, 91.7, 83.0, 35.0, 34.4, 18.3, -0.7; HRMS (EI, m/z)
[M]þ calcd for C15H22Si 230.1491, found 230.1488.
5w and 6w: key resonances for 5w: 1H NMR (500 MHz,
CDCl3) δ 5.99 (s, 1H), 4.61 (s, 2H), 4.05 (s, 2H), 3.55 (br s, 1H),
0.86 (s, 9H), 0.84 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 138.1,
126.8, 90.7, 73.5, 72.4, 63.4, 47.8, 47.3, 38.3, 32.6, 32.3, 30.4,
27.6, 27.4, 25.6, 21.3; key resonances for 6w: 1H NMR (500
MHz, CDCl3) δ 5.50 (s, 1H), 4.60 (s, 2H), 4.08 (s, 2H), 3.19 (m,
1H), 0.89 (s, 9H), 0.83 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
137.1, 130.8, 88.7, 78.2, 73.9, 63.7, 47.4, 36.5, 32.6, 32.4, 30.4,
27.6, 27.4, 25.6, 25.5, 23.3; HRMS (ESI, m/z) [M þ H]þ calcd for
C24H43O2 363.3263, found 363.3264.
4x: 1H NMR (500 MHz, CDCl3) δ 5.09 (t, J=6 Hz, 1H), 4.23
(s, 2H), 4.21 (s, 2H), 3.52 (m, 2H), 3.19 (m, 1H), 2.08 (d, J=12
Hz, 2H), 1.97 (m, 2H), 1.79 (m, 2H), 1.66 (s, 3H), 1.64 (m, 1H),
1.59 (s, 3H), 1.56 (m, 1H), 1.42 (m, 2H), 1.24 (m, 4H), 0.99 (m,
2H), 0.89 (d, J=7 Hz, 3H), 0.83 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 207.0, 131.2, 124.7, 79.7, 74.7, 72.1, 70.3, 47.3, 37.1,
36.4, 32.3, 32.2, 29.5, 27.6, 25.7, 25.5, 25.4, 19.5, 17.6.
5x and 6x: key resonances for 5x: 1H NMR (500 MHz,
CDCl3) δ 6.00 (s, 1H), 5.09 (t, J = 7 Hz, 1H), 4.59 (s, 2H),
4.01 (s, 2H), 3.46 (m, 2H); key resonances for 6x: 1H NMR (500
MHz, CDCl3) δ 5.67 (d, J=1.5 Hz, 1H), 5.09 (t, J=7 Hz, 1H),
4.89 (br s, 1H), 4.62 (m, 2H), 4.10 (s, 2H), 3.16 (m, 1H); 13C
NMR (125 MHz, CDCl3) for 5x and 6x: δ 138.3, 138.2, 137.2,
131.0, 127.6, 126.2, 125.9, 124.8, 124.7, 90.9, 85.0, 84.6, 78.2,
74.8, 73.4, 69.0, 66.6, 63.5, 47.4, 47.3, 43.3, 38.3, 37.7, 37.3,
36.63, 33.60, 32.6, 32.2, 30.3, 29.8, 29.6, 29.5, 27.6, 25.7, 25.6,
25.5, 25.46, 25.42, 20.1, 19.5, 19.4, 17.3; HRMS (ESI, m/z) [M þ
H]þ calcd for C24H43O2 363.3263, found 363.3265.
25b: colorless liquid, volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 7.31-7.26 (m, 2H),
7.23-7.16 (m, 3H), 5.01 (m, 1H), 2.73 (m, 2H), 2.24 (m, 2H),
1.97 (m, 2H), 1.02 (t, J=7.5 Hz, 3H), 0.09 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 207.9, 142.6, 128.4, 128.3, 125.7, 98.5, 85.0,
34.5, 33.7, 24.9, 12.5, -0.7; HRMS (EI, m/z) [M]þ calcd for
C16H24Si 244.1647, found 244.1647.
4y: 1H NMR (500 MHz, CDCl3) δ 4.37 (m, 2H), 4.15 (m, 2H),
3.52 (br s, 1H), 3.09 (m, 1H), 2.22 (m, 1H), 2.01 (m, 3H), 1.62 (m,
2H), 1.48 (br s, 2H), 1.32 (m, 6H), 0.98 (m, 1H), 0.85 (m, 6H),
0.83 (s, 9H), 0.76 (m, 3H); 13C NMR (125 MHz, CDCl3) δ 207.3,
80.3, 74.2, 72.5, 72.0, 48.0, 47.7, 39.9, 34.4, 32.5, 31.4, 30.2, 27.4,
25.6, 23.3, 22.2, 21.3, 20.9, 16.2.
