Stereochemical probes of intramolecular C-H insertion reactions of iron- carbene complexes [11]

Full text of DOI:10.1021/ja000239f

J. Am. Chem. Soc. 2000, 122, 5897-5898
5897
Table 1. Stereochemical Probes of Intramolecular Iron-Carbene
C-H Insertion Reactions
Stereochemical Probes of Intramolecular C-H
Insertion Reactions of Iron-Carbene Complexes
Shingo Ishii, Shikai Zhao, and Paul Helquist*
Department of Chemistry and Biochemistry
251 Nieuwland Science Hall, UniVersity of Notre Dame
Notre Dame, Indiana 46556
ReceiVed January 24, 2000
A common characteristic of carbenes and metal-carbene
complexes is their propensity to undergo insertion reactions into
O-H, N-H, and C-H bonds.1 Several forms of intramolecular
C-H insertions, including enantioselective versions, have been
developed for the construction, most importantly, of cyclopentanes
and five-membered heterocycles. The importance of these reac-
tions is reflected by their widespread use in synthesis.
We have reported the use of (η5-cyclopentadienyl)(dicarbonyl)-
iron-carbene complexes, [(C5H5)(CO)2FedCHR]+ X-, in intra-
molecular C-H insertion reactions,2,3 and we have employed these
reactions in natural product syntheses.4 A few related reactions
of iron complexes have been reported by other workers.5 However,
a detailed understanding of the stereochemistry of these reactions
is needed before more elaborate applications are pursued. We
now report our studies of key stereochemical features of iron-
carbene insertions.
Useful scaffolds for these reactions are obtained by copper-
promoted 1,4-addition of Grignard reagents to cyclohexenone
followed by enolate alkylation with thiocarbene complex 16
(Scheme 1).2 S-Methylation of the thioalkyliron derivatives 2 with
Scheme 1
a Substrates and products were racemic unless otherwise indicated.
b Products were formed as one major diastereomer (g90%) unless
otherwise indicated. c Substrate and product were obtained stereose-
trimethyloxonium tetrafluoroborate7 and loss of thioanisole gener-
ate carbene complexes 3. Intramolecular C-H insertion produces
d
lectively in the major enantiomeric form shown. ∼5-10% of dia-
stereomeric product detected by 13C NMR; see footnote 8.
(1) For reviews of carbenes, carbene complexes, and insertion reactions,
see: (a) Doyle, M. P. Chem. ReV. 1986, 86, 919. (b) Maas, G. Top. Curr.
Chem. 1987, 137, 75. (c) Taber, D. F. In ComprehensiVe Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Pattenden, G., Vol. Ed.; Pergamon Press:
Oxford, 1991; Vol. 3, pp 1045-1062. (d) Adams, J.; Spero, D. M. Tetrahedron
1991, 47, 1765-1808. (e) Padwa, A.; Krumpe, K. E. Tetrahedron 1992, 48,
5385-5453. (f) Ye, T.; McKervey, M. A. Chem. ReV. 1994, 94, 1091-1160.
(g) Doyle, M. P. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W.; Stone, F. G. A.; Wilkinson, G.; Hegedus, L. S., Eds.; Pergamon: Oxford,
1995; Vol. 12, pp 421-468. (h) Doyle, M. P.; McKervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds:
from Cyclopropanes to Ylides; Wiley: New York, 1998. (i) AdVances in
Carbene Chemistry; Brinker, U., Ed.; JAI Press: Stamford, CT, 1998; Vol.
2. (j) Sulikowski, G. A.; Cha, K. L.; Sulikowski, M. M. Tetrahedron:
Asymmetry 1998, 9, 3145-3169.
fused cyclopentanes 4. We have chosen several side chains (Table
1) to probe the stereochemical outcome of the cyclization.
The observation that a simple alkyl side chain (entry a) results
in the formation of a mixture of diastereomers, whereas more
sterically demanding (and perhaps electronically perturbing)
2-arylethyl (entries b and c) and 3-(trimethylsilyl)propyl (entry
d) side chains occur with high diastereoselectivity8 is important
in planning applications of this procedure, but this observation is
(6) (a) Knors, C.; Kuo, G.-H.; Lauher, J. W.; Eigenbrot, C.; Helquist, P.
