[133684-62-5]  · C9H12BrMoNO  · Bromo(crotyl)(cyclopentadienyl)(nitrosyl)molybdenum  · (MW 326.04)

(reagent for stereocontrolled synthesis of b-methyl homoallyl alcohols via crotyl addition to aldehydes)

Physical Data: mp ~150 °C (with dec).

Solubility: sol most polar organic solvents; very sol methylene chloride.

Form Supplied in: orange crystals; currently no commercial source.

Handling, Storage, and Precautions: indefinitely stable at rt under nitrogen or argon. The crystals can be handled in air for short periods with no significant decomposition.

Additions of crotyl organometallics to aldehydes provide a particularly effective route for the stereocontrolled synthesis of b-methyl homoallyl alcohols. CpMo(NO)(halide)(h3-crotyl) reagents complement the crotylboron and crotyltitanium reagents, which are more reactive but can be more sensitive to decomposition by moisture (particularly the titanium complexes). As solids they have an indefinite shelf life and solutions are not particularly air-sensitive, although they are best handled under an inert atmosphere.

There are several methods of reagent preparation;1-4 the most useful involves several straightforward steps via high yield reactions from the (E)- or (Z)-crotyl halide (eq 1).4 (Z)-Crotyl Chloride can be prepared readily from cis-2-butenol (commercially available or from hydrogenation of 2-butynol) by reaction with Triphenylphosphine and Hexachloroacetone.5

Since the (E)-crotyl complex is the stable form and the half-life for conversion of (Z) to (E) is ~0.4 days at rt in solution, the steps involving addition of crotyl halide and LiCp to the (Z)-crotyl complex are best carried out at 0 °C. An alternate efficient route to the (Z)-crotyl complex is via hydride reduction of [CpMo(CO)(2-butyne)2]BF4 under an atmosphere of CO to yield the CpMo(CO)2(crotyl) complex6 followed by treatment with NO+ and halide.2 The various halides can be easily interconverted by treatment with excess NaX or LiX in acetone. Another preparation uses the commercially available [CpMo(CO)3]2 as the starting organomolybdenum reagent with cis- or trans-crotyl halides.7 Liebeskind8 has reported that use of diphenylphosphinates instead of halides may be useful for analogs of crotyl reagents.

When the (Z)-crotyl reagent is initially prepared it usually contains some (<15%) of the (E)-isomer. Since the (Z)-isomer is less soluble (particularly for the iodide and bromide), recrystallization (CH2Cl2/pentane at -15 °C) allows separation of 99% pure material. This step is often not necessary because the (Z)-isomer reacts much faster with aldehydes than the (E)-isomer; consequently, the de of the product is not affected to a great degree. This feature appears to be common to other crotyl reagents, since (Z)-crotyl boronates also react faster than their (E)-analogs.9 One should note in this preparation that the addition of NO+ yields exclusively the isomer with the NO group trans to the methyl group. This tends to weaken the Mo-C bond on the methyl-substituted terminus of the crotyl ligand. An h1-crotyl is thus readily formed (k &AApprox; 0.5 s-1 at 25 °C). This allows interconversion of conformers of the reagent in solution. Characterization by NMR can be complicated by the presence of resonances for two conformers (exo:endo &AApprox; 2:1 for the (Z)-crotyl-iodide complex).

The reactivity of the CpMo(NO)(halide)(crotyl) complexes decreases in the order OTs > Cl > Br >> I. The iodide and bromide readily form large crystals from methylene chloride and are more easily handled than the chloride and tosylate. The greater reactivity of the bromide thus may make it the reagent of choice. The (Z)-crotyl complex yields the syn-homoallylic alcohol (eq 2), whereas the (E)-crotyl complex yields the anti-isomer (eq 3), as one might anticipate based on a chair-like transition state. With the racemic crotyl complexes, both of the enantiomers of (2) and (3) shown in eqs 2 and 3 are produced as well.

The reaction rates are slow by comparison with those of allyltitanium reagents, which are often used at low temperatures. The reactions are faster in methylene chloride than in chloroform. Since they are second-order reactions, the more concentrated the solutions, the higher the rate. The reactions are effective for alkyl, aryl, and a,b-unsaturated aldehydes, but not for ketones. Room temperature reactions typically require less than an hour for CpMo(NO)(Br)[(Z)-crotyl] and 12 hours for CpMo(NO)(Br)[(E)-crotyl]. The reaction rates with a-substituted aldehydes are slower and the more reactive tosylate may be required; nevertheless, the selectivity of the reaction with the bromide is high, but may take several days.

After attack of the crotyl on the bound aldehyde, a proton is required to remove the newly formed homoallylic alcoholate from molybdenum. In initial reports, methanol was added to the reaction mixture as a proton source. With slower reacting alcohols, problems can sometimes be encountered owing to hemiacetal or acetal formation. The water present in wet methylene chloride is sufficient to provide the needed proton for the alcohol and also generates a relative insoluble [CpMo(NO)X(OH)] dimer. The convenience of this reagent lies in the facility with which the reagent can be removed from the reaction mixture by filtration (or passage through a short silica gel column), which yields a solution of product and any remaining starting aldehyde. This approach also does not require carefully dried solvents.

Enantiomerically pure (neomenthylCp)Mo(NO)(Cl)[(E)-crotyl] complexes produce the anti-b-methyl homoallylic alcohols in high enantiomeric purity (>98% ee; 92% de).1 Although it has been unsuccessful with the parent CpMo(NO)(X)(allyl) complex, the crotyl and 2-methallyl complexes can be resolved as the camphorsulfonate complexes and converted back to the halides.10,11 These reactions also yield the anti-b-methyl homoallylic alcohols in high ee.

Variants of these reagents have been utilized by Liu et al. in stereoselective 1,3-diol (eq 4) and 1,3,5-triol syntheses.7,12,13

1. Faller, J. W.; John, J. A.; Mazzieri, M. R. TL 1989, 30, 1769.
2. Faller, J. W.; DiVerdi, M. J.; John, J. A. TL 1991, 32, 1271.
3. Faller, J. W.; Linebarrier, D. L. JACS 1989, 111, 1937.
4. Faller, J. W.; Shvo, Y.; Chao, K.; Murray, H. H. JOM 1982, 226, 251.
5. Allen, S. R.; Green, M.; Norman, N. C.; Paddick, K. E.; Orpen, A. G. JCS(D) 1983, 1625.
6. Magid, R. M.; Fruchey, O. S.; Johnson, W. L. TL 1977, 2999.
7. Vong, W.-J., Peng, S.-M.; Lin, S.-H.; Lin, W.-J.; Liu, R.-S. JACS 1991, 113, 573.
8. McCallum, J. S.; Sterbenz, J. T.; Liebeskind, L. S. OM 1993, 12, 927.
9. Hoffman, R. W.; Kemper, B. T 1984, 40, 2219.
10. Faller, J. W.; Nguyen, J. T.; Ellis, W.; Mazzieri, M. R. OM 1993, 12, 1434.
11. Faller, J. W.; Chase, K.; Mazzieri, M. R. Appl. Organomet. Chem. 1994, in press.
12. Vong, W.-J.; Lin, S.-H.; Liu, R.-S.; Lee, G.-H.; Peng, S.-M. CC 1990, 1285.
13. Vong, W.-J., Peng, S.-M.; Liu, R.-S. OM 1990, 9, 2187.

John W. Faller

Yale University, New Haven, CT, USA

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