5y and 6y: key resonances for 5y: 1H NMR (500 MHz,
CDCl3) δ 5.85 (s, 1H), 4.63 (m, 2H), 4.04 (s, 2H), 3.54 (br s,
1H); 6y: 1H NMR (500 MHz, CDCl3) δ 5.48 (s, 1H), 4.62 (ABq,
J=12 Hz, 2H), 4.21 (ABq, J=12.5 Hz, 2H), 3.07 (m, 1H), 2.17
(m, 1H), 2.08 (m, 1H), 1.75 (m, 2H), 1.64 (m, 4H), 1.42-1.24 (m,
7H), 0.96 (m, 3H), 0.91 (d, J=9.5 Hz, 3H), 0.88 (d, J=7 Hz, 3H),
0.84 (s, 9H), 0.75 (d, J=7 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 137. 0, 130.9, 88.6, 79.4, 74.1, 64.2, 48.2, 47.3, 40.3, 36.5, 36.4,
34.5, 32.4, 31.5, 27.6, 25.6, 23.3, 22.3, 20.9, 16.2; HRMS (ESI,
m/z) [M þ H]þ calcd for C24H43O2 363.3263, found 363.3274.
25c: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 7.32-7.28 (m, 2H),
7.23-7.18 (m, 3H), 4.98 (m, 1H), 2.72 (m, 2H), 2.23 (m, 2H),
1.96 (qn, J=4.0 Hz, 2H), 1.46 (m, 2H), 0.95 (t, J=7.5 Hz, 3H),
0.11 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 208.3, 142.6, 128.4,
128.3, 125.6, 96.5, 84.3, 34.5, 34.2, 33.7, 21.1, 14.1, -0.7; HRMS
(EI, m/z) [M]þ calcd for C17H26Si 258.1804, found 258.1804.
25d: colorless liquid, volatile; Rf 0.78 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 7.32-7.28 (m, 4H),
7.23-7.18 (m, 6H), 5.03 (m, 1H), 2.73 (m, 4H), 2.27 (m, 4H),
0.10 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 208.1, 142.4, 128.4,
128.3, 125.8, 96.7, 85.1, 34.4, 33.8, -0.7; HRMS (EI, m/z) [M]þ
calcd for C22H28Si 320.1960, found 320.1962.
1
4z: H NMR (500 MHz, CDCl3) δ 4.30 (ABq, J=17.5 Hz,
2H), 4.26 (s, 2H), 3.17 (m, 1H), 3.09 (m, 1H), 2.20 (m, 1H), 2.06
(m, 3H), 1.78 (m, 2H), 1.63 (m, 2H), 1.43 (m, 1H), 1.32 (m, 5H),
0.99 (m, 4H), 0.86 (m, 6H), 0.79 (s, 9H), 0.75 (d, J=7.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 207.1, 80.4, 79.5, 72.6, 72.0,
48.0, 47.3, 41.3, 39.9, 34.4, 32.3, 32.2, 31.4, 27.6, 27.4, 25.6, 25.5,
23.2, 22.2, 20.9, 16.2.
25e and 25e0: inseparable mixture; colorless liquid; volatile; Rf
0.98 (hexanes/ethyl acetate = 10/1); 1H NMR (500 MHz,
CDCl3) δ 7.33-7.29 (m, 2.5H), 7.26-7.17 (m, 3.8H), 5.32 (d,
J = 1.5 Hz, 1H), 5.00 (m, 0.24H), 2.80 (t, J = 7.5 Hz, 2H),
2.76-2.72 (m, 1.5H), 2.39 (t, J=7.5 Hz, 2H), 2.34-2.24 (m, 2H),
2.14 (m, 1H), 2.00 (m, 0.5H), 1.41 (m, 2.5H), 1.03 (d, J=7.0 Hz,
3H), 0.95 (t, J=7.5 Hz, 0.75H), 0.12 (s, 2.3H); 13C NMR (125
MHz, CDCl3), characteristic peaks for allene 25e: δ 208.2, 142.6,
128.39, 128.30, 125.7, 96.7, 84.3, 34.5, 33.7, 31.7, 30.1, 22.6, 14.1,
-0.7; 13C NMR (125 MHz, CDCl3), characteristic peaks for
alkene 25e0: δ 143.3, 142.5, 130.2, 128.35, 128.27, 125.7, 39.9,
35.0, 34.4, 33.2, 32.6, 21.3; 25e: HRMS (EI, m/z) [M]þ calcd for
C18H28Si 272.1960, found 272.1964; 25e0: HRMS (EI, m/z) [M]þ
calcd for C14H18 186.1409, found 186.1410.