Organometallics 1987, 6, 988-995. (b) Knors, C.; Helquist, P. Organomet.
Synth. 1988, 4, 205-209.
(2) (a) Zhao, S.-K.; Knors, C.; Helquist, P. J. Am. Chem. Soc. 1989, 111,
8527-8528. (b) Ishii, S.; Helquist, P. Synlett 1997, 508-510.
(3) For reviews of iron-carbene complexes, see: (a) Brookhart, M.;
Studabaker, W. B. Chem. ReV. 1987, 87, 411. (b) Helquist, P. In AdVances in
Metal-Organic Chemistry; Liebeskind, L. S., Ed.; JAI Press: London, 1991;
Vol. 2, pp 143-194. (c) Fatiadi, A. J. J. Res. Natl. Inst. Stand. Technol. 1991,
96, 1-113. (d) Petz, W. Iron-Carbene Complexes; Springer-Verlag: Berlin,
1993. (e) Guerchais, V. Bull. Soc. Chim. Fr. 1994, 131, 803-811. (f) Ruck-
Braun, K.; Mikulas, M.; Amrhein, P. Synthesis 1999, 727-744.
(4) (a) Zhao, S.-K.; Helquist, P. J. Org. Chem. 1990, 55, 5820-5821. (b)
Zhao, S.; Mehta, G.; Helquist, P. Tetrahedron Lett. 1991, 32, 5753-5756.
(5) (a) Guerchais, V.; Sinbandhit, S. J. Chem. Soc., Chem. Commun. 1990,
1550-1552. (b) Scharrer, E.; Brookhart, M. J. Organomet. Chem. 1995, 497,
61-71.
(7) Meerwein, H. Organic Syntheses; Baumgarten, H. E., Ed.; Wiley: New
York, 1973; Collect. Vol. V, pp 1096-1103.
(8) Stereoisomeric compositions were determined by 1H and 13C NMR
having lower limits of detection of minor isomers of ∼5-10%. Several
stereochemical assignments are based upon nOe studies. Details are in the
Supporting Information. The structure of 4b was confirmed by X-ray
diffraction. In entries g and h of Table 1, small amounts ( ∼5-10%) of the
diastereomeric products 4h and 4g were detected by 13C NMR.; they were
likely due to non-diastereomerically pure precursors rather than actual
crossover during the insertion reactions. The locations of the isotopic labels
in products 4i-l were determined by comparison of 1H and 13C NMR spectra
of these compounds and their separately prepared, non-deuterated counterparts.
10.1021/ja000239f CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/06/2000

5898 J. Am. Chem. Soc., Vol. 122, No. 24, 2000
Communications to the Editor
not particularly revealing with respect to more subtle, mechanisti-
cally related, stereochemical aspects of this reaction. More
informative are the results obtained with substrates having two
different substituents at the insertion sites. Substrates 2e and 2f
were prepared with the depicted absolute configurations (entries
e and f).9 Subsequent insertion reactions gave stereoisomers 4e
and 4f as the major cyclization products with g90% diastereo-
selectivity.8 Entries g and h serve as especially sensitive probes
of stereochemistry whereby the CH3 and CD3 groups have
essentially identical steric requirements but yet the isotopically
diastereomeric substrates 2g and 2h give the diastereomeric
products 4g and 4h, respectively, with ∼90% stereoselectivity.8
The deuterium-labeled substrates in entries i through l serve as
probes of the origin of the participating hydrogen atom and its
location in the insertion products.8
Deuterium-labeled 5 was prepared (eq 1) as a preliminary probe
of primary kinetic isotope effects. Cyclization followed by base-
catalyzed equilibration of cis and trans products gave 6 and 7 in
a ratio of approximately 2.7:1 (eq 2).10 This internal competition
experiment suggests a primary isotope effect of this magnitude.
