(2,3-O-Isopropylidene)-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane1

(R,R)

[32305-98-9]  · C31H32O2P2  · (2,3-O-Isopropylidene)-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane  · (MW 498.57) (S,S)

[37002-48-5]

(chiral bidentate phosphine, useful in asymmetric catalysis1)

Alternate Name: DIOP.

Physical Data: mp 88-89 °C; [a]20D -12.5° (c 4.6, C6H6).

Solubility: sol most usual organic solvents.

Form Supplied in: white solid; both enantiomers available.

Preparative Methods: can be prepared in four steps from diethyl tartrate.2 The two phosphorus groups are introduced in the last step of the reaction sequence using LiPPh2,2 KPPh2,3 or LiP(BH3)PPh2.4 DIOP has also been prepared from 1,2:3,4-diepoxybutane.5

Handling, Storage, and Precautions: air stable.

Introduction.

DIOP was the first example of a C2 chelating diphosphine for transition metal complexes to be used in asymmetric catalysis. It was also one of the first examples of a useful C2 chiral auxiliary.6 DIOP can be considered as an example of the first generation of chelating diphosphine ligands with a chiral carbon skeleton, which were followed over the next 20 years by many examples of chelating diphosphines, one of the most efficient of which is BINAP (2,2-Bis(diphenylphosphino)-1,1-binaphthyl).1d The ready availability of DIOP has stimulated research in asymmetric catalysis beyond the area of asymmetric hydrogenation.

Asymmetric Hydrogenation.

Conjugated acids (eq 1)2,7 or various a-N-acyldehydroamino acids (eq 2)2,8,9 are structural units which sometimes give quite high ee's in the presence of rhodium complexes formed in situ (such as Rh(Cl)(cod)(DIOP)) or isolated as cationic complexes, for example [Rh(cod)(DIOP)]+ PF6-. Hydrogenation of N-acetamidocinnamic acid using [Rh(DIOP)2]+ BF4- instead of [Rh(cod)(DIOP)]+ BF4- as catalyst (80 °C, 1 bar H2) gives a slower reaction but with a significant increase in the ee (94% ee instead of 82% ee).10

Enamides lacking a carboxy group on the double bond also act as excellent substrates in asymmetric hydrogenations, as exemplified in eq 3.11

Ketones are known to be quite unreactive in homogeneous hydrogenations catalyzed by rhodium complexes. However, catalytic amounts of a base enhance the reactivity. In this way, acetophenone is hydrogenated to 2-phenylethanol in 80% ee in the presence of [Rh(Cl)(cod)(DIOP)]/NEt312 or N(CH2OH)3.13 Aromatic a-amino ketones are reduced to the alcohols with high ee's. For example, 2-naphthyl-N,N-diethylaminoethanol is produced in 95% ee by hydrogenation of the corresponding ketone.13 Imines are very difficult to hydrogenate in the presence of rhodium catalysts, including [Rh(Cl)(cod)(DIOP)].1 However, it was recently discovered that iridium complexes with a chiral chelating diphosphine are selective catalysts for the hydrogenation of imines. DIOP gives the best result (63% ee) for the reduction of RN=C(Me)CH2OMe (R = 2,5-Me2C6H3).14

Asymmetric Hydrosilylation.

Hydrosilylation of ketones catalyzed by chiral metal complexes, followed by hydrolysis, produces enantiomerically enriched alcohols. Rhodium complexes with chiral chelating diphosphines have been used successfully. In this context, DIOP was one of the ligands investigated. Aryl alkyl ketones provide the corresponding alcohols in low ee with Ph2SiH2, but a-NpPhSiH2 gives ee's in the range of 50-60%.12 This silane is also excellent for hydrosilylation of i-butyl levulinate (84% ee) and n-propyl pyruvate (85% ee).15 Imines are transformed into amines (ee <= 65%) by Ph2SiH2 with a rhodium-DIOP catalyst.16

Asymmetric Hydroformylation.

DIOP was very useful in the early stages of investigation of asymmetric hydroformylation of alkenes in the presence of rhodium or palladium catalysts. The combination of PtCl2(diphosphine) and SnCl2, where the diphosphine is a DIOP derivative (DIPHOL, eq 4), is an excellent system, although requiring high pressures.17 In the case of the hydroformylation of styrene, the branched aldehyde is the major product. The various hydroformylations or hydroesterifications have been reviewed.1e Asymmetric hydroformylation of N-acylaminoacrylic acid esters is efficiently catalyzed by [Rh(CO)(PPh3)3] + DIOP, giving the branched aldehyde in 60% ee.18

Asymmetric Hydroboration.