5z and 6z: key resonances for 5z: 1H NMR (500 MHz, CDCl3)
δ 5.84 (s, 1H), 4.62 (ABq, J=12 Hz, 2H), 4.10 (s, 2H), 3.14 (m,
1H); key resonances for 6z: 1H NMR (500 MHz, CDCl3) δ 5.98
(s, 1H), 4.62 (ABq, J=12 Hz, 2H), 4.22 (ABq, J=12.5 Hz, 2H),
3.08 (m, 1H); 13C NMR (125 MHz, CDCl3) for 5z and 6z δ
137.7, 127.2, 126.4, 94.3, 90.9, 79.4, 77.8, 74.3, 73.6, 64.4, 63.7,
52.1, 49.5, 48.2, 47.3, 40.3, 38.3, 38.2, 35.0, 34.5, 32.7, 32.4, 32.2,
31.5, 31.3, 27.65, 27.62, 25.8, 25.6, 25.58, 25.50, 24.4, 23.6, 23.4,
22.3, 20.9, 18.7, 16.2; HRMS (ESI, m/z) [M þ H]þ calcd for
C24H43O2 363.3263, found 363.3260.
11c: colorless liquid; Rf 0.2 (hexanes/ethyl acetate=5/1); 1H
NMR (500 MHz, CDCl3) δ 3.92 (d, J=5.0 Hz, 1H), 2.74 (dd, J=
8.0, 17.5 Hz, 1H), 2.40 (dd, J=5.5, 18.0 Hz, 1H), 2.12 (t, J=6.5
Hz, 1H), 2.06 (s, 3H), 2.02 (s, 1H), 1.98-1.94 (m, 1H), 1.91-1.86
24f: colorless liquid; Rf 0.40 (hexanes/ethyl acetate=10/1); 1H
NMR (500 MHz, CDCl3) δ 2.14 (s, 2H), 2.08 (s, 3H), 1.91 (m,
3H), 1.67-1.56 (m, 12H); 13C NMR (125 MHz, CDCl3) δ 208.9,
57.0, 42.5, 36.7, 33.4, 33.1, 28.6.
J. Org. Chem. Vol. 76, No. 4, 2011 1097

Zheng et al.
JOCArticle
25f: colorless liquid, volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ4.75 (m, 1H), 1.95 (br s, 3H),
1.73-1.54 (m, 17H), 0.09 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
210.9, 87.7, 80.4, 48.4, 42.7, 37.2, 34.4, 28.8, 21.4, -0.7; HRMS
(EI, m/z) [M]þ calcd for C18H30Si 274.2117, found 274.2115.
25f0: colorless liquid, volatile; Rf 0.98 (hexanes/ethyl acetate=
16.9, -0.4, -0.9; HRMS (CI, m/z) [M]þ calcd for C16H28O2Si
280.1858, found 280.1853.
26d: colorless liquid; Rf 0.23 (hexanes/ethyl acetate=5/1); 1H
NMR (500 MHz, CDCl3) δ 4.30 (m, 1H), 3.31 (s, 3H), 3.30 (s,
3H), 2.35-2.30 (m, 2H), 2.13 (s, 3H), 1.53-1.42 (m, 2H), 1.06 (s,
3H), 0.88 (s, 3H), 0.88-0.81 (m, 1H), 0.64-0.60 (m, 1H); 13C
NMR (125 MHz, CDCl3) δ 208.9, 105.1, 53.3, 39.5, 29.7, 28.7,
28.3, 21.4, 21.1, 16.8, 15.2;
1
10/1); H NMR (500 MHz, CDCl3) δ 5.36 (s, 1H), 2.49 (br s,
1H), 2.05 (br s, 1H), 2.00-1.91 (m, 3H), 1.91-1.81 (m, 2H),
1.78-1.54 (m, 12H); 13C NMR (125 MHz, CDCl3) δ 139.9,
128.0, 57.1, 50.0, 42.5, 39.0, 38.4, 38.1, 32.2, 30.3, 29.8, 28.8,
28.2, 17.8; HRMS (EI, m/z) [M]þ calcd for C14H20 188.1565,
found 188.1562.
