Tandem lithium-ene cyclization and thiophenoxide expulsion to produce fused vinylcyclopropanes: First observation of allylic lithium oxyanion- induced reactivity and stereoselectivity in intramolecular carbolithiation

Full text of DOI:10.1021/ja993325s

412
J. Am. Chem. Soc. 2000, 122, 412-413
Scheme 1
Tandem Lithium-Ene Cyclization and
Thiophenoxide Expulsion to Produce Fused
Vinylcyclopropanes: First Observation of Allylic
Lithium Oxyanion-Induced Reactivity and
Stereoselectivity in Intramolecular Carbolithiation
Table 1. Tandem Cyclizations to Fused Vinylcyclopropanesa
Dai Cheng, Kevin R. Knox, and Theodore Cohen*
Department of Chemistry
UniVersity of Pittsburgh
Pittsburgh, PennsylVania 15260
ReceiVed September 14, 1999
We reveal herein the first synthetic method based on the rarely
used but surprisingly facile lithium-ene cyclization1 followed by
thiophenoxide expulsion to yield fused vinylcyclopropanes. In
addition, we present the first observation of the remarkable effect
of allylic lithium oxyanion-induced reactivity and stereoselectivity
on an intramolecular carbometalation, illustrated by an efficient,
highly stereoselective synthesis of a natural bicyclo[3.1.0]hexane.
The lithium-ene cyclization is facile, but the products are
usually those formed in a subsequent irreversible process.1 We
now show that the easily prepared substrates used in the prior
study1 can be deprotonated to generate the allyllithiums for the
tandem cyclizations. In the present work, the required irreversible
step that undoubtedly drives the lithium-ene cyclization to
completion is expulsion of a thiophenoxide ion, a process
previously revealed in this laboratory as a powerful cyclopropane
synthesis.2,3
The basic protocol (Scheme 1) involves deprotonation of allyllic
phenyl thioethers such as 14 by LIC-KOR.5,6 To obtain high yields
of the cyclization product, transmetalation with LiBr is required,
presumably because of the high basicity of organopotassiums.
Conversion of the resulting allyllithium 2 to the monocyclic
intermediate 3 is strikingly efficient, considering the charge
localization in the latter and the great stabilization of the anionic
group by resonance and by sulfur. Intramolecular displacement
of the thiophenoxide ion2,3 forms the fused vinylcyclopropane 4.
The yield is quantitative in the formation of the five-membered
ring from the substrate in which both alkene functions are
monosubstituted (Table 1). Alkyl substituents at all positions of
the alkenes except the terminus of the enophile are tolerated well.
The formation of fused 6,3-systems was also successful, but
attempts to obtain fused 4,3- and 7,3-systems were not.
a See Supporting Information for detailed experimental procedures
and compound characterizations. b Isolated yields after chromatography.
c A mixture of two diastereomers.
limited efficiency and generality.7 Interestingly, this technique
apparently has not been applied to intramolecular carbometala-
tions, presumably because of incompatibilities and regiochemical
difficulties in generating the dianions.8 However, successful
generation of the requisite dianions by deprotonation could allow,
for the first time, allylic lithium oxyanion-facilitated anionic
cyclizations.10
To provide more functionality and to increase the reactivity
so that compounds such as 11 could be induced to react, an allylic
hydroxyl group was introduced into the enophile. A number of
intermolecular carbolithiations and carbomagnesiations are fa-
cilitated by an allylic Li or Mg oxyanionic group, although with
(1) Cheng, D.; Zhu, S.; Liu, X.; Norton, S. H.; Cohen, T. J. Am. Chem.
Soc. 1999, 121, 10241-42.
(2) Cohen, T.; Matz, J. R. J. Org. Chem. 1979, 44, 4816-18 and references
therein.
(3) The intermolecular analogue of this tandem alkene carbolithiation/
cyclization requires a more nucleophilic anion and a more active alkene:
Cohen, T.; Weisenfeld, R. B.; Gapinski, R. E. J. Org. Chem. 1979, 44, 4744-
46. Cohen, T.; Sherbine, J. P.; Mendelson, S. A.; Myers, M. Tetrahedron
Lett. 1985, 26, 2965-68. Schaumann, E.; Friese, C.; Spanka, C. Synthesis
1986, 1035-1037. Tanaka, K.; Funaki, I.; Kanemasa, S.; Kobayashi, H.;
Tanaka, J.; Tsuge, O. Bull. Chem. Soc. Jpn. 1988, 61, 3957-64. Se
analogue: Krief, A.; Barbeaux, P.; Guittet, E. Synlett 1990, 509-10. The
single intramolecular case involves selenide displacement: Krief, A.; Bar-
beaux, P. Tetrahedron Lett. 1991, 32, 417-420.
