C O M M U N I C A T I O N S
Table 2. Palladium-Catalyzed Cyclization of 1 Forming 2a
Scheme 3. Cyclization/Fragmentation of Allylborane Intermediates
a L and S Stand for large and small substituents, respectively.
a mixture of trans-2c and cis-2c (2:1) in 50% combined isolated
yield.14
Acknowledgment. Financial support from the Ministry of
Education, Culture, Sports, Science and Technology, Japanese
Government [Grant-in-Aid for Scientific Research (B) 16350058
and Priority Areas 17035065 and 18037059] is gratefully acknowl-
edged.
Supporting Information Available: Experimental details. This
References
a Conditions: 1 (1 mmol), Pd(acac)2 (10 mol %), n-Bu3P (20 mol %),
Et3B (300 mol %, 1 M in hexane) in THF (5 mL) at 50 °C under N2. b Trans
to cis ratio regarding hydroxy and vinyl substituents. c 1,2-trans, 1,4-trans:
1,2-cis, 1,4-trans:1,2-trans,1,4-cis:1,2-cis, 1,4-cis. d In addition to 2b, R,R-
diphenylacetaldehyde was obtained in 5% (run 1) and 52% yield (run 2).
(1) (a) Tsuji, J. Palladium-Catalyzed Nucleophilic Substitution Involving
Allylpalladium, Propargylpalladium, and Related Derivatives in Handbook
Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.;
Wiley-Interscience: New York, 2002; Vol. 2, p 1669. (b) Tsuji, J.
Transition Metal Reagents and Catalysts; John Wiley & Sons: Chichester,
2000; Chapter 4.
(2) Tamaru, Y. Palladium-Catalyzed Reactions of Allyl and Related Deriva-
tives with Organoelectrophiles. In Handbook of Organopalladium Chem-
istry for Organic Synthesis; Negishi, E.-i., Ed.; Wiley-Interscience: New
York, 2002; Vol. 2, p 1917.
selectively, being trans with respect to OH and the vinyl group.
Although the reason is not clear at the moment, the reaction of 1k
is one exception, which provides cis-2k exclusively. Interestingly,
the product cis-2k readily underwent the retro-ene reaction to
cleanly provide 5 with t1/2 ) ∼30 h at room temperature (CDCl3).
For aldehydes bearing different substituents (L: large, S: small)
on the R-carbon, hydroxy and L groups are placed trans to each
other in high preference: e.g. >30:1 for L ) Ph, S ) Me (run 3),
18 ()14 + 4):6 ()5 + 1) for L ) Ph, S ) Et (run 4).
Based on the isomerization from cis-2 to trans-2 (e.g. runs 1
and 2, Table 1, with the exception of run 9, Table 2) and high
preference of OH to be aligned with small substituents (S), the
most likely reaction mechanism is proposed in Scheme 3. Allylbo-
rane12 would form 8-membered-ring intermediates III and IV,
which have anti conformation with respect to L and CdO and hence
are responsible for the formation of cis-2‚BEt2 and trans-2‚BEt2,
respectively, both OBEt2 and S being cis.13 Formation of R,R-
diphenylacetaldehyde in as much as 52% yield during long heating
at 50 °C (footnote d in runs 1 and 2, Table 2) suggests that
fragmentation through an intermediate V might be accompanied
as a serious side reaction that renders the yields of 2 within a range
of good to modest.
(3) Mukai, R.; Horino, Y.; Tanaka, S.; Tamaru, Y.; Kimura, M. J. Am. Chem.
Soc. 2004, 126, 11138.
(4) Kimura, M.; Horino, Y.; Mukai, R.; Tanaka, S.; Tamaru, Y. J. Am. Chem.
Soc. 2001, 123, 10401.
(5) Umpolung of allyl alcohols and vinyl epoxides: (a) Olsson, V. J.; Sebelius,
S.; Selander, N.; Szabo´, K. J. J. Am. Chem. Soc. 2006, 128, 4588. (b)
Shimizu, M.; Kimura, M.; Tamaru, Y. Chem. Eur. J. 2005, 11, 6629. (c)
Zhu, S.-F.; Yang, Y.; Liu, B.; Zhou, Q.-L. Org. Lett. 2005, 7, 2333. (d)
Kimura, M.; Shimizu, M.; Tanaka, S.; Tamaru, Y. Tetrahedron 2005, 61,
3709. (e) Kimura, M.; Shimizu, M.; Shibata, K.; Tazoe, M.; Tamaru, Y.
Angew. Chem. Int. Ed. 2003, 42, 3392. (f) Araki, S.; Kameda, K.; Tanaka,
J.; Hirashita, T.; Yamamura, H.; Kawai, M. J. Org. Chem. 2001, 66, 7919.
(6) (a) Trost, B. M.; Xie, J. J. Am. Chem. Soc. 2006, 128, 6044. (b) Nishimura,
T.; Uemura, S. Synlett 2004, 201. (c) Nemoto, H.; Takahashi, E.; Ihara,
M. Org. Lett. 1999, 1, 517.
(7) Palladium-catalyzed cyclobutenol synthesis via C2-C3 bond formation:
Salem, B.; Suffert, J. Angew. Chem., Int. Ed. 2004, 43, 2826.
(8) (a) Tsuda, T.; Tokai, M.; Ishida, T.; Saegusa, T. J. Org. Chem. 1986, 51,
5216. (b) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981, 103,
5969. With ketones8b and ester enolates: (c) Elliott, M. R.; Dhimane,
A.-L.; Malacria, M. Tetrahedron Lett. 1998, 39, 8849.
(9) DMSO is recommended as the solvent. For example, the reaction of
R-phenylpropionaldehyde and isoprene oxide provides 1c′ (70%) selec-
tively in DMSO for 5 h at rt. Other common solvents provide mixtures
of products: 1c′ (30%), 3c′ (31%), 6 (17%) in acetonitrile for 3 h; 1c′
(20%), 3c′ (21%), 6 (17%) in THF for 22 h; 1c′ (12%), 3c′ (42%), 6
(20%) in CH2Cl2 for 20 h.
One-pot sequential amphiphilic allylation with vinyl epoxide can
be achieved (eq 2);
(10) Suzuki, S.; Fujita, Y.; Kobayashi, Y.; Sato, F. Tetrahedron Lett. 1986,
27, 69.
(11) R-Allylation of cyclohexanone silyl enol ether with vinyl epoxide without
details: Tsuji, J. Pure Appl. Chem. 1986, 56, 869.
(12) Allylborane may be generated by oxidative addition of Pd(0) upon the
allylic C-O bond of 1, followed by transmetallation of the π-allylpalla-
dium thus formed with Et3B.
(13) Although the equilibrium between III and cis-2‚BEt2 may be speculative,
it would be feasible due to the ring strain and cis orientation of the
substituents. Note the ready retro-ene reaction of 2k to 5 at rt.
(14) In DMSO (2.5 mL), under otherwise identical conditions, the first allylation
proceeded smoothly (2 h, rt), but the second allylation was very slow and
required heating at 50°C for 84 h, yielding trans-2c (31%) as a single
isomer.
a solution of R-phenylpropionaldehyde, vinyl epoxide (1.2 equiv),
Pd(acac)2 (0.1 equiv), and n-Bu3P (0.2 equiv) in THF was stirred
at room temperature for 3 h under N2. Then, Et3B (3 equiv, 1 M in
THF) was added into the mixture, and the solution was stirred for
84 h at room temperature. Usual workup and purification provided
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