Cyclopentanones selective reduction

The selective reduction of the cyclopentanone is achieved by the reduction of both ketones with excess of Dibal-H, resulting in a bisaluminium alkoxide that is regioselectively oxidized under Oppenauer conditions by the addition of acetone. 

The sterically unbiased dienes, 5,5-diarylcyclopentadienes 90, wherein one of the aryl groups is substituted with NO, Cl and NCCHj), were designed and synthesized by Halterman et al. [163] Diels-Alder cycloaddition with dimethyl acetylenedicarbo-xylate at reflux (81 °C) was studied syn addition (with respect to the substituted benzene) was favored in the case of the nitro group (90a, X = NO ) (syrr.anti = 68 32), whereas anti addition (with respect to the substituted benzene) is favored in the case of dimethylamino group (90b, X = N(CH3)2) (syn anti = 38 62). The facial preference is consistent with those observed in the hydride reduction of the relevant 2,2-diaryl-cyclopentanones 8 with sodium borohydride, and in dihydroxylation of 3,3-diarylcy-clopentenes 43 with osmium trioxide. In the present system, the interaction of the diene n orbital with the o bonds at the (3 positions (at the 5 position) is symmetry-forbidden. Thus, the major product results from approach of the dienophile from the face opposite the better n electron donor at the (3 positions, in a similar manner to spiro conjugation. Unsymmetrization of the diene % orbitals is inherent in 90, and this is consistent with the observed facial selectivities (91 for 90a 92 for 90b). 

In hydrogenolyses with HAICU, the dimethyl acetals of cyclobutanone and cyclohexanone are cleaved more slowly than that of 3-pentanone, while those of cyclopentanone and cycloheptanone are cleaved more rapidly (Table 1), as would be expected for a carbonium ion process. The differences in rate are small, suggesting that carbonium ion character is not strongly developed in the transition state. With the dimethyl acetal of 4-t-butylcyclohexanone, the hydride addition step occurs with strongly predominating axial addition when HAlCh is used Zn(BH4)2 with TMS-Cl, and TMS-H with TMSO-Tf are less selective (Table 2). Equatorial attack predominates, however, in the reduction of the ketone itself with TBDMS-H and TBDMS-OTf. ... 

In the reductive dimerization of methyl cinnamate to a cyclopentanone [Eq. (5)], similar yields are found at the cathode [42] and with metals (sodium, THE, and TBAI, —78°C) [40]. Because of the potential selective conversion at the electrode, halides can be reduced at the cathode to carbanions in the presence of carbonyl compounds, which are reduced at more cathodic potentials. This way labile carbanions can be obtained and reacted under conditions in which the same species generated by a metalorganic route would decompose. Eor example, trichlorobromoalkane can be cathodically converted in the presence of aldehydes to a dichloromethyl anion 0°C [route a, Eq. (6)] and be trapped to form a dichlorotetrahydrofuran, but for the metallorganic route [route b, Eq. (6)] a reaction temperature of — 110°C is necessary [43]. 

In other cases, the selectivity of the traditional Meerwein-Ponndorf Verley reduction with substituted cyclopentanones is very low. One example is the reduction of a prostaglandin precursor to a 1 1 mixture of a c/.v-diol and the lactone, derived from the corresponding /rans-dioll47. 

Substituted cyclopentanes can have substituents in pseudoaxial or pseudoequatorial positions (in other words, they are somewhat like the axial and equatorial positions in a cyclohexane), but rapid equilibration means that overall we have a very flexible and labile system. As a result, reduction of 2-substituted cyclopentanones may not be very stereoselective. What selectivity there is (about 3 1) in the reduction of 2-methylpentanone with L1A1H4 favours pseudoaxial attack in the conformation drawn, as is reasonable for a small nucleophile. 

Three more general techniques have greatly improved the earlier yields. Discussion of the solid-phase adsorption method is included in more recent reviews. It probably remains the method of choice in selected cases and sometimes has results different from those of other methods. For example, the predominant reduction to cyclopentanone in the intramolecular reaction of iV-acetyl-iV-allylpropargylamine (eq 58) and the reductive ether cleavage when related ethers react on alumina (eq 59), is avoided on silica, in the presence of oxygen, with formation of the expected bicyclic products. 

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