27d: 1:1 mixture of two diastereomers; colorless liquid; Rf 0.75
(hexanes/ethyl acetate = 5/1); H NMR (500 MHz, CDCl3) δ
1
4.85 (m, 1H), 4.36 (m, 1H), 3.33 (s, 6H), 1.97 (dt, J=15.5, 5.0 Hz,
0.5H), 1.90-1.80 (m, 1H), 1.77-1.71 (m, 0.5H), 1.65 (d, J=4.0
Hz, 3H), 1.57-1.47 (m, 1.5H), 1.32-1.26 (m, 0.5H), 1.04 (s,
1.5H), 1.02 (s, 1.5H), 0.93 (s, 1.5H), 0.89 (s, 1.5H), 0.62-0.51 (m,
2H), 0.07 (s, 4.5H), 0.06 (s, 4.5H); 13C NMR (125 MHz, CDCl3)
δ 209.3, 209.0, 105.2, 92.1, 82.4, 53.2, 53.0, 52.9, 52.8, 29.3, 29.2,
29.1, 28.5, 28.2, 28.1, 25.1, 24.8, 21.6, 21.5, 18.5, 18.4, 17.0, 16.9,
15.2, 14.9, -0.7, -0.8; HRMS (CI, m/z) [M - H]þ calcd for
C17H31O2Si 295.2093, found 295.2090.
1
25g0: H NMR (500 MHz, CDCl3) δ 4.32 (s, 1H), 2.24 (m,
1H), 1.95 (m, 4H), 1.85 (m, 4H), 1.82 (m, 4H), 1.72 (s, 3H), 1.69
(m, 5H), 1.44 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 139.8,
135.9, 53.2, 44.7, 42.2, 39.7, 38.5, 37.7, 37.6, 31.6, 30.3, 29.7,
29.4, 27.7, 17.5; HRMS (EI, m/z) [M]þ calcd for C14H20
188.1565, found 188.1558.
1
25h: H NMR (500 MHz, CDCl3) δ 4.79 (m, 1H), 1.82 (m,
2H), 1.79 (m, 4H), 1.62 (d, J=3.5 Hz, 3H), 1.39 (m, 1H), 1.36 (m,
4H), 0.91 (m, 2H), 0.08 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
209.3, 90.0, 81.2, 41.3, 35.9, 33.4, 26.6, 18.2, -0.6; HRMS (EI,
m/z) [M]þ calcd for C14H26Si 222.1803, found 222.1796.
26a: colorless liquid; Rf 0.24 (hexanes/ethyl acetate=10/1);
1H NMR (500 MHz, CDCl3) δ 7.30 (t, J=7.5 Hz, 2H), 7.22 (t,
J=7.5 Hz, 1H), 7.10 (d, J=7.5 Hz, 2H), 2.54 (ddd, J=4.0, 7.0,
10.0 Hz, 1H), 2.31 (s, 3H), 2.23 (ddd, J=4.0, 5.0, 8.5 Hz, 1H),
1.69 (ddd, J=4.5, 5.0, 9.0 Hz, 1H), 1.39 (ddd, J=4.5, 7.0, 8.0 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 206.8, 140.4, 128.6, 126.6,
126.1, 32.9, 30.9, 29.0, 19.2.
27a: 1:1 mixture of two diastereomers; colorless liquid; vola-
tile; Rf 0.81 (hexanes/ethyl acetate=10/1); 1H NMR (500 MHz,
CDCl3) δ 7.30-7.25 (m, 2H), 7.18-7.15 (m, 1H), 7.15-7.08 (m,
2H), 5.00 (m, 1H), 1.89 (ddd, J=4.5, 5.0, 9.5 Hz, 0.5H), 1.84
(ddd, J=5.0, 5.1, 9.0 Hz, 0.5H), 1.77 (t, J=4.0 Hz, 3H), 1.39 (m,
1H), 1.14-1.03 (m, 2H), 0.11 (d, J=1.5 Hz, 9H); 13C NMR (125
MHz, CDCl3) δ 208.1, 208.0, 143.1, 128.3, 125.9, 125.8, 125.5,
94.2, 94.1, 84.6, 25.4, 25.3, 25.1, 24.8, 17.8, 17.7, 16.3, 15.8, -0.7,
-0.8; HRMS (CI, m/z) [M]þ calcd for C16H22Si 242.1491, found
242.1492.
