Communications
Challenges and Solutions for Organic Synthesis (Eds.: J. Chris-
toffers, A. Baro), Wiley-VCH, Weinheim, 2005; b) J. Christoff-
ers, A. Baro, Adv. Synth. Catal. 2005, 347, 1473 – 1482; c) C. J.
Douglas, L. E. Overman, Proc. Natl. Acad. Sci. USA 2004, 101,
5363 – 5367; d) T. Denissova, L. Barriault, Tetrahedron 2003, 59,
10105 – 10146; e) J. Christoffers, A. Mann, Angew. Chem. 2001,
113, 4725 – 4732; Angew. Chem. Int. Ed. 2001, 40, 4591 – 4597;
f) E. J. Corey, A. Guzman-Perez, Angew. Chem. 1998, 110, 402 –
415; Angew. Chem. Int. Ed. 1998, 37, 388 – 401; g) K. Fuji, Chem.
Rev. 1993, 93, 2037 – 2066.
Table 1: Substrate scope in the pinacol rearrangement to install angular
stereogenic centers.[a,b]
Entry R[c]
Yield [%] T [8C] t [h] Yield [%]
ee [%]
(step 1)
89 (4b)
94 (4c)
(step 2)
92 (5b)
90 (5c)
1
2
0
0
1
3
98
98
[4] For a rearrangement-based approach to quaternary stereocen-
ters and its application in natural-products synthesis, see: a) M.
Shimazaki, H. Hara, K. Suzuki, G. Tsuchihashi, Tetrahedron
Lett. 1987, 28, 5891 – 5894; b) K. Suzuki, Yuki Gosei Kagaku
Kyokaishi 1988, 46, 365 – 377; c) T. Nagasawa, K. Taya, M.
Kitamura, K. Suzuki, J. Am. Chem. Soc. 1996, 118, 8949 – 8950;
d) T. Saito, T. Suzuki, C. Akiyama, T. Ochiai, K. Takeuchi, T.
Matsumoto, K. Suzuki, J. Am. Chem. Soc. 1998, 120, 11633 –
11644.
[5] a) J. W. Bode, Y. Hachisu, T. Matsuura, K. Suzuki, Tetrahedron
Lett. 2003, 44, 3555 – 3558; b) J. W. Bode, K. Suzuki, Tetrahedron
Lett. 2003, 44, 3559 – 3563; c) T. Matsuura, J. W. Bode, Y.
Hachisu, K. Suzuki, Synlett 2003, 1746 – 1748.
3
87 (4d)
0
1.5
96 (5d)
98
4
5
90 (4e)
98 (4 f)
0
2
9
95 (5e)
98
71
25
86[d] (5 f)
6
– (4g)
0
5
82[d,e] (5 f) 96
ꢀ
ꢀ
[a] Step 1: R groups were installed by adding R Li or R MgX (2.5–
3.0 equiv) to (R)-3 (98% ee). [b] Step 2: Unless otherwise noted, the
reaction was performed with BF3·OEt2 (20 mol%) in CH2Cl2 at the
temperature indicated. [c] The dot represents the position of connectiv-
ity. [d] A stoichiometric amount of BF3·OEt2 was used. [e] Overall yield for
3 steps: complexation, rearrangement, and decomplexation; see the
Supporting Information.
[6] a) Y. Hachisu, J. W. Bode, K. Suzuki, J. Am. Chem. Soc. 2003,
125, 8432 – 8433; b) Y. Hachisu, J. W. Bode, K. Suzuki, Adv.
Synth. Catal. 2004, 346, 1097 – 1100; c) H. Takikawa, Y. Hachisu,
J. W. Bode, K. Suzuki, Angew. Chem. Int. Ed. 2006, 118, 3572 –
3574; Angew. Chem. Int. Ed. 2006, 45, 3492 – 3494.
ee value was noted, the angularly alkynylated product 5 f
(96% ee) was obtained in high yield (82% over three steps)
by the facile 1,2-shift of the complexed alkynyl group
followed by decomplexation.
The excellent migratory behavior of an allyl group
(Table 1, entry 4) encouraged us to exploit this process in
the context of the synthesis of isoprenoid-containing natural
products, such as 1. Pleasingly, a prenyl group could be
introduced stereo- and regioselectively at the angular position
by the treatment of (R)-3 with a prenylbarium reagent[18]
followed by the BF3·OEt2-catalyzed rearrangement
(Scheme 6).
