10.1002/anie.201914354
Angewandte Chemie International Edition
COMMUNICATION
[1] Davies, H. M. L.; Clarke, D. M.; Thuy K. S. Tetrahedron
Lett. 1985, 26, 5659.
[2] Davies H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1-326.
[3] Stafford, D. G.; Doan, B. D.; Houser, J. H.; Davies, H. M. L. J. Am.
Chem. Soc. 1998, 120, 3326.
[4] Davies H. M. L.; Pelphrey, P. Org. React. 2011. 75, 75-212.
[5] Davies, H. M. L.; Lian, Y. J. Acc. Chem. Res. 2012, 45, 923.
[6] Manning, J. R.; Davies, H. M. L. J. Am. Chem. Soc. 2008, 130, 8602.
[7] Davies, H. M. L.; Saikali, E.; Clark, T. J.; Chee, E. H. Tetrahedron
Lett. 1990. 31, 6299.
[8] Davies, H. M. L.; Hu, B.; Saikali, E.; Bruzinski, P. R. J. Org. Chem.
1994, 59, 4535.
[9] (a) Reviews: Cheng, Q. -Q.; Deng, Y.; Lankelma, L.; Doyle, M. P.
Chem. Soc. Rev. 2017, 46, 5425. (b) Xu, X.; Doyle, M. P. Acc. Chem. Res.
2014, 47, 1396.
[10] Representative examples: (a) Valette, D.; Lian, Y. J.; Haydek, J.
P.; Hardcastle, K. I.; Davies, H. M. L. Angew. Chem., Int. Ed. 2012, 51,
8636. (b) Smith, A. G.; Davies, H. M. L. J. Am. Chem. Soc. 2012, 134,
18241. (c) Deng, Y.; Yglesias, M. V.; Arman H.; Doyle, M. P. Angew.
Chem., Int. Ed. 2016, 55, 10108. (d) Wang, X.; Xu, X.; Zavalij, P. Y.; Doyle,
M. P. J. Am. Chem. Soc. 2011, 133, 16402. (e) Qian, Y.; Xu, X. F.; Wang,
X. C.; Zavalij, P. J.; Hu, W. H. Angew. Chem., Int. Ed. 2012, 51, 5900. (f)
Wang, X. C.; Abrahams, Q. M.; Zavalij, P. J.; Doyle, M. P. Angew. Chem.,
Int. Ed. 2012, 51, 5907. (g) Xu, X.; Zavalij, P. Y.; Doyle, M. P. Angew.
Chem., Int. Ed. 2012, 51, 9829. (h) Xu, X. F.; Zavalij, P. Y.; Doyle, M. P.
Angew. Chem., Int. Ed. 2013, 52, 12664. (i) Xu, X.; Zavalij, P. Y.;
Doyle, M. P. Chem. Commun. 2013, 49, 10287. (j) Qian, Y.; Zavalij, P. Y.;
Hu, W.; Doyle, M. P. Org. Lett. 2013, 15, 1564. (k) Xu, X.; Zavalij, P. Y.;
Doyle M. P. J. Am. Chem. Soc. 2013, 135, 12439. (l) Xu, X.; Zavalij, P. Y.;
Hu, Doyle, J. Org. Chem. 2013, 78, 1583. (m) Xu, X.; Leszczynski, J. S.;
Mason, S. M.; Zavalij, P. Y.; Doyle, M. P. Chem. Commun. 2014, 50,
2462. (n) Jing, C.; Cheng, Q. -Q.; Deng, Y.; Arman, H.; Doyle, M. P. Org.
Lett. 2016, 18, 4550. (o) Cheng, Q. -Q.; Yedoyan, J.; Arman H.; Doyle, M.
P. J. Am. Chem. Soc. 2016, 138, 44. (p) Shved, A. S. Tabolin, A. A.;
Novikov, R. A.; Nelyubina, Y. V.; Timofeev V. P.; Ioffe, S. L. Eur. J. Org.
Chem. 2016, 5569. (q) Guzmán, P. E.; Lian, Y.; Davies, H. M. L. Angew.
