Dirhodium(II) Tetrakis(methyl 2-pyrrolidone-5(S)-carboxylate)

[131766-06-8]  · C24H36N4O12Rh2  · Dirhodium(II) Tetrakis(methyl 2-pyrrolidone-5(S)-carboxylate)  · (MW 778.46)

(highly enantioselective catalyst for carbenoid reactions of diazo compounds)1-3

Physical Data: l 615 nm, ε 211 (ClCH2CH2Cl). 1H NMR (CDCl3) of Rh2(5S-MEPY)4(MeCN)2: d 4.32 (dd, J = 8.8, 3.0 Hz, 2H), 3.95 (dd, J = 8.6, 2.1 Hz, 2H), 3.70 (s, 6H), 3.68 (s, 6H), 2.70-2.55 (m, 4H), 2.26 (s, 6H), 1.8-2.4 (m, 12H). [a]D23 = -259.5° (MeCN, c = 0.098).

Solubility: sol MeOH, MeCN, acetone; slightly sol CH2Cl2, ClCH2CH2Cl, toluene.

Form Supplied in: red crystals as the bis-acetonitrile complex; blue solid after removal of the axial nitrile ligands.

Preparative Method: from Dirhodium(II) Tetraacetate by ligand substitution with methyl 2-pyrrolidone-5(S)-carboxylate.4,5

Handling, Storage, and Precautions: air stable, weakly hygroscopic; stored in desiccator.


The preparation of the title reagent, Rh2(5S-MEPY)4, is the same as that used for Dirhodium(II) Tetraacetamide6 or Dirhodium(II) Tetra(caprolactam).7 Ligand exchange occurs in refluxing chlorobenzene, and the acetic acid that is liberated is trapped in a Soxhlet extraction apparatus by sodium carbonate. Purification occurs by chromatography on a CN-capped silica column; recrystallization from acetonitrile-2-propanol (1:1) provides Rh2(5S-MEPY)4(MeCN)2(i-PrOH). Four 2-pyrrolidone-5(S)-carboxylate molecules ligate one dirhodium(II) nucleus; each rhodium is bound to two nitrogen and two oxygen donor atoms arranged in a cis configuration.4 The methyl carboxylate substituents are positioned with a counterclockwise orientation on each rhodium face.

Metal Carbene Transformations.

The effectiveness of Rh2(5S-MEPY)4 and its 5R-form, Rh2(5R-MEPY)4, is exceptional for highly enantioselective intramolecular cyclopropanation8 and carbon-hydrogen insertion9 reactions. Intermolecular cyclopropanation occurs with lower enantiomeric excesses10 than with alternative chiral copper salicylaldimine11 or C2-symmetric semicorrin12 or bis-oxazoline13 copper catalysts, but intermolecular cyclopropenation exhibits higher enantiocontrol with Rh2(MEPY)4 catalysts.14 The methyl carboxylate attachment of Rh2(5S-MEPY)4 is far more effective than sterically similar benzyl or isopropyl attachments for enantioselective metal carbene transformations.4 The significant enhancement in enantiocontrol is believed to be due to carboxylate carbonyl stabilization of the intermediate metal carbene and/or to dipolar influences on substrate approach to the carbene center.

Enantioselective Intramolecular Cyclopropanation Reactions.

The exceptional capabilities of the Rh2(5S-MEPY)4 and Rh2(5R-MEPY)4 catalysts for enantiocontrol are evident in results obtained with a series of allyl diazoacetates (eq 1).5,8 Both high product yields and enantiomeric excess (ee's) are characteristic. Intramolecular cyclopropanation of (Z)-alkenes proceeds with a higher level of enantiocontrol than does intramolecular cyclopropanation of (E)-alkenes. In preparative scale reactions, less than 0.25 mol% of catalyst can be employed to achieve high yields of pure product.5

Similar success in enantiocontrol has been achieved for intramolecular cyclopropanation of homoallyl diazoacetates (eq 2).15 With these substrates the enantiomeric excesses do not extend beyond 90%, but they are virtually independent of double bond substituents.

Enantioselective Intermolecular Cyclopropenation Reactions.

The use of Rh2(MEPY)4 catalysts for intermolecular cyclopropenation of 1-alkynes results in moderate to high selectivity. With propargyl methyl ether (or acetate), for example, reactions with (-)-menthyl [(+)-(1R,2S,5R)-2-isopropyl-5-methyl-1-cyclohexyl] diazoacetate catalyzed by Rh2(5S-MEPY)4 produces the corresponding cyclopropene product (eq 3) with 98% diastereomeric excess (de).14,16

These reactions are subject to significant double diastereoselection with (+)- and (-)-menthyl diazoacetates. With ethyl diazoacetate, enantiomeric excesses are moderate (54-69% ee), but they increase up to 78% ee with t-butyl diazoacetate.14 These are the first examples of enantioselective catalytic cyclopropenation reactions.