This value must be regarded cautiously as a tentative estimate
due to possible stereochemical complications of preparing a
substrate 5 having three stereogenic centers without a good
measure or good control of the actual diastereomeric composition.
each case. In entry f, the p-methoxyphenyl substituent may have
been anticipated to provide extra stabilization and therefore a
longer lifetime for a carbocationic intermediate that again could
have undergone bond rotation, leading to a mixture of diastere-
omeric products,13 but the reaction was highly diastereoselective.
In entry d, â-silicon stabilization of a carbocationic intermediate
and subsequent elimination of the silyl group may have been
expected to generate an alkene side product, which was not seen.
The tentative estimate of a primary kinetic isotope effect of
approximately 2.7 is in good agreement with values that are most
typically in the range 1.6-4.2 for related insertion reactions of
carbenes11a-c,d,f,g,i,j and in the range 1.2-3.1 for metal-catalyzed
insertions of diazo compounds or reactions of preformed metal-
carbene complexes.12c,h,u In some cases of stepwise radical
pathways, larger values have been reported for carbene insertions.11g
The relatively small kinetic isotope effect seen in the present work
suggests only a modest extent of net C-H bond breaking in the
transition state. More rigorous studies will be necessary before
drawing firmer conclusions.
Intramolecular C-H insertion reactions of iron-carbene com-
plexes provide a highly stereoselective route to cyclopentanes.
The results of this study will permit applications in synthesis for
which a given stereochemical outcome can be planned with a
high level of confidence. Attractive further goals are to develop
more cost-effective catalytic reactions, even though iron is inex-
pensive, and to develop asymmetric versions of these reactions.
Acknowledgment. We thank Professors Per-Ola Norrby and Xavier
Creary for helpful discussions, Donald Schifferl and Dr. Jaroslav Zajicek
for NMR assistance, Dr. Kenneth J. Haller for X-ray studies, and Dr.
Bruce Plashko, Mr. David Griffith, and Dr. William Bogess for mass
spectrometry assistance. We are grateful for financial support from the
National Science Foundation and the University of Notre Dame. S. I. is
grateful for a Reilly Fellowship.
Supporting Information Available: Experimental procedures and
selected NMR spectra for precursors, cyclization substrates, and products
(PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
Previous studies of C-H insertion reactions of carbenes and
metal-carbene complexes suggest that they often occur by
concerted, one-step pathways, although stepwise mechanisms may
apply in some cases whereby transfer of hydrogen produces
charged or radical intermediates followed by separate radical or
dipolar recombination.1,11,12 The concerted pathway has commonly
been invoked for metal-catalyzed cyclizations of diazocarbonyl
compounds which most likely occur via metal-carbene com-
plexes.1,12 Taken as a set, our results can best be accommodated
by a one-step, concerted insertion of an iron-carbene complex
into a properly situated C-H bond via a chair-like, cyclic
transition state 8 (Scheme 2).
JA000239F
(11) (a) Ring, D. F.; Rabinovitch, B. S. Can. J. Chem. 1968, 46, 2435-
2450. (b) Baer, T. A.; Gutsche, C. D. J. Am. Chem. Soc. 1971, 93, 5180-
5186. (c) Barcus, R. L.; Hadel, L. M.; Johnston, L. J.; Platz, M. S.; Savino,
T. G.; Scaiano, J. C. J. Am. Chem. Soc. 1986, 108, 3928-3937. (d) Savino,
T. G.; Kanakarajan, K.; Platz, M. S. J. Org. Chem. 1986, 51, 1305-1309. (e)
Oku, A.; Harada, T.; Hattori, K.; Nozaki, Y.; Yamaura, Y. J. Org. Chem.
1988, 53, 3089-3098. (f) Pascal, R. A., Jr.; Mischke, S. J. Org. Chem. 1991,
56, 6954-6957. (g) Kirmse, W.; O¨ zkir, I. S.; Schnitzler, D. J. Am. Chem.
Soc. 1993, 115, 792-793. (h) Miebach, T.; Wu¨ster, H.; Brinker, U. H. J.
Org. Chem. 1993, 58, 6520-6523. (i) Moss, R. A.; Liu, W. Tetrahedron Lett.
