C O M M U N I C A T I O N S
Table 2. Asymmetric Hydroboration of 3,3-Disubstituted Cyclopropenes
substrate
1
2
3
a
b
R
R
R
ligand
cis/trans
yield, %
ee, %
abs.config.
[R]D
1
2
3
4
5
6
Me
TMS
Ph
COOMe
Me
COOMe
COOEt
COOMe
COOMe
CH2OMe
COOMe
H
1b
1c
1d
1e
1f
(R)-BINAP
(R)-BINAP
>99:1
>99:1
>99:1
-
>99:1
-
94
99
99
99
98
94
97
1S,2R
1R,2R
1S,2R
2S
1R,2S
-
-32.9
-31.9
-57.5
+65.2
+38.8
-
H
H
H
H
(R)-BINAP
92
(S)-Tol-BINAPc
(R,R)-Et-BPEc
(R)-BINAP
>98d
87
COOMe
n-Bu
1g
0e
-
a Isolated yield. b Enantiomeric excess was determined by GC analysis using CYCLODEX B or CYCLOSIL B chiral columns. c Reaction was performed
in DCM (1 M). d Determined by NMR with Eu(hfc)3. e Cyclopropene 1g rearranged into a corresponding furan in 1 h at room temperature.
Table 3. Suzuki Cross-Coupling Reaction of cis-4b and cis-4f
M.-H. Angew. Chem., Int. Ed. 1998, 37, 2845. (b) Chen, H.; Deng, M.-Z.
J. Org. Chem. 2000, 65, 4444. (c) Yao, M.-L.; Deng, M.-Z. J. Org. Chem.
2000, 65, 5034. (d) Chen, H.; Deng, M.-Z. Org. Lett. 2000, 2, 1649. (e)
Charette, A. B.; De Freitas-Gil, R. P. Tetrahedron Lett. 1997, 38, 2809.
(f) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 2000, 65, 9194. For
Matteson homologation, see: (g) Pietruszka, J.; Witt, A. Perkin 1 2000,
4293. See also ref 1f. For oxidation into cyclopropanols, see for
example: (h) Bubnov, Yu. N.; Nesmeyanova, O. A.; Rudashevskaya, T.
Yu.; Mikhailov, B. M.; Kazansky, B. A. Tetrahedron Lett. 1971, 12, 2153.
(i) Luithle, J. E. A.; Pietruszka, J. Eur. J. Org. Chem. 2000, 2557.
with Aryl and Vinyl Iodides13
2
R
R
time, h
yield,%
(2) For direct metalation of cyclopropanes, see: (a) Lohr, S.; De Meijere, A.
Synlett 2001, 489. (b) Priestley, E. S.; Decicco, C. P. Org. Lett. 2000, 2,
3095. For 1,3-cyclization, see: (c) Matteson, D. S.; Schaumberg, G. D.
J. Org. Chem. 1966, 31, 726. For addition of dihalocarbene to vinylbo-
ronates, see: (d) Woods, W. G.; Bengelsdorf, I. S. J. Org. Chem. 1966,
31, 2769. For Pd-catalyzed addition of diazomethane to vinylboronates,
see: (e) Marko´, I. E.; Giard, T.; Sumida, S.; Gies, A.-E. Tetrahedron
Lett. 2002, 43, 2317. (f) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem.
1999, 64, 8287. See also refs 1g,i. For Simmons-Smith cyclopropanation,
see: (g) Imai, T.; Mineta, H.; Nishida, S. J. Org. Chem. 1990, 55, 4986.
See also refs 1g,i, 2e. For allylboration of cyclopropenes, see for
example: ref 1h. For noncatalytic hydroboration of methylenecyclopro-
panes, see: (h) Utimoto, K.; Tamura, M.; Tanouti, M.; Sisido, K.
Tetrahedron 1972, 28, 5697.
1
2
3
4
5
6
COOMe (b)
COOMe (b)
COOMe (b)
COOMe (b)
COOMe (b)
CH2OMe (f)
Ph (1S,2S-5)
1
1
1
1
0.5
7
76
77
64
85
65
85
p-MeOC6H4 (1S,2S-6)
p-MeO2CC6H4 (1S,2S-7)
1-Nphth (1S,2S-8)
CHdC(Me)Ph (1S,2S-9)
Ph (1R,2R-10)
the reaction conditions tested, trisubstituted cyclopropene 1g did
not undergo hydroboration at all due to very facile rearrangement
into a corresponding furan derivative (entry 6).10
To demonstrate the synthetic utility of the obtained cyclopropyl
boronates, compounds cis-3b and cis-3f were tested in the Suzuki
cross-coupling reaction with aryl and vinyl iodides. Employment
of sterically encumbered 3 in this process poses a certain challenge
since no examples of Suzuki-coupling with cis-substituted cyclo-
propylboronic derivatives were reported to date. Although the
boronic esters failed to undergo cross-coupling, the corresponding
boronic acids 4b,f11 provided good yields of desired products in
the presence of Fu’s catalyst system12 (eq 4, Table 3).