Chem., Int. Ed. 2014, 53, 13083. (r) Deng, Y.; Massey, L. A.; Zavalij, P. Y.;
Doyle, M. P. Angew. Chem., Int. Ed. 2017, 56, 7479.
The mechanism of this reaction is consistent with initial attack
occurring at the vinylogous position of the s-trans vinylcarbene
47 as illustrated in Scheme 8. Two recent computational
studies[12] on the [3+2] cycloaddition between vinylcarbenes
and nitrones confirmed our original hypothesis that bulky
catalysts cause preferential attack to occur at the s-trans
11b,c]
configuration of E-vinylcarbenes.[10q,
The initial reaction
occurring on the vinylcarbene in an s-trans configuration,
causes the final product to be a [4+2] cycloadduct rather than a
[4+3] cycloadduct. The observed stereochemistry of these
reactions is consistent with a reaction of 47 proceeding by an
endo transition state occurring at the Re face of the carbene
(when Rh2(R-p-PhTPCP)4 is used as catalyst). Once the attack
has occurred, the resulting vinylrhodium 48 immediately
cyclizes without isomerization to form the cyclohexene 49,
containing a new rhodium carbene.[11c] To complete the
reaction, 49 would need to undergo a 1,2-hydride shift to
generate the final product 50. This final step would be different
from what was seen in the nitrone [3+2] cycloaddition, which
proceeded by a 1,3-hydride shift followed by a proton
transfer.[11c,12]
Scheme 8. Mechanistic model
[11] (a) Lian, Y. J.; Davies, H. M. L. Org. Lett. 2010, 12, 924. (b) Lian,
Y. J.; Davies, H. M. L. Org. Lett. 2012, 14, 1934. (c) Qin, C.; Davies, H. M.
L. J. Am. Chem. Soc. 2013, 135, 14516.
[12] (a) Yang, X.; Yang, Y. S.; Rees, R. J.; Yang, Q.; Tian, Z. Y.; Xue, Y.
J. Org. Chem. 2016, 81, 8082. (b) Ma, L. L.; Wang, W.; Wang G. C. RSC
Advances 2016, 6, 53839.
[13] Guptil, D. M.; Davies, H. M. L. J. Am. Chem. Soc. 2014, 136,
17718.
[14] Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am. Chem. Soc.
2004, 126, 15378.
[15] The relative and absoltue stereochemistry in the formation of
22 is tenatively assigned by analogy to the previous [4+3] cycloaddition
studies (see ref 3), and the observation that the Rh2(S-DOSP)4 catalyst
gives the opposite enantiomer to Rh2(R-p-PhTPCP)4 during the
cyclopropanation stage, as reported in: Negretti, S.; Cohen, C. M.;
Chang, J. J.; Guptil, D. M.; Davies, H. M. L. Tetrahedron. 2015, 71,7415.
[16] The crystal structure has been deposited at the Cambridge
Crystallographic Data Centre, and the deposition number CCDC
1575130 has been allocated.
[17] The absolute configuration of compound 43 has not been
unambiguously determined but is tentatively assigned by analogy to
the X-Ray determined absolute configuration observed for the
cycloaddition products.
This study reveals that the vinylogous reactivity of rhodium-
bound vinylcarbenes can be used to achieve a formal [4+2]
cycloaddition in good yield and excellent enantioselectivity.
The study shows that the vinylogous reactivity is controlled by
multiple factors, including the steric influences of the dirhodium
catalyst as well as the diene. The bulky dirhodium catalysts play
a crucial role in ensuring that the E-vinylcarbene reacts through
the s-trans configuration, which is a requirement for a
successful [4+2] cycloaddition reaction.
ACKNOWLEDGMENT
This work was supported by the National Science Foundation (CHE
1465189). Instrumentation used in this work was supported by the
National Science Foundation (CHE 1531620 and CHE 1626172). We
thank Dr. John Bacsa from Emory university for the X-ray structure
determination.
Keywords: vinylcarbenes, dirhodium, [4+2] cycloaddition,
asymmetric catalysis
This article is protected by copyright. All rights reserved.