26e: colorless liquid; Rf 0.45 (hexanes/ethyl acetate=5/1); 1H
NMR (500 MHz, CDCl3) δ 3.71-3.60 (m, 5H), 2.43-2.31 (m,
4H), 1.99-1.87 (m, 2H), 1.76-1.65 (m, 2H), 1.14 (s, 3H),
1.06-0.97 (m, 24H); 13C NMR (125 MHz, CDCl3) δ 210.7,
177.0, 59.9, 51.7, 43.7, 41.6, 37.6, 35.9, 33.1, 21.4, 18.0, 11.9, 7.8;
HRMS (EI, m/z) [M - C3H7]þ calcd for C17H33O4Si 329.2148,
found 329.2156.
27e: 1:1 mixture of two diastereomers; colorless liquid; Rf 0.77
1
(hexanes/ethyl acetate = 5/1); H NMR (500 MHz, CDCl3) δ
4.95 (m, 1H), 3.72-3.62 (m, 5H), 2.02-1.95 (m, 1H), 1.93-1.82
(m, 3H), 1.78-1.68 (m, 3H), 1.56-1.49 (m, 1H), 1.18 (s, 3H),
1.09-1.01 (m, 21H), 0.97 (t, J=7.5 Hz, 3H), 0.06 (s, 9H); 13
C
NMR (125 MHz, CDCl3) δ 207.7, 177.4, 98.5, 84.9, 84.8, 60.0,
51.5, 44.2, 41.8, 41.6, 38.1, 38.0, 26.6, 24.8, 21.5, 21.4, 18.0, 12.4,
12.0, -0.8; HRMS (EI, m/z) [M - C3H7]þ calcd for
C22H43O3Si2 411.2751, found 411.2751.
26f: colorless liquid; Rf 0.18 (hexanes/ethyl acetate=5/1); 1H
NMR (500 MHz, CDCl3) δ 2.63 (t, J=4.5 Hz, 1H), 2.52 (t, J=
6.0 Hz, 2H), 2.08 (s, 3H), 1.81 (m, 1H), 1.54 (m, 1H), 1.19 (s, 3H),
1.16 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 207.6, 63.2, 58.7,
40.1, 29.9, 24.7, 22.9, 18.6;
26b: colorless liquid; Rf=0.23 (hexanes/ethyl acetate=5/1);
1H NMR (500 MHz, CDCl3) δ 7.11 (d, J=8.5 Hz, 2H), 6.82 (d,
J=8.5 Hz, 2H), 3.77 (s, 3H), 2.86 (m, 4H), 1.90 (tt, J=3.5, 8.0
Hz, 1H), 1.01 (ddt, J=4.0, 7.5, 11.5 Hz, 2H), 0.85 (ddt, J=3.5,
7.0, 11.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 210.2, 157.9,
133.3, 129.3, 113.9, 55.3, 45.3, 29.1, 20.6, 10.7.
27b: colorless liquid; Rf=0.75 (hexanes/ethyl acetate=5/1);
1H NMR (500 MHz, CDCl3) δ 7.13 (d, J=8.0 Hz, 2H), 6.83 (d,
J=8.5 Hz, 2H), 5.00 (m, 1H), 3.78 (s, 3H), 2.70 (t, J=7.0 Hz,
2H), 2.30 (dt, J = 4.0, 9.5 Hz, 2H), 1.09 (m, 1H), 0.63 (m,
2H), 0.37 (ddt, J = 3.5, 8.5, 12.0 Hz, 1H), 0.29 (ddt, J = 3.5,
8.5, 12.5 Hz, 1H), 0.04 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
207.8, 157.8, 134.7, 129.2, 113.7, 85.8, 55.3, 34.2, 33.7, 11.8, 6.9,
5.5, -0.8; HRMS (EI, m/z) [M]þ calcd for C18H26OSi 286.1753,
found 286.1753.
26c: colorless liquid; Rf 0.20 (hexanes/ethyl acetate =10/1);
1H NMR (500 MHz, CDCl3) δ 3.56 (s, 3H), 2.80 (dd, J=7.5,
10.0 Hz, 1H), 2.30-2.16 (m, 3H), 1.98 (s, 3H), 1.88-1.79 (m,
2H), 1.24 (s, 3H), 0.77 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
207.4, 173.1, 54.1, 51.4, 43.2, 37.9, 34.8, 30.1, 22.9, 17.2.