(4) The enophile chain was readily incorporated into the substrate by
alkylation of the organolithium generated by deprotonation of an allyllic phenyl
thioether.1
(5) Schlosser, M. In Modern Synthetic Methods 1992; Scheffold, R., Ed.;
VCH: New York, 1992; pp 227-271, see especially ref 3.
(6) An alkyllithium base deprotonates sluggishly and undergoes some SN2′
displacement of thiophenoxide.
(7) Reviews: Klumpp, G. W. Recl. TraV. Chim. Pays-Bas 1986, 105, 1-20.
Vara Prasad, J. V. N.; Pillai, C. N. Organometallics 1983, 259, 1-30. Marek,
I.; Normant, J.-F. In Metal Catalyzed Cross Coupling Reactions; Diederich,
F., Stang, P., Eds.; Wiley VCH: New York, 1998; pp 269-335.
(8) For example, the organometallic is usually prepared from an alkyl
halide9 which would form a cyclic ether in the presence of the oxyanionic
group. In addition, in the case of Mg-ene cyclizations (Oppolzer, W. Angew.
Chem., Int. Ed. Engl. 1989, 28, 38-52), the allyl halide is produced from an
allylic alcohol, thus presenting a regiochemical problem.
(9) Review: Bailey, W. F.; Ovaska, T. V. In AdVances in Detailed Reaction
Mechanisms; Coxon, J. M., Ed.; JAI Press: Greenwich, CT, 1994; Vol. 3, p
251-273.
(10) Reductive lithiation, another technique that allows the presence of
oxyanionic functions, was used in the first examples of intramolecular
oxyanion-facilitated addition of unstabilized organolithiums to alkenes;
however, the oxyanionic group was in the vicinity of the carbanion rather
than the alkene. Mudryk, B.; Cohen, T. J. Am. Chem. Soc. 1993, 115, 3855-
65. Chen, F.; Mudryk, B.; Cohen, T. Tetrahedron 1994, 50, 12793-12810.
10.1021/ja993325s CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/23/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 413
Scheme 2
diastereomer.12 Finally, 28 generated the fused 6,3-system 29 in
high yield with the same stereoselectivity.12
The first synthetic procedure based on the lithium-ene
cyclization has led to a very efficient method for the production
of vinylcyclopropanes. The latter constitute a particularly useful
class of compounds that includes the large group of pyrethroid
insecticides,15 as well as other natural products, and that can be
transformed into still others as illustrated above. Furthermore,
they are particularly versatile,16 undergoing the widely used
vinylcyclopropane-to-cyclopentene ring expansion,17 [2 + 5] and
[2 + 3] cycloadditions to alkenes,18 and ring-opening additions.19
The present method of generation of fused vinylcyclopropanes
is particularly efficient when compared to extant methods,17b,20
given the ease of preparation of the cyclization substrates. Of
great significance is the first use of an allylic lithium oxyanionic
group to enhance reactivity and control stereochemistry in an
anionic cyclization. Compared with the intermolecular version,7
the intramolecular version demonstrates remarkably enhanced
reactivity and stereoselectivity. For example, the intermolecular
allyllithiation of an allyl alcohol21 proceeded with only 2:1
stereoselectivity, in the same sense. If, as appears likely, allylic
lithium oxyanionic substituents greatly enhance the scope of
anionic cyclizations in general,9,10 this effect holds considerable
potential for new strategies in ring synthesis.