Enantioselective Intramolecular Carbon-Hydrogen Insertion Reactions.

The suitability of Rh2(5S-MEPY)4 and Rh2(5R-MEPY)4 for enantioselective intramolecular C-H insertion reactions is evident in results with 2-alkoxyethyl diazoacetates (eq 4).9 Both lactone enantiomers are available from a single diazo ester. Other examples have also been reported, especially those with highly branched diazo substrate structures.9

Diazoacetamides are robust diazo substrates, but they generally give lower enantioselection, and regioselectivity for g-lactam formation is dependent on the substituents on carbon at which insertion occurs (e.g. eq 5).17 With N-(n-butyl)-N-(t-butyl)diazoacetamide the ratio of g:b-lactam is 88:12. A significant improvement in enantioselection (up to 78% ee) occurs with the use of the oxazolidinone analog of Rh2(5S-MEPY)4.17

Polyethylene-Bound, Soluble, Recoverable Dirhodium(II) 2-Pyrrolidone-5(S)-carboxylate.

The homogeneous Rh2(5S-MEPY)4 catalyst has been attached to a polyethylene chain that is soluble in organic solvents at about 70 °C.18 Ligand displacement of 2-pyrrolidone-5(S)-carboxylate from Rh2(5S-MEPY)4 by a soluble polyethylene-bound 2-pyrrolidone-5(S)-carboxylate produces a recoverable dirhodium(II) catalyst, PE-Rh2(5S-PYCA)4, in high yield. The effectiveness of this catalyst has been demonstrated by high enantioselection for intramolecular cyclopropanation of 3-methyl-2-buten-1-yl diazoacetate (see eq 1) in refluxing benzene solution (98% ee) and for intramolecular C-H insertion of 2-methoxyethyl diazoacetate (see eq 4) under the same conditions (72% ee). For both transformations, reactions catalyzed by Rh2(5S-MEPY)4 that occur at the same temperature give lower % ee values. Although diminished selectivity can occur with catalyst recovery and reuse under standard conditions, retention of catalyst effectiveness is achieved by using 2-3 mol % of the pyrrolidone ligand in up to seven subsequent runs with recovered, reused PE-Rh2(5S-PYCA)4.

1. Doyle, M. P. In Selectivity in Catalysis; Davis, M. E.; Suib, S. L., Eds.; American Chemical Society: Washington, 1993.
2. Doyle, M. P. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993.
3. Doyle, M. P. RTC 1991, 110, 305.
4. Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.; Simonsen, S. H.; Ghosh, R. JACS 1993, 115, 9968.
5. Doyle, M. P.; Winchester, W. R.; Protopopova, M. N.; Kazala, A. P.; Westrum, L. J. OS 1994, 73, in press.
6. Doyle, M. P.; Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C. T.; Loh, K.-L. JACS 1990, 112, 1906.
7. Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.; See, M. M.; Boone, W. P.; Bagheri, V.; Pearson, M. M. JACS 1993, 115, 958.
8. Doyle, M. P.; Pieters, R. J.; Martin, S. F.; Austin, R. E.; Oalmann, C. J.; Müller, P. JACS 1991, 113, 1423.
9. Doyle, M. P.; Van Oeveren, A.; Westrum, L. J.; Protopopova, M. N.; Clayton, T. W., Jr. JACS 1991, 113, 8982.
10. Doyle, M. P.; Brandes, B. D.; Kazala, A. P.; Pieters, R. J.; Jarstfer, M. B.; Watkins, L. M.; Eagle, C. T. TL 1990, 31, 6613.
11. Aratani, T. PAC 1985, 57, 1839.
12. Pfaltz, A. ACR 1993, 26, 339.
13. (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. JACS 1991, 113, 726. (b) Lowenthal, R. E.; Masamune, S. TL 1991, 32, 7373. (c) Müller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. HCA 1991, 74, 232.
14. Protopopova, M. N.; Doyle, M. P.; Müller, P.; Ene, D. JACS 1992, 114, 2755.
15. Martin, S. F.; Oalmann, C. J.; Liras, S. TL 1992, 33, 6727.
16. Doyle, M. P.; Protopopova, M. N.; Brandes, B. D.; Davies, H. M. L.; Huby, N. J. S.; Whitesell, J. K. SL 1993, 151.
17. Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Daniel, K. L. TL 1992, 33, 7819.
18. Doyle, M. P.; Eismont, M. Y.; Bergbreiter, D. E.; Gray, H. N. JOC 1992, 57, 6103.

Michael P. Doyle

Trinity University, San Antonio, TX, USA

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