27c: 1:1 mixture of two diastereomers; colorless liquid; Rf 0.50
(hexanes/ethyl acetate=10/1); 1H NMR (500 MHz, CDCl3) δ
4.94-4.87 (m, 1H), 3.64 (s, 3H), 2.32-2.17 (m, 4H), 2.02-1.92
(m, 1H), 1.57 (s, 1.5H), 1.56 (s, 1.5H), 1.44-1.37 (m, 1H), 1.13 (s,
1.5H), 1.12 (s, 1.5H), 0.88 (s, 1.5H), 0.82 (s, 1.5H), 0.12 (s, 4.5H),
0.02 (s, 4.5H); 13C NMR (125 MHz, CDCl3) δ 209.4, 209.2,
173.8, 173.7, 92.9, 92.5, 83.4, 83.3, 51.4, 45.4, 45.3, 42.3, 42.1,
38.3, 38.2, 35.2, 35.1, 30.53, 30.48, 27.4, 27.1, 18.2, 18.0, 17.2,
27f: 1:1 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.73 (hexanes/ethyl acetate=5/1); 1H NMR (500 MHz,
CDCl3) δ 4.86 (m, 1H), 2.76 (t, J=6.5 Hz, 1H), 2.09-1.97 (m,
2H), 1.67-1.57 (m, 5H), 1.31 (s, 3H), 1.27 (s, 3H), 0.06 (s, 9H);
13C NMR (125 MHz, CDCl3) δ 208.4, 91.3, 91.2, 83.1, 83.0,
64.0, 58.4, 29.8, 27.4, 27.3, 24.9, 18.7, 18.3, -0.8; HRMS (EI, m/
z) [M - CH3]þ calcd for C12H21OSi 209.1362, found 209.1364.
26g: colorless liquid; Rf 0.15 (hexanes/ethyl acetate=10/1);
1H NMR (500 MHz, CDCl3) δ 3.59 (dd, J=2.5, 10.0 Hz, 1H),
2.75-2.67 (m, 1H), 2.55-2.47 (m, 1H), 2.14 (s, 3H), 1.74-1.62
(m, 2H), 1.37 (s, 3H), 1.28 (s, 3H), 1.23 (s, 3H), 1.07 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 208.2, 106.7, 82.6, 80.2, 41.0, 30.0,
28.5, 26.9, 25.9, 23.2, 22.9;
27g: 1:1 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.51 (hexanes/ethyl acetate=10/1); 1H NMR (500 MHz,
CDCl3) δ 4.88 (m, 1H), 3.73 (dd, J=2.5, 10.0 Hz, 1H), 2.13 (m,
1H), 1.95 (m, 1H), 1.67(m, 3H), 1.62 (m, 1H), 1.47 (m, 1H), 1.42
(m, 3H), 1.34 (s, 3H), 1.25 (s, 1.5H), 1.24 (s, 1.5H), 1.09 (s, 1.5H),
1.08 (s, 1.5H), 0.08 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
208.5, 106.5, 91.7, 91.6, 83.4, 83.0, 80.2, 30.3, 29.9, 29.7, 28.6,
27.8, 27.6, 27.0, 26.9, 26.1, 22.9, 22.7, 18.5, 18.3, -0.8; HRMS
(CI, m/z) [M]þ calcd for C16H30O2Si 282.2015, found 282.2010.
27g0: colorless liquid; Rf 0.49 (hexanes/ethyl acetate=10/1);
1H NMR (500 MHz, CDCl3) δ 5.44 (s, 1H), 2.40 (m, 1H), 2.13
(m, 2H), 1.98 (m, 1H), 1.78 (s, 3H), 1.40 (s, 6H), 1.25 (s, 3H), 1.18
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 145.8, 126.3, 106.2, 97.9,
82.0, 35.0, 33.6, 29.7, 29.2, 24.7, 24.5, 17.2; HRMS (CI, m/z)
[M þ H]þ calcd for C12H21O2 197.1541, found 197.1539.
1098 J. Org. Chem. Vol. 76, No. 4, 2011

Zheng et al.
JOCArticle
26h: 1H NMR (500 MHz, CDCl3) δ 3.93 (ddd, J=12, 4, 1.5
Hz, 2H), 3.51 (ddd, J=11.5, 5.5, 2 Hz, 2H), 2.55 (dd, J=7, 1.5
2.38-2.03 (m, 4H), 1.92-1.49 (m, 6H); 13C NMR (125 MHz,
CDCl3) δ 208.8, 111.7, 95.6, 64.2, 39.0, 37.7, 31.5, 25.7, 21.3,
-0.6; HRMS (EI, m/z) [M - H]þ calcd for C14H23O2Si
251.1467, found 251.1480.