In summary, we have demonstrated that enantiopure 2,2-
disubstituted cyclopropyl boronates could be easily synthesized via
the catalytic asymmetric hydroboration of 3,3-disubstituted cyclo-
propenes. It was shown that ester and alkoxymethyl substituents
serve as effective directing groups in the hydroboration reaction.
A directing effect was found to be necessary for achieving high
degrees of enantioselectivity. The synthetic usefulness of this
methodology was demonstrated in the effective synthesis of
optically active trisubstituted aryl- and vinylcyclopropanes.
(3) For iron-catlyzed addition of Grignard and alkylzinc reagents to cyclo-
propenone acetals, see: (a) Nakamura, M.; Hirai, A.; Nakamura, E. J.
Am. Chem. Soc. 2000, 122, 978. For Cu-catalyzed addition of Grignard
reagents to cyclopropenes, see: (b) Liao, L.; Fox, J. M. J. Am. Chem.
Soc. 2002, 124, 14322.
(4) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2002, 124,
11566.
(5) See for example: (a) Burgess, K.; Ohlmeyer, M. J. J. Org. Chem. 1988,
53, 5178. (b) Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc. 1989,
111, 3426. (c) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem.
Soc. 1992, 114, 6671. (d) Togni, A.; Breutel, C.; Schnyder, A.; Spindler,
F.; Landert, H.; Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062. (e)
Fernandez, E.; Maeda, K.; Hooper, M. W.; Brown, J. M. Chem.sEur. J.
2000, 6, 1840. (f) Demay, S.; Volant, F.; Knochel, P. Angew. Chem., Int.
Ed. 2001, 40, 1235. (g) Perez Luna, A.; Ceschi, M. A.; Bonin, M.;
Micouin, L.; Husson, H.-P. J. Org. Chem. 2002, 67, 3522.
(6) For examples on noncatalytic hydroboration of cyclopropenes, see: (a)
Koster, R.; Arora, S.; Binger, P. Angew. Chem., Int. Ed. Engl. 1969, 8,
205. (b) Zimmerman, H. E.; Nuss, J. M.; Tantillo, A. W. J. Org. Chem.
1988, 53, 3792. (c) Rubin, M. A.; Baird, M. S.; Bolesov, I. G. Zh. Org.
Khim. 1997, 33, 966.
(7) For use of PBH in the Rh-catalyzed hydroboration of alkenes, see: Pereira,
S.; Srebnik, M. J. Am. Chem. Soc. 1996, 118, 909.
(8) No background reaction of 1a with PBH was observed in the absence of
Rh-catalyst. For noncatalytic hydroboration of acetylenes and alkenes with
PBH, see: Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992,
57, 3482.
Acknowledgment. The support of the National Science Foun-
dation (CHE-0096889) is gratefully acknowledged. M. Rubina
thanks UIC for the Graduate Fellowship.
(9) For the complete table on ligand effect, see Supporting Information.
(10) (a) Muller, P.; Pautex, N.; Doyle, M. P.; Bagheri, V. HelV. Chim. Acta
1990, 73, 1233. (b) Muller, P.; Granicher, C. HelV. Chim. Acta 1993, 76,
521.
(11) Boronic esters 3 were quantitatively converted into the corresponding acids
under mild conditions. See: Falck, J. R.; Bondlela, M.; Venkataraman,
S. K.; Srinivas, D. J. Org. Chem. 2001, 66, 7148.
Supporting Information Available: Experimental details (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
(12) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.
(13) Conditions: Pd(t-Bu3P)2 10 mol %, CsF (for cis-4b) or NaOH aq (for
cis-4f) 3 equiv, benzene, 80 °C.
References
(1) For application of cyclopropyl boronates in the Suzuki cross-coupling
reaction, see for example: (a) Zhou, S.-M.; Deng, M.-Z.; Xia, L.-J.; Tang,
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J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003 7199