A R T I C L E S
Tolstoy et al.
enantioselectivities, but is currently limited in its substrate scope.10
The synthesis of unfunctionalized, optically active gem-diarylal-
kanes is especially demanding. Few reports have been published
in this area,11 and these generally yield rather low ee values. Only
recently has a highly enantioselective route been reported; Carreira
et al. performed the Rh-catalyzed decarbonylation of optically pure
aldehydes to chiral diarylethanes.12 New, highly selective methods
to diarylmethine stereocenters are therefore still desired.
Table 1. Screening of Ir Catalysts in the Asymmetric
Hydrogenation of 1,1-Diaryl-Substituted Olefins 1 and 2a
The asymmetric hydrogenation of olefins is among the most
powerful methods in asymmetric synthesis.13 Since Pfaltz et
al.14 reported the first chiral mimic of Crabtree’s hydrogenation
catalyst,15 many groups have contributed to the development
of new N,P-ligated iridium catalysts,16,17 and recent work has
focused on expanding their substrate scope.18,19 We reasoned
that applying Ir-catalyzed asymmetric hydrogenation to form
diarylmethine stereogenic centers would expand the available
(10) Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed.
2007, 46, 6488–6491.
(11) (a) Wilkinson, J. A.; Rossington, S. B.; Ducki, S.; Leonard, J.; Hussain,
N. Tetrahedron 2006, 62, 1833–1844. (b) Okamoto, K.; Nishibayashi,
Y.; Uemura, S.; Toshimitsu, A. Angew. Chem., Int. Ed. 2005, 44,
3588–3591. (c) Wilkinson, J. A.; Rossington, S. B.; Ducki, S.; Leonard,
J.; Hussain, N. Tetrahedron: Asymmetry 2004, 15, 3011–3013. (d)
Prat, L.; Dupas, G.; Duflos, J.; Que´guiner, J.; Bourguignon, J.;
Levacher, V. Tetrahedron Lett. 2001, 42, 4515–4518. (e) Hatanaka,
Y.; Hiyama, T. J. Am. Chem. Soc. 1990, 112, 7793–7794.
(12) Fessard, T. C.; Andrews, S. P.; Motoyoshi, H.; Carreira, E. M. Angew.
Chem., Int. Ed. 2007, 46, 9331–9334.
(13) (a) Church, T. L.; Andersson, P. G. Coord. Chem. ReV. 2008, 252,
513–531. (b) Roseblade, S. J.; Pfaltz, A. C. R. Chim. 2007, 10, 178–
187. (c) Roseblade, S. J.; Pfaltz, A. Acc. Chem. Res. 2007, 40, 1402–
1411. (d) Ka¨llstro¨m, K.; Munslow, I.; Andersson, P. G. Chem.sEur.
J. 2006, 12, 3194–3200. (e) Cui, X.; Burgess, K. Chem. ReV. 2005,
105, 3272–3296.
(14) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998,
37, 2897–2899.
(15) Crabtree, R. H. Acc. Chem. Res. 1979, 12, 331–337.
(16) (a) Schrems, M. G.; Neumann, E.; Pfaltz, A. Heterocycles 2008, 76,
771–781. (b) Zhou, J.; Ogle, J. W.; Fan, Y.; Banphavichit(Bee), V.;
Zhu, Y.; Burgess, K. Chem.sEur. J. 2007, 13, 7162–7170. (c)
Cheemala, M. N.; Knochel, P. Org. Lett. 2007, 9, 3089–3092. (d)
Wang, C. J.; Sun, X.; Zhang, X. Angew. Chem., Int. Ed. 2005, 44,
4933–4935. (e) Bunlaksananusorn, T.; Polburn, K.; Knochel, P. Angew.
Chem., Int. Ed. 2003, 42, 3941–3943. (f) Tang, W.; Wang, W.; Zhang,
X. Angew. Chem., Int. Ed. 2003, 42, 943–946. (g) Perry, M. C.; Cui,
X.; Powell, M.; Hou, D.; Reibenspies, J.; Burgess, K. J. Am. Chem.
Soc. 2003, 125, 113–123. (h) Cozzi, P. G.; Menges, F.; Kaiser, S.