Hz, 2H), 2.11 (m, 1H), 2.09 (s, 3H), 1.35 (s, 3H), 1.32 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 207.0, 97.9, 63.8, 43.0, 30.2, 29.7,
24.5, 23.1.
29g: colorless liquid; Rf 0.98 (hexanes/ethyl acetate=10/1);
1H NMR (500 MHz, CDCl3) δ 4.88 (m, 1H), 4.37 (m, 1H), 2.30
(m, 1H), 2.04 (m, 1H), 1.82-1.33 (m, 8H), 0.88 (s, 9H), 0.0.09 (s,
9H), 0.03 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 208.7, 100.7,
83.0, 72.7, 38.9, 28.3, 27.8, 25.9, 23.7, 18.2, -0.5, -4.6, -4.9;
HRMS (ESI, m/z) [M - H]þ calcd for C18H35OSi2 323.2226,
found 323.2216.
29i: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 4.79 (m, 1H), 2.14 (m, 4H),
1.64-1.52 (m, 10H), 0.09 (s, 9H); 13C NMR (125 MHz, CDCl3)
δ 209.8, 96.1, 80.9, 31.2, 27.1, 26.7, 26.2, -0.4.
27h: 1H NMR (500 MHz, CDCl3) δ 4.84 (m, 1H), 3.88 (ddd,
J=22, 11, 5 Hz, 2H), 3.51 (ddd, J=20.5, 11, 5 Hz, 2H), 1.96 (m,
1H), 1.83 (m, 2H), 1.63 (d, J=3.5 Hz, 3H), 1.41(s, 3H), 1.40 (s,
3H), 0.07 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 208.4, 97.9,
88.6, 64.9, 32.8, 32.5, 26.7, 21.1, 18.2, -0.8; HRMS (ESI, m/z)
[M þ H]þ calcd for C10H27O2Si 255.1780, found 255.1786.
29a: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 4.89 (m, 1H), 2.36 (m, 4H),
1.65 (m, 4H), 0.07 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 205.0,
95.8, 83.6, 30.7, 27.4, 0.7; HRMS (EI, m/z) [M - H]þ calcd for
C10H17Si 165.1099, found 165.1112.
29j: 5:3 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.79 (hexanes/ethyl acetate=10/1); 1H NMR (500 MHz,
CDCl3) δ 4.83 (m, 1H), 2.91 (m, 2H), 2.36-2.05 (m, 4H), 2.01
(m, 1H), 1.76 (m, 1H), 1.72-1.46 (m, 2H), 0.1.45-1.18 (m, 2H),
0.08 (s, 5.4H), 0.06 (s, 3.6H); 13C NMR (125 MHz, CDCl3) δ
209.4, 209.3, 95.3, 95.1, 82.2, 82.1, 56.3, 56.0, 55.9, 55.8, 30.6,
30.5, 30.3, 27.4, 26.5, 26.2, 26.1, 26.0, -0.5, -0.6; HRMS (EI, m/
z) [M - H]þ calcd for C13H21OSi 221.1361, found 221.1376.
29k: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 4.88 (m, 1H), 1.98 (m, 4H),
1.48-1.36 (m, 18H), 0.09 (s, 9H); 13C NMR (125 MHz, CDCl3)
δ 209.5, 93.8, 82.5, 28.9, 24.6, 24.3, 24.2, 23.5, 22.6, -0.5; HRMS
(EI, m/z) [M]þ calcd for C17H32Si 264.2273, found 264.2276.
29l and 29l0: inseparable mixture; colorless liquid, volatile; Rf
0.98 (hexanes/ethyl acetate = 10/1); 1H NMR (500 MHz,
CDCl3) δ 5.46 (m, 0.4H), 4.90 (m, 1H), 2.74 (br s, 0.4H),
2.42-2.31 (m, 0.8H), 2.15-2.02 (m, 1H), 1.99 (m, 4H),
1.52-1.32 (m, 32H), 0.13 (s, 9H, -SiMe3); 13C NMR (125
MHz, CDCl3), characteristic peaks for allene 29l: δ 209.3,
96.0, 82.6, 31.2, 27.3, 27.1, 27.0, 26.8, 26.7, -0.6; 13C NMR
(125 MHz, CDCl3), characteristic peaks for alkene 29l0: δ 143.6,
129.9, 44.5, 33.7, 33.6, 29.6, 29.5, 27.2, 26.3, 26.1, 26.0, 25.2,
25.0, 23.2, 21.9. 29l: HRMS (EI, m/z) [M]þ calcd for C20H38Si
306.2742, found 306.2737. 29l0: HRMS (EI, m/z) [M]þ calcd for
C16H28 220.2191, found 220.2188.
