pubs.acs.org/Organometallics Published on Web 12/28/2009 r 2009 American Chemical Society 378 Organometallics 2010, 29, 378–388 DOI: 10.1021/om900800z Platinum-Catalyzed Asymmetric Alkylation of Bis(isitylphosphino)ethane: Stereoselectivity Reversal in Successive Formation of Two P-C Bonds Timothy W. Chapp, † David S. Glueck,* ,† James A. Golen, ‡ Curtis E. Moore, ‡ and Arnold L. Rheingold ‡ † 6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755 and ‡ Department of Chemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 Received September 14, 2009 Alkylation of the bis(secondary) phosphine IsHP(CH 2 ) 2 PHIs (1; Is = isityl = 2,4,6-(i-Pr) 3 C 6 H 2 ) with 2-(bromomethyl)naphthalene using 10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)- (Ph)(Cl) and the base NaOSiMe 3 selectively yielded meso-IsP(CH 2 Ar)(CH 2 ) 2 P(CH 2 Ar)(Is) (2; Ar = 2-naphthyl; dr = meso/rac ratio = 3.4:1). Half-alkylated IsP(CH 2 Ar)(CH 2 ) 2 PH(Is) (3), an inter- mediate in this reaction, was prepared from 1 by deprotonation (s-BuLi) and alkylation with 2-(chloromethyl)naphthalene. Analysis of the observed diastereo- and enantioselectivity in the Pt-catalyzed alkylations of 1 and 3 yielded quantitative information on the stereoselectivity of both P-C bond-forming steps. The first alkylation (1 f 3) resulted in diastereoselective formation of a tertiary phosphine stereocenter (∼2:1 ratio). In the second alkylation (3 f 2), however, both (R P )-3 and (S P )-3 (the label refers to the configuration of the tertiary phosphine) selectively formed meso-2, instead of (R,R)-2 or (S,S)-2, respectively (the ratios were ca. 3:1 and 7:1). Thus, the tertiary phosphine in 3 favored alternation of stereochemistry in the alkylation of the secondary phosphine (substrate control with negative cooperativity). Platinum-catalyzed alkylation of IsPH(CH 2 ) 2 OSi(i- Pr) 3 (6) gave IsP(CH 2 Ar)(CH 2 ) 2 OSi(i-Pr) 3 (9) in a 1.5:1 enantiomeric ratio (er). A related reaction of IsPH(CH 2 ) 2 OSiMe 3 (4) gave a mixture of IsP(CH 2 Ar)(CH 2 ) 2 OR (R = SiMe 3 (7); R = H (8)), while alkylation of IsPH(CH 2 ) 2 OH (5) gave 8 in about 2:1 er. Thus, the nature, and even the absolute configuration, of the pendant group X three bonds from the reactive phosphorus center in the substrates IsHP(CH 2 ) 2 X (X = PHIs (1), P(CH 2 Ar)(Is) (3), OSiMe 3 (4), OH (5), OSi(i-Pr) 3 (6)) had a strong influence on the selectivity of Pt-catalyzed phosphorus alkylation. Possible mechanistic explanations for this substrate control are discussed. Introduction Bifunctional symmetrical substrates with two equivalent reactive sites present special problems and opportunities in asymmetric catalysis. After the catalyst mediates formation of one chiral center, the selectivity of the second reaction may be the same (catalyst control) or different (substrate con- trol). 1 Catalyst control may result in asymmetric amplifica- tion and high enantiomeric ratio (er) for the rac product. Substrate control may reinforce the selectivity of the catalyst (positive cooperativity) or compete with it (negative coop- erativity). 2 These effects depend on the length of the linker between the reactive sites, as shown spectacularly in Ru- (Binap)-catalyzed hydrogenation of diketones (Scheme 1). Catalyst control in reduction of A led to high diastereoselec- tivity, and the favored rac product was formed in high ee. While hydrogenation of B also gave the rac diol enantio- selectively, the major product was meso, presumably as a result of substrate control. 3 Understanding the structural basis for such effects is poten- tially useful in designing substrates for asymmetric catalysis. 4 *To whom correspondence should be addressed. E-mail: Glueck@ Dartmouth.Edu. (1) Lagasse, F.; Tsukamoto, M.; Welch, C. J.; Kagan, H. B. J. Am. Chem. Soc. 2003, 125, 7490–7491. (2) (a) Takahata, H.; Takahashi, S.; Kouno, S.; Momose, T. J. Org. Chem. 1998, 63, 2224–2231. (b) El Baba, S.; Sartor, K.; Poulin, J.-C.; Kagan, H. B. Bull. Soc. Chim. Fr. 1994, 131, 525–533. (c) Rautenstrauch, V. Bull. Soc. Chim. Fr. 1994, 131, 515–524. (d) Tai, A.; Ito, K.; Harada, T. Bull. Chem. Soc. Jpn. 1981, 54, 223–227. (e) Muramatsu, H.; Kawano, H.; Ishii, Y.; Saburi, M.; Uchida, Y. J. Chem. Soc., Chem. Commun. 1989, 769–770. (f) Aggarwal, V. K.; Evans, G.; Moya, E.; Dowden, J. J. Org. Chem. 1992, 57, 6390–6391. (g) Hoye, T. R.; Mayer, M. J.; Vos, T. J.; Ye, Z. J. Org. Chem. 1998, 63, 8554–8557. (h) Kuwano, R.; Sawamura, M.; Shirai, J.; Takahashi, M.; Ito, Y. Tetrahedron Lett. 1995, 36, 5239–5242. (i) Hayashi, T.; Hayashizaki, K.; Ito, Y. Tetrahedron Lett. 1989, 30, 215–218. (j) Kalck, P.; Urrutigoïty, M. Coord. Chem. Rev. 2004, 248, 2193–2200. (k) Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew. Chem., Int. Ed. 1985, 24, 1–30. (3) Kitamura, M.; Ohkuma, T.; Inoue, S.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J. Am. Chem. Soc. 1988, 110, 629–631. (4) (a) Glueck, D. S. Dalton Trans. 2008, 5276–5286. (b) Glueck, D. S. Chem. Eur. J. 2008, 14, 7108–7117. (c) Glueck, D. S. Coord. Chem. Rev. 2008, 252, 2171–2179. (d) Glueck, D. S. Synlett 2007, 2627–2634.