5580
J. Am. Chem. Soc. 2001, 123, 5580-5581
Scheme 1
Simultaneous and Stereoselective Construction of
Planar and Axial Centers of Chirality
Louis Fogel, Richard P. Hsung, and William D. Wulff*
Department of Chemistry, Michigan State UniVersity
East Lansing, Michigan 48824
Roger D. Sommer and Arnold L. Rheingold
Department of Chemistry, The UniVersity of Delaware
Newark, Delaware, 19716
ReceiVed January 10, 2001
Atropisomerism resulting from hindered rotation about single
bonds can lead to molecules with centers of axial chirality and
are widely used in asymmetric catalytic synthesis.1 Molecules
containing planar centers of chirality have also been used as chiral
ligands, particularly those containing η6-benzene and η5-cyclo-
pentadienyl complexes.2 To our knowledge, there are no known
synthetic methods that produce both types of chiral centers in a
single step. The reaction of Fischer carbene complexes with aryl
alkynes has the potential for the synthesis of molecules that
contained both planar and axial centers of chirality (Scheme 1).
We report here the first examples of the simultaneous synthesis
of centers of planar and axial chirality and furthermore that this
can be accomplished with high levels of relative diastereoselec-
tion.
Aside from the issue of the stereoselectivity of the benzannu-
lation of carbene complexes with aryl alkynes of the type 2, we
were concerned about the facility of the reaction in general since
the benzannulation of hindered alkynes is known to lead to the
formation of several different types of side products including
indenes and cyclobutanones.3 We were thus delighted to see that
the reaction of complex 1a with alkyne 2a gives good yields of
the arene chromium tricarbonyl complexed product after trapping
of the phenol function with tert-butyldimethylsilyl chloride (Table
1, entries 1 and 2).4 It was quite remarkable to find that either
diastereomer 3a or 4a could be obtained selectively, depending
on the reaction conditions. If tert-butyldimethylsilyl chloride and
Hunig’s base are added at the beginning of the reaction (Method
A, one pot), a 89:11 mixture of isomers is obtained. On the other
hand, if the silylation is performed in a separate step after the
benzannulation reaction is complete (Method B, seq), then a 97:3
selectivity is obtained for the other diastereomer. Similar results
are seen for the reaction of complex 1a with the alkynes 2b, 2c,
and 2d as indicated by the data in Table 1. For the alkynes 2c
and 2d bearing larger groups in the ortho position, the temperature
needs to be increased 120 °C to effect complete conversion to
the thermodynamic products 4c and 4d (entries 6 and 8).
To explain the different stereochemical outcomes of this
reaction, it was reasoned that isomerization about the axial center
may be occurring prior to protection of the phenol with the tert-
butyldimethylsilyl group. Clearly the hydroxyl group would
present less of a steric encumbrance to rotation about the bond
than a tert-butyldimethylsilyloxy group. Thus, under the condi-
tions of Method B, the phenol function remains unprotected until
the completion of the reaction. This provides time for isomer-
ization to the more stable thermodynamic product which is
expected to be the phenol chromium tricarbonyl complex 6 with
the ortho substituent of the alkyne anti to the chromium tricarbonyl
group to minimize steric interactions. If this were true, the kinetic
product must be the phenol complex 5 with the ortho substituent
of the alkyne syn to the metal center. Only the reaction of the
trans-tert-butylvinyl complex 1d gives a stable phenol chromium
tricarbonyl complex. These reactions were performed at 50 °C
in the absence of a trapping agent to give a 65:35 mixture in
favor of 5n, but at 120 °C exclusive formation of 6n is observed.
That the thermodynamic product is the anti product 4 was
confirmed in the reaction of the cyclohexenyl carbene complex
1c with alkyne 2a. In this case, the same isomer predominated
under both the one-pot and the sequential conditions. This
stereoisomer was formed in a 21:79 ratio under the one-pot
conditions at 50 °C (entry 11). Although this mixture of
compounds was slow to isomerize at 50 °C under the conditions
of Method B, it did completely undergo conversion to a single
atropisomer () 1:99) under Method B when the reaction time
was extended to 48 h for the first step (entry 13 vs 12).