Synlett 2003, 6, 833–836. (i) Hou, D. R.; Reibenspies, J.; Colacot,
T. J.; Burgess, K. Chem.sEur. J. 2001, 7, 5391–5400. (j) Blankenstein,
J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001, 40, 4445–4447. (k) Cozzi,
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a Reaction conditions: 25 mg of 1 or 2, 1 mol % catalyst, 1 mL of
CH2Cl2. Hydrogenation of 1: 40 °C, 100 bar of H2, 24 h. Hydrogenation
of 2: 25 °C, 50 bar of H2, 24 h. b Conversion to alkane determined by
1H NMR spectroscopy. c Determined by chiral HPLC. For details see
Supporting Information. d Isolated yield.
methods for their synthesis. At first glance, this task appeared
difficult; two aryl groups often have very similar steric and
electronic properties. When reducing olefins bearing almost
identical groups at the prochiral carbon, we must rely on other
steric interactions to induce selectivity. Here, we describe a
method of making diarylmethine chiral centers from substrates
whose geminal olefin substituents differ very little. In one example,
these differ by only a single atom in the para-position. These results
support the hypothesis that steric hindrance in one specific quadrant
is playing a key role in directing the transformation.13a,17f,i,25
(17) (a) Die´guez, M.; Mazuela, J.; Pa`mies, O.; Verendel, J.; Andersson,
P. G. J. Am. Chem. Soc. 2008, 130, 7208–7209. (b) Die´guez, M.;
Mazuela, J.; Pa`mies, O.; Verendel, J.; Andersson, P. G. Chem.
Commun. 2008, 3888–3890. (c) Kaukoranta, P.; Engman, M.; Hedberg,
C.; Bergquist, J.; Andersson, P. G. AdV. Synth. Catal. 2008, 350, 1168–
1176. (d) Cheruku, P.; Paptchikhine, A.; Ali, M.; Neudo¨rfl, J.-M.;
Andersson, P. G. Org. Biomol. Chem. 2008, 6, 366–373. (e) Verendel,
J. J.; Andersson, P. G. Dalton Trans. 2007, 47, 5603–5610. (f)
Hedberg, C.; Ka¨llstro¨m, K.; Brandt, P.; Hansen, L. K.; Andersson,
P. G. J. Am. Chem. Soc. 2006, 128, 2995–3001. (g) Trifonova, A.;
Diesen, J. S.; Andersson, P. G. Chem.sEur. J. 2006, 12, 2318–2328.
(h) Trifonova, A.; Diesen, J. S.; Chapman, C. J.; Andersson, P. G.
Org. Lett. 2004, 6, 3825–3827. (i) Ka¨llstro¨m, K.; Hedberg, C.; Brandt,
P.; Bayer, A.; Andersson, P. G. J. Am. Chem. Soc. 2004, 126, 14308–
14309.
Results and Discussion
Substrate Synthesis. The present technique for producing
diarylmethine stereocenters, like most methods for their syn-
thesis, relies on the efficient synthesis of olefins in isomerically
pure form. Most of the olefins discussed in this paper can easily
be purified by recrystallization or chromatography, and many
of them are synthesized according to literature procedures, which
accentuates the usefulness of this method. Substrates (Z)-1, (Z)-
10 and (Z)-11 (Tables 1 and 4) were synthesized using the Heck
arylation of (E)-methyl cinnamate and isolated via standard flash
(18) (a) Cheruku, P.; Church, T. L.; Trifonova, A.; Wartmann, T.;
Andersson, P. G. Tetrahedron Lett. 2008, 49, 7290–7293. (b) Cheruku,
P.; Diesen, J. S.; Andersson, P. G. J. Am. Chem. Soc. 2008, 130, 5595–
5599. (c) Cheruku, P.; Gohil, S.; Andersson, P. G. Org. Lett. 2007, 9,
1659–1661. (d) Engman, M.; Diesen, J. S.; Paptchikhine, A.; Ander-
sson, P. G. J. Am. Chem. Soc. 2007, 129, 4536–4537. (e) Ka¨llstro¨m,
K.; Munslow, I.; Hedberg, C.; Andersson, P. G. AdV. Synth. Catal.
2006, 348, 2575–2578.
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