29b: 1:1 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.98 (hexanes/ethyl acetate=10/1); 1H NMR (500 MHz,
CDCl3) δ 4.94 (m, 1H), 4.71 (m, 2H), 2.34 (m, 1H), 2.07-1.18
(m, 4H), 1.73 (m, 3H), 1.36-1.21(m, 2H), 1.17-1.05 (m, 1H),
0.10 (s, 4.5H), 0.07 (s, 4.5H); 13C NMR (125 MHz, CDCl3) δ
205.8, 205.7, 150.1, 150.0, 108.5, 100.4, 83.5, 46.4, 46.1, 36.6,
36.4, 36.3, 36.0, 33.2, 33.1, 31.8, 31.8, 21.0, 20.9, 19.5, 19.4, -0.7,
-0.8; HRMS (EI, m/z) [M]þ calcd for C15H26Si 234.1803, found
234.1811.
29c: colorless liquid; Rf 0.98 (hexanes/ethyl acetate =10/1);
1H NMR (500 MHz, CDCl3) δ 4.94-4.88 (m, 2H), 2.44-2.31
(m, 1H), 2.00-1.75 (m, 3H), 1.31-1.03 (m, 4H), 0.11-0.05 (m,
9H); 13C NMR (125 MHz, CDCl3) δ 208.0, 207.9, 205,8, 205.8,
100.6, 96.4, 96.2, 83.53, 83.43, 83.38, 83.27, 41.8, 41.7, 41.4, 36.9,
36.4, 36.2, 36.0,33.23, 33.17, 32.0, 31.9, 29.7, 19.5, 19.4, 16.9,
16.8, 16.6, 16.5, -0.0, -0.5, -0.7, -0.8; LRMS (EI, m/z)
[M þ H]þ calcd for C19H35Si 319.2, found 319.2
29d: 3:2 mixture of two diastereomers; colorless liquid, vola-
tile; Rf 0.98 (hexanes/ethyl acetate=5/1); 1H NMR (500 MHz,
CDCl3) δ 4.87 (m, 1H), 2.21 (m, 1H), 1.84-1.75 (m, 2H),
1.74-1.67 (m, 1H), 1.67-1.46 (m, 3H), 1.18-1.08 (m, 1H),
1.01-0.89 (m, 7H), 0.88-0.83 (m, 3H), 0.09 (s, 5.4H), 0.07 (s,
3.6H); 13C NMR (125 MHz, CDCl3) δ 206.2, 205.9, 98.7, 98.2,
82.7, 82.6, 46.0, 45.5, 41.0, 40.3, 35.3, 34.8, 34.4, 33.5, 29.7, 29.6,
29.3, 29.2, 27.6, 22.4, 22.2, 22.1, 22.0, 19.3, 18.6, -0.7, -0.9;
HRMS (EI, m/z) [M - H]þ calcd for C15H27Si 235.1882, found
235.1882.
Acknowledgment. We thank NSF (CHE 0955972) for
financial support for this work. The mass spectrometry
facility at UIUC is greatly acknowledged.
29e: colorless liquid; volatile; Rf 0.98 (hexanes/ethyl acetate=
10/1); 1H NMR (500 MHz, CDCl3) δ 4.77 (m, 1H), 2.21 (m, 4H),
1.64-1.54 (m, 8H), 0.09 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
209.4, 96.5, 80.6, 31.7, 29.3, 28.9, -0.6; HRMS (EI, m/z) [M -
H]þ calcd for C12H21Si 193.1413, found 193.1412.
Supporting Information Available: Complete ref 12a and 1H
and 13C NMR spectra for representative compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
29f: colorless liquid; Rf 0.84 (hexanes/ethyl acetate=10/1); 1H
NMR (500 MHz, CDCl3) δ 4.79 (m, 1H), 3.91 (m, 4H),
J. Org. Chem. Vol. 76, No. 4, 2011 1099