Clemmensen reduction, modified

W-Methylpiperidine, 52, 127 3-Methyl-3-sulfolene, in Diels-Alder reaction, 50, 48 MODIFIED CLEMMENSEN REDUCTION CHOLESTANE, 53, 86... 

Uang et al. reported a synthesis of staurosporinone (293) starting from arcyriarubin A (349). Oxidative photocyclization of bisindolylmaleimide 349 in the presence of a catalytic amount of iodine in THF/acetonitrile led to arcyriaflavin A (345) in 85% yield. Finally, using modified Clemmensen reduction conditions, arcyriaflavin A (345) was transformed to staurosporinone (293) in 68% yield (795) (Scheme 5.254). 

Because of carbonium ion generation, aromatic aldehydes and ketones can usually be reduced more easily than the corresponding aliphatic compounds. However, a modified Clemmensen reduction is an effective method to reduce isolated aliphatic carbonyl groups directly to methylene groups, and typical examples are shown in equations (4)-(6)." ... 

Toda, M., Hayashi, M., Hirata, Y., Yamamura, S. Modified Clemmensen reductions of keto groups to methylene groups. Bull. Chem. Soc. 

Deoxygenation of ketones. A modified Clemmensen reduction uses zinc and A1C1.1 6H2O in aqueous THF. Hydrochloric acid is generated in situ. On the other hand, ultrasound promotes the reduction with Zn-HOAc in a selective manner (of 3-oxosteroids in the presence of ketone group at C-17 or C-20). Transpositional reduction of steroidal 4-en-3-ones (to 3-enes) can be achieved in 15 minutes. 

Styrenes. A modified Clemmensen reduction of aryl ketones using Zn(Hg) and some ethanol in refluxing formic acid gives styrenes ( -form major 5 examples, 69-83%). 

The disadvantages associated with the Clemmensen reduction of carbonyl compounds (see 3 above), viz., (a) the production of small amounts of carbinols and unsaturated compounds as by-products, (h) the poor results obtained with many compounds of high molecular weight, (c) the non-appUcability to furan and pyrrole compounds (owing to their sensitivity to acids), and (d) the sensitivity to steric hindrance, are absent in the modified Wolff-Kishner reduction. 

Common catalyst compositions contain oxides or ionic forms of platinum, nickel, copper, cobalt, or palladium which are often present as mixtures of more than one metal. Metal hydrides, such as lithium aluminum hydride [16853-85-3] or sodium borohydride [16940-66-2] can also be used to reduce aldehydes. Depending on additional functionahties that may be present in the aldehyde molecule, specialized reducing reagents such as trimethoxyalurninum hydride or alkylboranes (less reactive and more selective) may be used. Other less industrially significant reduction procedures such as the Clemmensen reduction or the modified Wolff-Kishner reduction exist as well. 

A modified Wolff-Kishner reduction employing hydrazine in glycol has been used to prepare 10-phenyldecanoic acid from the 10-keto acid (70%) and palmitic acid labeled with C14 at carbon atom 6 from the corresponding 5-keto acid. As in the Clemmensen reduction, the thiophene nucleus is unaffected. ... 

Ethylthiophene may be obtained in 91% yield by a modified Wolff-Kishner reduction of 2-acetylthiophene. Other thiophene ketones, also aldehydes, have been converted in the same way in 70% to 90% yields. Reduction by the Clemmensen procedure gives 38% to 55% yields. °°... 

If an achiral ferrocene derivative is converted to a chiral one by chiral reagents or catalysts, this may be called an asymmetric synthesis. All asymmetric syntheses of ferrocene derivatives known so far are reductions of ferrocenyl ketones or aldehydes to chiral secondary alcohols. Early attempts to reduce benzoylferrocene by the Clemmensen procedure in (5)-l-methoxy-2-methylbutane as chiral solvent led to complex mixtures of products with low enantiomeric excess [65]. With (25, 3R)-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol as chiral modifier for the LiAlH4 reducing agent, the desired alcohol was formed with 53% ee (Fig. 4-9 a) [66]. An even better chiral ligand for LiAlH4 is natural quinine, which allows enantioselective reduction of several ferrocenyl ketones with up to 80% ee [67]. Inclusion complexes of ferrocenyl ketones with cyclodextrins can be reduced by NaBH4 with up to 84% enantioselectivity (Fig. 4-9 b) [68 — 70]. 

---