[7] H. Muxfeldt, G. Haas, G. Hardtmann, F. Kathawala, J. B.
Mooberry, E. J. Vedejs, J. Am. Chem. Soc. 1979, 101, 689 – 701.
[8] The ee values were determined by HPLC analysis with a
Chiralpak AD-H column (see Supporting Information).
[9] The following chemical yields were recorded when other (Lewis)
acids were used: Et2AlCl: 76%, TiCl4: 75%, Sc(OTf)3: 91%,
trifluoroacetic acid (TFA): 77%, triflic acid (TfOH): 92%.
[10] The S absolute configuration of ketone 5a was determined by
single-crystal X-ray analysis of the (S)-camphanate derivative,
which was obtained by the reduction of 5a (NaBH4, THF,
MeOH, 08C) to give the cis diol as a single product followed by
esterification of the secondary alcohol with (S)-camphanic
chloride (DMAP, CH2Cl2, 08C) (see Supporting Information).
[11] K. Nakamura, Y. Osamura, J. Am. Chem. Soc. 1993, 115, 9112 –
9120, and references therein.
[12] The remarkably high selectivity for the formation of the cis diol
from 3 hampered our efforts to obtain a sample of the trans diol
6 for this comparative experiment. A small sample of 6 was
isolated by column chromatography, preparative TLC, and
recycling HPLC from a mixture rich in the cis diol (4a/6 30:1)
that was obtained from the reaction of 3 with a vinyl Grignard
reagent (see Supporting Information).
[13] a) M. B. Smith, J. March in Marchꢀs Advanced Organic Chemis-
try, 5th ed., Wiley, New York, 2001, p. 435, and references
therein; b) N. Isaacs, Physical Organic Chemistry, 2nd ed.,
Longman Scientific Technical, England, 1995, p. 454.
Scheme 6. Selective installation of a prenyl group.
Received: December 20, 2006
Published online: March 27, 2007
[14] a) K. Suzuki, E. Katayama, G. Tsuchihashi, Tetrahedron Lett.
1983, 24, 4997 – 5000; b) K. Suzuki, E. Katayama, G. Tsuchiha-
shi, Tetrahedron Lett. 1984, 25, 1817 – 1820.
[15] a) T. Shinohara, K. Suzuki, Synthesis 2003, 141 – 146; b) T.
Shinohara, K. Suzuki, Tetrahedron Lett. 2002, 43, 6937 – 6940.
[16] a) P. A. Wender, D. A. Holt, S. M. Sieburth, J. Am. Chem. Soc.
1983, 105, 3348 – 3350; b) K. Suzuki, T. Ohkuma, M. Miyazawa,
G. Tsuchihashi, Tetrahedron Lett. 1986, 27, 373 – 376; c) F. J.
Schoenen, J. A. Porco, Jr., S. L. Schreiber, G. D. VanDuyne, J.
Clardy, Tetrahedron Lett. 1989, 30, 3765 – 3768.
ꢀ
Keywords: asymmetric synthesis · C C coupling · nucleophilic
addition · quaternary carbon centers · rearrangement
.
[1] a) H. Shigemori, K. Komatsu, Y. Mikami, J. Kobayashi, Tetrahe-
dron 1999, 55, 14925 – 14930; b) K. Komatsu, H. Shigemori, M.
Shiro, J. Kobayashi, Tetrahedron 2000, 56, 8841 – 8844.
[2] a) H. Kushida, S. Nakajima, T. Koyama, H. Suzuki, K. Ojiri, H.
Suda, JP 08143569, 1996; b) A. M. Socha, D. Garcia, R. Sheffer,
D. C. Rowley, J. Nat. Prod. 2006, 69, 1070 – 1073.
[17] See references [4c] and [4d].
[18] A. Yanagisawa, S. Habaue, K. Yasue, H. Yamamoto, J. Am.
Chem. Soc. 1994, 116, 6130 – 6141.
[3] For recent reviews on the stereoselective construction of
quaternary stereocenters, see: a) Quaternary Stereocenters:
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 3252 –3254