Alternatively, complete conversion to 4f could be effected by
raising the temperature to 80 °C (entry 15). The stereochemistry
of the thermodynamic product from this reaction was determined
to be the anti isomer 4f by X-ray diffraction analysis on a single
crystal. The assignment of the thermodynamic isomers obtained
from the reaction of the cyclohexenyl complex 1c with alkynes
2c, 2e, 2d, and 2k were assigned as the anti isomers 4 in analogy
(1) Stanforth, S. P. Tetrahedron, 1998, 54, 263. (b) Bringmann, G.; Walter,
R.; Weirich, R. Angew. Chem., Int. Ed. Engl., 1990, 29, 977. (c) Bringmann,
G.; Breuning, M.; Tasler, S. Synthesis, 1999, 4, 525. (d) Durairaj, K. Curr.
Sci. 1994, 66, 833. (e) Bringmann, G.; Walter, R.; Weirich, R. In Methods of
Organic Chemistry (Houben Weyl), 4th ed.; Helmchen, G., Hoffmann, R. W.,
Mulzer, J., Schaumann, E., Eds.; Thieme, Stuttgart, 1995; Vol. E21a, p 567.
(2) Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic
Molecules; University Science Books: Mill Valley, CA, 1994; Chapter 10
and references therein. (b) Uemura, M. I. In Stereochemistry of Organometallic
and Inorganic Compounds; Zanello, P.; Ed., Elsevier: Amsterdam, 1994; Vol.
5, p 507. (c) Togni, A., Hayashi, T., Eds. Ferrocenes, Homogeneous Catalysis,
Organic Synthesis; Material Science, VCH: Weinheim, 1995. (d) Fu, G. C.
Acc. Chem. Res. 2000, 33, 412.
1
with 4f and by H NMR correlation with 4f. For all of these
alkynes, the reaction products could be completely isomerized
to the anti isomer by performing the reaction at 120 °C except
for the smaller ortho methoxyl complex which only required 50
°C for complete conversion. This includes the very hindered tert-
butyl complex 3i which was formed as a slightly preferred kinetic
product having the syn stereochemistry which was determined
by X-ray diffraction. The reactions of the alkynes 2g and 2h with
complex 1c gave a single diastereomer with the one-pot conditions
of Method A at 50 °C, and thus it was not possible to determine
if the observed isomer is also the thermodynamic isomer.
Therefore, the assignment of the stereochemistry of 4l and 4m
was determined by X-ray diffraction analysis of a single crystal.
While high selectivities could be obtained for the thermody-
namic anti product from the reactions of all of the carbene
(3) For recent reviews on the chemistry of carbene complexes, see: (a)
Wulff, W. D. In ComprehensiVe Organometallic Chemistry II, Abel, E. W.,
Stone, R. G. A., Wilkinson, G., Eds.; Pergamon Press: Elmsford, NY, 1995;
Vol. 12, p 469. (b) Bernasconi, C. F. Chem. Soc. ReV. 1997, 26, 299. (c)
Hegedus, L. S. Tetrahedron 1997, 53, 4105. (d) Wulff, W. D. Organometallics
1998, 17, 3116. (e) Do¨tz, K. H.; Tomuschatt, P., Chem. Soc. ReV. 1999, 28
187. (f) Herndon, J. W. Coord. Chem. ReV. 1999, 181, 177. (g) Do¨rwald, F.
Z. Metal Carbenes in Organic Synthesis; Wiley-VCH: Weinheim, New York,
1999.
(4) Chamberlin, S.; Wulff, W. D.; Bax, B. Tetrahedron 1993, 49, 5531.
10.1021/ja010091f CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/16/2001
Fogel
