Subject Clemmensen reduction

Intramolecular cyclisation of a 4-arylbutanoic acid system is also an important step in a convenient synthesis of the polycyclic system, chrysene, which is formulated and described in Expt 6.12. Here, methyl cinnamate is first subjected to reductive dimerisation to give methyl meso-ft,y-diphenyladipate, which is accompanied by some of the ( + )-form. The meso isomer (16) is the most easily isolable and cyclisation occurs smoothly in sulphuric acid to yield the diketone 2,1 l-dioxo-l,2,9,10,ll,18-hexahydrochrysene, which is obtained as the trans form (17) as shown in the following formulation. Clemmensen reduction of this ketone followed by dehydrogenation (in this case using selenium) completes the synthesis of chrysene. 

The reduction takes place at the surface of the zinc catalyst. In this reaction, alcohols are not postulated as intermediates, because subjection of the corresponding alcohols to these same reaction conditions does not lead to alkanes. The following proposal employs the intermediacy of zinc carbenoids to rationalize the mechanism of the Clemmensen Reduction ... 

During the enantioselective total synthesis of denrobatid alkaloid (-)-pumiliotoxin C by C. Kibayashi et al., an aqueous acyinitroso Diels-Alder cycloaddition was used as the key step. In the endgame of the total synthesis, the c/s-fused decahydroquinolone was subjected to the Clemmensen reduction conditions to give a 2 1 epimeric mixture of deoxygenated products in 57% yield. Subsequent debenzylation converted the major isomer into 5-ep/-pumiliotoxin C. 

Scheme 3 Olefin (29) prepared from dienone (26) by standard organic reactions was converted to bromohydrin derivative (30), which on subjection to photolysis and dehydrohalogenation yielded ketal (32), whose conversion to a,P unsaturated ketone (34) was accomplished by hydrolysis, bromination and dehydrobromination respectively. The cyanation of (34) followed by hydrolysis and esterification produced ester (35), which on Clemmensen reduction and oxidation afforded lactone (37). Reduction of (37) followed by oxidation and esterification gave ketoester (38), which was converted to (39).

The identity of the ketone (179) could not be confirmed by direct comparison owing to the non-availability of an authentic specimen of the ketone (179). In order to confirm the identity of the ketone (179), its carbonyl group was eliminated by Clemmensen reduction [75]. The resulting deoxygenated material without purification was subjected to oxidation with chromic acid in acetic acid and demethoxylation with silicon... 

Why do we need three different ways to do the same thing Because each of these methods involves a different set of conditions. The Clemmensen reduction employs acidic conditions. The method we learned just now (desulfurization with Raney nickel) employs neutral conditions. And the method in the upcoming section will employ basic conditions. As we move through the course, we wiU see times when it won t be good to subject an entire compound to acidic conditions, and we win see other times when it won t be good to subject an entire compound to basic conditions. When in doubt whether it is bad to use acidic conditions or basic conditions, you can always just use a desulfurization with Raney nickel, which employs neutral conditions. 

Alternatively, benzene could have been subjected to Friedel-Crafts acylation with benzoyl chloride to give benzophenone. Clemmensen or Wolff-Kishner reduction of benzophenone would then furnish diphenylmethane. 

The main interest in dithio-ketals and -acetals has been in connection with their hydrogenolysis by Raney nickel to give the corresponding hydrocarbons, as an alternative to the Clemmensen or Wolff-Kischner reduction on the parent carbonyl compound. This subject has been thoroughly reviewed [90]. Hydrogenolysis of thioketals has also been effected by hydrazine [91, 92, 93] and by alkali metals in liquid ammonia [94]. 

---