Job/Unit: O42941
/KAP1
Date: 10-09-14 19:26:20
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First Enantioselective Catalytic Wittig Reaction
Candy, J.-M. Pons, O. Chuzel, C. Bressy, Angew. Chem. Int.
of sterically more demanding derivative 11b did not lead to
an improvement (Table 1, entries 17 and 18). Conversion of
Ed. 2014, 53, 766–770; Angew. Chem. 2014, 126, 785–789.
4] a) A. H. Hoveyda, R. R. Schrock, Organic Synthesis Set,
Wiley-VCH, Weinheim, Germany, 2008, p. 210–229; b) S.
Kress, S. Blechert, Chem. Soc. Rev. 2012, 41, 4389–4408; c) J.
Hartung, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 10183–
[
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in the presence of 1,2-bis[(2R,5R)-2,5-diisopropylphos-
pholano]ethane [12a, (R,R)-iPr-BPE] gave the desired prod-
uct in up to 42% yield with 28%ee (Table 1, entries 19 and
10185; d) R. Gawin, M. Pieczykolan, M. Mali n´ ska, K. Wo z´ -
20). (R,R)-Ph-BPE (12b) gave comparable results under
niak, K. Grela, Synlett 2013, 24, 1250–1254.
both reaction conditions (Table 1, entries 21 and 22). How-
ever, utilization of (R,R)-Me-BPE (12c) proved once again
the general feasibility of this method, which led to 2 in
moderate yields and ee values (Table 1, entries 23 and 24).
[
[
5] a) U. Eder, G. Sauer, R. Wiechert, Angew. Chem. Int. Ed. Engl.
1971, 10, 496–497; Angew. Chem. 1971, 83, 492–493; b) Z. G.
Hajos, D. R. Parrish, J. Org. Chem. 1974, 39, 1615–1621; c) B.
Bradshaw, J. Bonjoch, Synlett 2012, 23, 337–356.
6] a) T. Takeda, Modern Carbonyl Olefination, Wiley-VCH,
Weinheim, Germany, 2004; for recent examples, see: b) L. Jedi-
nak, L. Rush, M. Lee, D. Hesek, J. F. Fisher, B. Boggess, B. C.
Noll, S. Mobashery, J. Org. Chem. 2013, 78, 12224–12228; c)
K. M. Lum, V. J. Xavier, M. J. H. Ong, C. W. Johannes, K.-P.
Chan, Chem. Commun. 2013, 49, 11188–11190; d) G. W. Wong,
C. R. Landis, Angew. Chem. Int. Ed. 2013, 52, 1564–1567; An-
gew. Chem. 2013, 125, 1604–1607; e) K. J. Hale, L. Wang, Org.
Lett. 2014, 16, 2154–2157; f) Q. Sha, Y. Wei, ChemCatChem
Conclusions
In summary, we introduced the desymmetrization of pro-
chiral ketone 1 into optically active olefin 2 by an asymmet-
ric Wittig reaction under catalytic conditions. In the pres-
ence of catalytic amounts of chiral phosphine derivatives
the desired product was obtained in very good enantiomeric
excess up to 90% with yields up to 63%, which prove the
general feasibility of an enantioselective catalytic Wittig re-
action. Over 50 years after the discovery of the Wittig reac-
2014, 6, 131–134.
[
7] For reviews, see: a) T. Rein, O. Reiser, Acta Chem. Scand. 1996,
50, 369–379; b) K. Tanaka, K. Fuji, J. Synth. Org. Chem. Jpn.
1
998, 56, 521–531; c) T. Rein, T. Pedersen, Synthesis 2002, 579–
5
94; for examples, see: d) S. Sano, K. Yokoyama, R. Teranishi,
M. Shiro, Y. Nagao, Tetrahedron Lett. 2002, 43, 281–284; e) S.
Sano, R. Teranishi, F. Nakano, K. In, H. Takeshige, T. Ishii,
M. Shiro, Y. Nagao, Heterocycles 2003, 59, 793–804; f) S. Nak-
amura, T. Ogura, L. Wang, T. Toru, Tetrahedron Lett. 2004,
[
18]
tion by Georg Wittig and co-workers, this is, to the best
of our knowledge, the first example of a catalytic enantiose-
lective version of this reaction.
4
5, 2399–2402; g) D. Monguchi, Y. Ohta, T. Yoshiuchi, T. Wat-
Supporting Information (see footnote on the first page of this arti-
anabe, T. Furuta, K. Tanaka, K. Fuji, Tetrahedron 2007, 63,
12712–12719.
1
13
cle): Experimental details, copies of the H NMR and C NMR
spectra of all key intermediates 1, 3–5 and final product 2, as well
as chiral GC chromatograms.
[8] a) T. Kumamoto, K. Koga, Chem. Pharm. Bull. 1997, 45, 753–
755; b) M. Mizuno, K. Fujii, K. Tomioka, Angew. Chem. Int.
Ed. 1998, 37, 515–517; Angew. Chem. 1998, 110, 525–527.
[
9] a) H. J. Bestmann, J. Lienert, Angew. Chem. Int. Ed. Engl. 1969,
8, 763–764; Angew. Chem. 1969, 81, 751–752; b) H. J. Best-
mann, J. Lienert, Chem.-Ztg. 1970, 94, 487–488; c) B. M. Trost,
D. P. Curran, J. Am. Chem. Soc. 1980, 102, 5699–5700; d)
B. M. Trost, D. P. Curran, Tetrahedron Lett. 1981, 22, 4929–
Acknowledgments
Financial support from the Deutsche Forschungsgemeinschaft
(DFG) (WE 3605/3-1) and the Leibniz-Institut für Katalyse e.V. an
4932.
der Universtät Rostock, as well as support and advice from Dr. J.