1996, 37, 279-282. (j) Moss, R. A.; Yan, S. Tetrahedron Lett. 1998, 39,
9381-9384. (k) Moss, R. A.; Yan, S. Org. Lett. 1999, 1, 819-822.
(12) (a) Taber, D. F.; Ruckle, R. E., Jr. J. Am. Chem. Soc. 1986, 108, 7686-
7693. (b) Fischer, H.; Schmid, J. J. Mol. Catal. 1988, 46, 277-285. (c)
Demonceau, A.; Noels, A. F.; Costa, J.-L.; Hubert, A. J. J. Mol. Catal. 1990,
58, 21-26. (d) Wang, S. L. B.; Su, J.; Wulff, W. D.; Hoogsteen, K. J. Am.
Chem. Soc. 1992, 114, 10665-10666. (e) Spero, D. M.; Adams, J. Tetrahedron
Lett. 1992, 33, 1143-1146. (f) Doyle, M. P.; Westrum, L. J.; Wolthuis, W.
N. E.; See, M. M.; Boone, W. P.; Bagheri, V.; Pearson, M. M. J. Am. Chem.
Soc. 1993, 115, 958-964. (g) Aumann, R.; La¨ge, M.; Krebs, B. Chem. Ber.
1994, 127, 731-738. (h) Wang, P.; Adams, J. J. Am. Chem. Soc. 1994, 116,
3296-3305. (i) Pirrung, M. C.; Morehead, A. T., Jr. J. Am. Chem. Soc. 1994,
116, 8991-9000. (j) Doyle, M. P.; Dyatkin, A. B.; Autry, C. I. J. Chem.
Soc., Perkin Trans. 1 1995, 619-621. (k) Taber, D. F.; You, K. K.; Rheingold,
A. L. J. Am. Chem. Soc. 1996, 118, 547-556. (l) Barluenga, J.; Rodr´ıguez,
F.; Vadecard, J.; Bendix, M.; Fan˜ana´s, F. J.; Lo´pez-Ortiz, F. J. Am. Chem.
Soc. 1996, 118, 6090-6091. (m) Taber, D. F.; Song, Y. J. Org. Chem. 1996,
61, 6706-6712. (n) Barluenga, J.; Aznar, F.; Fernandez, M. Chem. Eur. J.
1997, 3, 1629-1637. (o) Clark, J. S.; Dossetter, A. G.; Russell, C. A.;
Whittingham, W. G. J. Org. Chem. 1997, 62, 4910-4911. (p) Takeda, K.;
Okamoto, Y.; Nakajima, A.; Yoshii, E.; Koizumi, T. Synlett 1997 1181. (q)
Wang, J.; Chen, B.; Bao, J. J. Org. Chem. 1998, 63, 1853-1862. (r) Wang,
J.; Liang, F.; Chen, B. J. Org. Chem. 1998, 63, 8589-8594. (s) Barluenga,
J.; Rodr´ıguez, F.; Vadecard, J.; Bendix, M.; Fan˜ana´s, F. J.; Lo´pez-Ortiz, F.;
Rodr´ıguez, M. A. J. Am. Chem. Soc. 1999, 121, 8776-8782. (t) White, J. D.;
Hrnciar, P. J. Org. Chem. 1999, 64, 7271-7273. (u) Sulikowski, G. A.; Lee,
S. Tetrahedron Lett. 1999, 40, 8035-8038.
Scheme 2
A stepwise pathway involving an internal hydride transfer to
form a carbocation intermediate 9 appears to be untenable due to
the expected rapid carbon-carbon single bond rotation that would
produce a mixture of diastereomeric products (Scheme 3). In the
Scheme 3
cases of entries g and h, these rotations would have led to mixtures
of products 4g and 4h having essentially equal stabilities, but
these products were obtained with ∼90% diastereoselectivity in
(9) Stereoselective syntheses of these substrates are described in the
Supporting Information.
(10) This experiment was performed four times to give a product ratio of
2.7 ( 0.3.
(13) Brookhart, M.; Kegley, S. E.; Husk, G. R. Organometallics 1984, 3,
650-652.