2-(Diphenylphosphino)-N,N-dimethyl[1,1-binaphthalen]-2-amine1

[216368-93-3[,[233752-13-1]  · C34H28NP  · (MW 481.57)

(chiral ligand1)

Alternate Name: 2-(dimethylamino)-2-(diphenylphosphino)-1,1-binaphthyl; MAP.

Physical Data: (R)-(-) amorphous solid, [a]D -19.0 (c 1.0, THF).1 (S)-( + ) amorphous solid +26.6 (c 1.0, THF).2

Solubility: (R)-( + ) and (S)-(-) very well soluble in toluene, CH2Cl2, AcOEt, THF; well-soluble in ether; sparingly soluble in MeOH, EtOH, and hexane.

Preparative Methods: (R)-2-(diphenylphosphino)-N,N-dimeth-yl[1,1-binaphthalen]-2-amine (MAP) is conveniently prepared from the triflate of (R)-dimethyl-NOBIN by the Pd(0)-catalyzed coupling with Ph2P(O)H followed by reduction of the resulting phosphine oxide with Cl3SiH (1).1 Practically identical procedure has been reported for the synthesis of (S)-MAP.2 Direct coupling of the triflate with Ph2PH was unsuccessful,1 while the Ni(0)-catalyzed coupling with Ph2PCl is capricious, giving 0-40% of MAP.3

An analogous procedure, starting with NOBIN acetamide leads to desmethyl-MAP (2).1,4 A different approach to the same product relies on the Hofmann rearrangement of the corresponding amide (obtained by partial hydrolysis from the corresponding nitrile), followed by reduction of the P-O bond (3).5 Further analogues with various N,N-dialkyl and P,P-dialkyl/diaryl groups have also been described.1,6 Their synthesis utilizes either the triflate coupling (as in 1) (ref 1) or the lithiation of the corresponding bromide with t-BuLi followed by quenching with R2PCl.6

Drying: standard drying during the work up; not hygroscopic.

Handling, Storage, and Precautions: keep tightly closed, store in a cool dark place; deteriorates when exposed to direct sunshine and air.

The Pd(0)-complexes of (R)-MAP and its N,N-dialkyl analo-gues1 catalyze allylic substitution of allylic esters (acetates and carbonates; R = MeCO or MeOCO) with malonate nucleophiles (4) in up to 73% ee (R = Ph).1 Improved asymmetric induction (up to 91% ee) has been reported for H8-MAP (5,5,6,6,7,7,8,8-octahydro-MAP), H8-Xyl-MAP [with P(3,5-Me2C6H3) group in place of PPh2] (R = Ph, R = H),7 and for MAP with chiral substituents on the nitrogen (86% ee).8 MAP and H8-Xyl-MAP are also efficient ligands when NaN(CHO)2 is utilized as N-nucleoph-ile (5), giving up to 69% ee (note that 95% ee has been obtained in this case with BINAP as ligand).9 Strong memory effects are observed in the case of cyclic substrates.10

In allylic substitution and presumably in other reactions (vide supra), MAP acts as an P,Cipso-ligand rather than P,N-ligand, as evidenced by NMR and X-ray crystallography (6).10,11 Strong memory effects, observed in the case of allylic substitution of cyclic substrates, are associated with this unusual coordination.10

MAP and its analogues considerably accelerate the Hartwig- Buchwald amination of aromatic and heteroaromatic halides and triflates (7).1,6,11,12 Similar acceleration is observed for Suzuki- Miyaura coupling, which appears quite general, tolerating a number of functional groups (8).6,10 Further enhancement of the reaction rate is attained when the PPh2 group in MAP is replaced by the more Lewis-basic PCy2 group.6

Asymmetric induction is attained for selected Suzuki-Miyaura aryl-aryl couplings (9). In this case, more electron-rich MAP with PCy2 group exhibits higher enantioselectivities (up to 87% ee) than its PPh2 counterpart (75% ee).13

Pyridine amide, derived from (S)-desmethyl-MAP, induces high enantioselectivity in Cu-catalyzed conjugate addition of Et2Zn to enones (10).4

MAP-type ligands also catalyze asymmetric vinylation of ketone enolates (11) with 56% ee for MAP (PPh2) and 90% ee for its PCy2 analogue (96% ee at -20 °C).6d


1. Vyskocil, s.; Smrcina, M.; Hanus, V.; Polásek, M.; Kocovský, P., J. Org. Chem. 1998, 63, 7738.
2. Ding, K.; Wang, Y.; Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo, Y.; Mikami, K., Chemistry-Eur. J. 1999, 5, 1734.
3. Vyskocil, s.; Kocovský, P., unpublished results.
4. Hu, X.; Chen, H.; Zhang, X., Angew. Chem., Int. Ed. 1999, 38, 3518.
5. Sumi, K.; Ikariya, T.; Noyori, R., Can. J. Chem. 2000, 78, 697.
6. (a) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L., J. Am. Chem. Soc. 1999, 121, 4369. (b) Hu, X.; Chen, H.; Zhang, X., Angew. Chem., Int. Ed. 1999, 38, 3518. (c) Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L., J. Am. Chem. Soc. 2000, 122, 1360. (d) Chieffi, A.; Kamikawa, K.; Åhman, J.; Fox, J. M.; Buchwald, S. L., Org. Lett. 2001, 3, 1897.
7. Wang, Y.; Guo, H.; Ding, K., Tetrahedron: Asymmetry 2000, 11, 4153.
8. Wang, Y.; Li, X., Ding, K. L., Tetrahedron Lett. 2002, 43, 159.
9. Wang, Y.; Ding, K., J. Org. Chem. 2001, 66, 3238.
10. Lloyd-Jones, G. C.; Stephen, S. C.; Murray, M.; Butts, C. P.; Vyskocil, s.; Kocovský, P., Chem. Eur. J. 2000, 6, 4348.
11. Kocovský, P.; Vyskocil, s.; Císarová, I.; Sejbal, J.; Tislerová, I.; Smrcina, M.; Lloyd-Jones, G. C.; Stephen, S. C.; Butts, C. P.; Murray, M.; Langer, V., J. Am. Chem. Soc. 1999, 121, 7714.
12. Vyskocil, s.; Smrcina, M.; Kocovský, P., Tetrahedron Lett. 1998, 39, 9289.
13. Yin, J. J.; Buchwald, S. L., J. Am. Chem. Soc. 2000, 122, 12051.

Pavel Kocovský

University of Glasgow, UK



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