Cyclopentadienyl(3,5-dimethoxybenzyl)(nitrosyl)(triphenylphosphine)rhenium1

(+)-(S)

[109283-17-2]  · C32H31NO3PRe  · Cyclopentadienyl(3,5-dimethoxybenzyl)(nitrosyl)(triphenylphosphine)rhenium  · (MW 694.78) (-)-(R)

[109362-39-2]

(reagents for enantioselective synthesis of organic compounds with chiral methyl groups1)

Physical Data: mp 204-205 °C; [a]21589 ±116° (CH2Cl2, c 0.3-0.6 mg cm-3).

Solubility: sol CH2Cl2, benzene, ether, and THF; slightly sol hexane.

Form Supplied in: bright orange crystals.

Analysis of Reagent Purity: IR, and 1H, 13C, and 31P NMR spectroscopies, microanalysis, and polarimetry.1

Preparative Methods: reaction of the methyl ester (+)-(S)-(Cp)Re(NO)(PPh3)(CO2Me) (S-1)2 with 3,5-dimethoxyphenylmagnesium iodide in toluene at -24 °C gives 3,5-dimethoxybenzoyl complex (+)-(S)-(Cp)Re(NO)(PPh3)(CO(3,5-(MeO)2C6H3)) (S-2; 85%). Refluxing (+)-(S)-(2) with BH3.THF or BD3.THF in THF gives the title reagents (+)-(S)-(3) or (+)-(S)-(3)-a-d2 (95-84%). The opposite enantiomers (-)-(R)-(3) or (-)-(R)-(3)-a-d2 can be similarly made from (-)-(R)-(1).1

Purification: crystallization from benzene/hexane.

Handling, Storage, and Precautions: the solid reagent is stable for days in air. However, it should be prepared, stored, and reacted under a dry nitrogen atmosphere.

Compounds with chiral methyl groups (RCHDT) play important roles in the elucidation of biological and abiological reaction mechanisms.3 The title compound can be utilized to prepare chiral 3,5-dimethoxytoluene, which can in turn be degraded to CHDTCO2H. The enantiomeric purity of the latter can be assayed enzymatically.1 Analogs (Cp)Re(NO)(PPh3)(CH2R), which can be similarly synthesized, can usually be converted to the corresponding RCHDT compounds.

In practice, (+)-(S)-(3)-a-d2 and Ph3C+PF6- are allowed to react to give the alkylidene complex (+)-(S)-[(Cp)Re(NO)(PPh3)(=CD(3,5-(MeO)2C6H3)]+PF6- ((+)-(S)-(4t)-a-d1; 91%) (eq 1). Addition of NaBT4 gives (+)-(S,S)-(3)-a-d1t1 (87%). Subsequent reaction with HBr gives (+)-(R)-(Cp)Re(NO)(PPh3)(Br) ((+)-(R)-(5); 93%) and (R)-dimethoxytoluene-a-d1t1 ((R)-(6); 85%) with retention of configuration at carbon and rhenium. The latter is treated with O3 to give, after addition of NaOH, the chiral acetate salt (S)-CHDTCO2-Na+ in 93% ee. The opposite enantiomer, (R)-CHDTCO2-Na+, is made from (-)-(R)-(3)-a-d2 in 86% ee.1

Thus the chiral rhenium auxiliary allows the highly stereoselective introduction of all hydrogen isotopes. The generalization of this methodology to other substrates is shown in eq 2. No complications are encountered for cases where R = n-alkyl or aryl. The method fails when R is a secondary alkyl group, as the reaction of (Cp)Re(NO)(PPh3)(CH2CHR1R2) and Ph3C+PF6- gives an alkene complex (b-hydride abstraction).4

There are several elements of synthetic flexibility. In most cases, both enantiomers of the target can be generated from the same enantiomer of the precursor alkyl complex. For example, the hydrogen isotopes can be introduced in different orders. Alternatively, depending upon reaction temperature, either of the two alkylidene complex Re=C geometric isomers (7k) and (7t) (eq 2) can be generated in >90% isomeric purity. The hydrogen isotope nucleophile attacks from a direction anti to the bulky PPh3 ligand in each case, giving different diastereomers.3 These in turn give different product enantiomers. Finally, if a benzylic rhenium complex is treated with a deuterated or tritiated acid in the rhenium-carbon bond-cleavage step, some aryl C-H bonds are also labeled. The optically active bromide complex (+)-(R)-(5) can be recycled to the methyl complex (+)-(S)-(Cp)Re(NO)(PPh3)(Me) without racemization.5 The latter is easily converted to the methyl ester (+)-(S)-(1),2 or directly to alkyl complexes.4


1. O'Connor, E. J.; Kobayashi, M.; Floss, H. G.; Gladysz, J. A. JACS 1987, 109, 4837.
2. Agbossou, F.; O'Connor, E. J.; Garner, C. M.; Quirós Méndez, N.; Fernández, J. M.; Patton, A. T.; Ramsden, J. A.; Gladysz, J. A. Inorg. Synth. 1992, 29, 211.
3. Floss, H. G. In Mechanisms of Enzymatic Reactions: Stereochemistry; Frey, P. A., Ed.; Elsevier: New York, 1986; pp 71-88.
4. Kiel, W. A.; Lin, G.-Y.; Bodner, G. S.; Gladysz, J. A. JACS 1983, 105, 4958.
5. Ramsden, J. A.; Peng, T.-S.; Gladysz, J. A. BSF 1992, 129, 625.

Tang-Sheng Peng & J. A. Gladysz

University of Utah, Salt Lake City, UT, USA



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