Holz, Dr. K. Junge, Prof. A. Börner, and Prof. M. Beller are grate-
fully acknowledged.
[
10] a) C. J. O’Brien, J. L. Tellez, Z. S. Nixon, L. J. Kang, A. L. Car-
ter, S. R. Kunkel, K. C. Przeworski, G. A. Chass, Angew. Chem.
Int. Ed. 2009, 48, 6836–6839; Angew. Chem. 2009, 121, 6968–
6971; b) C. J. O’Brien, F. Lavigne, E. E. Coyle, A. J. Holohan,
B. J. Doonan, Chem. Eur. J. 2013, 19, 5854–5858; c) C. J.
O’Brien, Z. S. Nixon, A. J. Holohan, S. R. Kunkel, J. L. Tellez,
B. J. Doonan, E. E. Coyle, F. Lavigne, L. J. Kang, K. C.
Przeworski, Chem. Eur. J. 2013, 19, 15281–15289; d) I. J. Fair-
lamb, ChemSusChem 2009, 2, 1021–1024; e) S. P. Marsden,
Nat. Chem. 2009, 1, 685–687.
[
1] a) R. Noyori, Angew. Chem. Int. Ed. 2002, 41, 2008–2022; An-
gew. Chem. 2002, 114, 2108–2123; b) K. B. Sharpless, Angew.
Chem. Int. Ed. 2002, 41, 2024–2032; Angew. Chem. 2002, 114,
2
1
126–2135; c) W. S. Knowles, Angew. Chem. Int. Ed. 2002, 41,
998–2007; Angew. Chem. 2002, 114, 2096–2107.
[
2] a) P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 43,
[
11] a) S. P. Waters, Y. Tian, Y.-M. Li, S. J. Danishefsky, J. Am.
Chem. Soc. 2005, 127, 13514–13515; b) H. M. Lee, C. Nieto-
Oberhuber, M. D. Shair, J. Am. Chem. Soc. 2008, 130, 16864–
5
138–5175; Angew. Chem. 2004, 116, 5248–5286; b) J. Seayad,
B. List, Org. Biomol. Chem. 2005, 3, 719–724; c) M. J. Gaunt,
C. C. C. Johansson, A. McNally, N. T. Vo, Drug Discovery To-
day 2007, 12, 8–27; d) D. W. C. MacMillan, Nature 2008, 455,
1
6866; c) D. Minato, B. Li, D. Zhou, Y. Shigeta, N. Toyooka,
H. Sakurai, K. Sugimoto, H. Nemoto, Y. Matsuya, Tetrahedron
013, 69, 8019–8024.
3
04–308; e) A. Dondoni, A. Massi, Angew. Chem. Int. Ed.
2
2
008, 47, 4638–4660; Angew. Chem. 2008, 120, 4716–4739; f)
[
12] a) K. Kato, C. Matsuba, T. Kusakabe, H. Takayama, S. Yama-
mura, T. Mochida, H. Akita, T. y. A. Peganova, N. V. Vologdin,
O. V. Gusev, Tetrahedron 2006, 62, 9988–9999; b) T. Kanger,
K. Raudla, R. Aav, A.-M. Müürisepp, T. Pehk, M. Lopp, Syn-
thesis 2005, 3147–3151.
13] a) T. Werner, Adv. Synth. Catal. 2009, 351, 1469–1481; b) T.
Werner, A. M. Riahi, H. Schramm, Synthesis 2011, 3482; T.
Werner, A. M. Riahi, H. Schramm, Synthesis 2011, 3490.
S. Bertelsen, K. A. Jorgensen, Chem. Soc. Rev. 2009, 38, 2178–
2
189; g) A. Berkessel, H. Gröger, Asymmetric Organocatalysis,
Wiley-VCH, Weinheim, Germany, 2005; h) P. I. Dalko (Ed.),
Enantioselective Organocatalysis, Wiley-VCH, Weinheim, Ger-
many, 2007; i) M. T. Reetz, B. List, S. Jaroch, H. Weinmann,
Organocatalysis, Springer, Berlin, 2008.
[
[
3] a) R. W. Hoffmann, Angew. Chem. Int. Ed. 2003, 42, 1096–
1
109; Angew. Chem. 2003, 115, 1128–1142; b) A. Enriquez-
Garcia, E. P. Kundig, Chem. Soc. Rev. 2012, 41, 7803–7831; c)
N. R. Babij, J. P. Wolfe, Angew. Chem. Int. Ed. 2013, 52, 9247–
[14] T. Werner, M. Hoffmann, S. Deshmukh, Eur. J. Org. Chem.,
DOI: 10.1002/ejoc.201403113.
9
250; Angew. Chem. 2013, 125, 9417–9420; d) M. S. Manna, S.
[15] J. Buddrus, Angew. Chem. Int. Ed. Engl. 1968, 7, 536–537; An-
Mukherjee, Chem. Sci. 2014, 5, 1627–1633; e) C. Roux, M.
gew. Chem. 1968, 80, 535–536.
Eur. J. Org. Chem. 0000, 0–0
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