Scheme 3
Two suitable substrates, 23a,b, were readily prepared as shown
in Scheme 2.11 Happily, not only were the cyclizations of 23a,b
to 24a,b greatly facilitated, occurring at room temperature rather
than the reflux temperature required in the absence of allylic
hydroxy groups (Scheme 1), but they also proceeded in high yields
and were completely stereoselective as determined by chromato-
graphic and NMR spectroscopic behavior. Their diimide reduction
products 25a,b were shown to have the hydroxyl and cyclopropyl
rings cis.12
This is the most efficient synthesis of cis-sabinene hydrate 25b,
a terpene of the thujane class.14 It avoids the addition of MeLi to
the corresponding ketones, a common strategy of previous
syntheses, which results in a mixture of E- and Z-isomers.14 The
flexibility of the method is illustrated by the preparation of 25a
which constitutes a formal synthesis of sabinaketones, sabinene,
cis- and trans-sabinene hydrates, 2-thujene, umbellulone, etc., all
of which have been prepared from 25a.14a
Acknowledgment. We thank the National Science Foundation for
support of this work, Professor Fu-Tyan Lin for help in NMR analysis,
Ms. Margarete Bower for literature searches, and Professor Peter Wipf
and Dr. David A. Mareska for helpful discussions.
Supporting Information Available: Experimental procedures and
details of compound characterization are provided (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA993325S
(15) Crombie, L. Pyrethrum Flowers; Casida, J. E., Quistad, G. B., Ed.;
Oxford: New York, 1995; Chapter 8.
(16) Reissig, H.-U. The Chemistry of the Cyclopropyl Group; Patai, S.,
Rappoport, Z., Eds.; Wiley: Chichester, 1987; Part 1, pp 416-430.
(17) (a) Review: Hudlicky, T.; Reed, J. W. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5,
pp 899-970. (b) Rearrangement of fused vinylcyclopropane systems similar
to those prepared in the present paper: Baldwin, J. E.; Burrell, R. C. J. Org.
Chem. 1999, 64, 3567-71.
The facilitating effect of the lithium oxyanionic group was
further demonstrated by the successful double cyclization of 26
(Scheme 3), an allylically hydroxylated analogue of 11 which,
itself, failed to cyclize. Impressively, 27 was formed as a single
(18) Wender, P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A.
J. Am. Chem. Soc. 1999, 121, 5348-49 and references therein. Feldman, K.
S.; Romanelli, A. L.; Ruckle, J. R. E. J. Org. Chem. 1992, 57, 100-110 and
references therein. Jung, M. E.; Rayle, H. L. J. Org. Chem. 1997, 62, 4601-
09.
(19) One of the more general and useful ones: Alpoim, M. C. M. de C;
Morris, A. D.; Motherwell, W. B.; O’Shea, D. M. Tetrahedron Lett. 1988,
29, 4173-76.
(11) Epoxide alkylation: Keck, G. E.; Enholm, E. J. Tetrahedron Lett. 1985,
26, 3311-14. Li-I exchange: Bailey, W. F.; Punzalan, E. R. J. Org. Chem.
1990, 55, 5404-06. Diimide reduction: Carey, F. A.; Sundberg, R. J.
AdVanced Organic Chemistry; Plenum Press: New York, 1990; Vol. 2, p
230.
(12) The E-structures were assigned to 25a,b, 27, and 29 by comparisons
with known compounds, NOE studies, and Simmons-Smith cyclopropanation
of the corresponding allylic alcohols, a reaction which is cis-selective with
regard to the hydroxyl group.13
(13) Poulter, C. D.; Friedrich, E. C.; Winstein, S. J. Am. Chem. Soc. 1969,
91, 6892-94 and references therein.
(14) (a) Thomas, A. F. In The Total Synthesis of Natural Products;
ApSimon, J., Ed.; John Wiley & Sons: New York, 1973; Vol. 2, pp 145-
148. (b) Fanta, W. I.; Erman, W. F. J. Org. Chem. 1968, 33, 1656-58. Gaoni,
Y. Tetrahedron 1972, 28, 5525-31.
(20) For a summary of synthetic methods for vinylcyclopropanes, see:
Schaumann, E.; Kirschning, A.; Narjes, F. J. Org. Chem. 1991, 56, 717-723
and references 6-10 cited therein. Newer methods of production of fused
vinylcyclopropanes based on the transition metal cyclization of enynes:
Harvey, D. F.; Lund, K. P.; Neil, D. A. J. Am. Chem. Soc. 1992, 114, 8424-
34. Oppolzer, W.; Pimm, A.; Stammen, B.; Hume, W. E. HelV. Chim. Acta
1997, 80, 623-639. Montchamp, J.-L.; Negishi, E.-I. J. Am. Chem. Soc. 1998,
120, 5345-46.
(21) Felkin, H.; Swierczewski, G.; Tambute´, A. Tetrahedron Lett. 1969,
707-10.