Hydroborations of alkenes by catecholborane have been catalyzed by [Rh(Cl)(cod)(diphosphine)].19 For example, norbornene gives, after oxidation, exo-norborneol (82% ee) when a DIOP derivative (2-MeO-DIOP) was used (eq 5). Lower ee's were observed with DIOP, DIPAMP, and BINAP. The effectiveness of DIOP was also noticed in another report.20

Miscellaneous Reactions.

Hydrocyanation of norbornene is catalyzed by [Pd(DIOP)2], leading to exo-2-cyanonorbornane (16% ee), while [Pd(BINAP)2] gives 40% ee.21 An asymmetric rearrangement was catalyzed by a nickel(0) complex bearing a diphosphine ligand (eq 6).22 A DIOP derivative (MOD-DIOP) was more efficient than DIOP or BINAP. MOD-DIOP has previously been found to improve the enantioselectivity, with respect to DIOP, in rhodium-catalyzed hydrogenation of conjugated acids (ee's 90-95%).23 Structural modifications of DIOP are very easy to perform by changing the nature of the aromatic rings or the acetal group, allowing tuning of the enantioselectivity. Many publications describe modified DIOP derivatives. DIOP has been utilized in several stoichiometric reactions, for example in an intramolecular Wittig reaction for the synthesis of the bis-nor-Wieland-Miescher ketone (52% ee).24


1. (a) Kagan, H. B. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed; Pergamon: Oxford, 1982; Vol. 8, pp 464-498. (b) Kagan, H. B. In Asymmetric Synthesis; Morrison, J. D., Ed; Academic: New York, 1985; Vol. 5, pp 1-39. (c) Brunner, H. Top. Stereochem. 1988, 18, 129. (d) Takaya, H.; Ohta, T.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed; VCH: New York, 1993; pp 1-39. (e) Ojima, I.; Hirai, K. In Asymmetric Synthesis; Morrison, J. D., Ed; Academic: New York, 1985; Vol. 5, pp 103-146.
2. Kagan, H. B.; Dang, T. P. JACS 1972, 94, 6429.
3. Murrer, B. A.; Brown, J. M.; Chaloner, P. A.; Nicholson, P. N.; Parker, D. S 1979, 350.
4. Brisset, H.; Gourdel, Y.; Pellon, P.; Le Carre, M. TL 1993, 34, 4523.
5. Zhang, S. Q.; Zhang, S. Y.; Feng, R. TA 1991, 2, 173.
6. Whitesell, J. K. CRV 1989, 89, 1581.
7. Stoll, A. P.; Süess, R. HCA 1974, 57, 2487.
8. Gelbard, G.; Kagan, H. B.; Stern, R. T 1976, 32, 233.
9. Townsend, J. M.; Blount, J. F.; Sun, R. C.; Zawoiski, S.; Valentine, D., Jr. JOC 1980, 45, 2995.
10. James, B. R.; Mahajan, D. JOM 1985, 279, 31.
11. Sinou, D.; Kagan, H. B. JOM 1976, 114, 325.
12. Bakos, J.; Toth, I.; Heil, B.; Marko, L. JOM 1985, 279, 23.
13. Chan, A. S. C.; Landis, C. R. J. Mol. Catal. 1989, 49, 165.
14. Chan, Y. N. C.; Osborn, J. A. JACS 1990, 112, 9400.
15. Ojima, I.; Kogure, T.; Kumagai, M. JOC 1977, 42, 1671.
16. Kagan, H. B.; Langlois, N.; Dang, T. P. JOM 1975, 90, 353.
17. Consiglio, G.; Pino, P.; Flowers, L. I.; Pittman, C. U., Jr. CC 1983, 612.
18. Gladiali, S.; Pinna, L. TA 1991, 2, 623.
19. Burgess, K.; van der Donk, W. A.; Ohlmeyer, M. J. TA 1991, 2, 613.
20. Sato, M.; Miyaura, N.; Suzuki, A. TL 1990, 31, 231.
21. (a) Hodgson, M.; Parker, D.; Taylor, R. J.; Ferguson, G. OM 1988, 7, 1761. (b) Elmes, P. S.; Jackson, W. R. AJC 1982, 35, 2041.
22. Hiroi, K.; Arinaga, Y.; Ogino, T. CL 1992, 2329.
23. Morimoto, T.; Chiba, M.; Achiwa, K. TL 1989, 30, 735.
24. Trost, B. M.; Curran, D. P. TL 1981, 22, 4929.

Henri Kagan

Université de Paris-Sud, Orsay, France



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