2- hydroxy cyclohexanone, reduction

Cathodic reduction of 1,3-diphenyl-propenone leads to l-hydroxy-2-benzoyl-3,4-diphenyl cyclopentanes with exclusive cis configuration of the two phenyl groups. With l-phenyl-l-pentene-3-one the cyclodimer 2-methyl-3,5-diphenyl-4-(l-propionyl)-cyclohexanone is formed with a 100% yield in an intramolecular Michael addition via an electrogenerated base. The substituents are all in the most stable equatorial position [277]. 

YtAST REDUCTION OF Z,2-DIMETHYLCYCL0HEXANE-1,3-DI0KE (S)-(+)-3-HYDROXY-Z,2-DIHETHYLCYCLOHEXAHONE (Cyclohexanone. 3-hydrov2.2-d1inethy1-, (S)-)... 

Kenji Mori and Hideto Mori 56 YEAST REDUCTION OF 2,2-DIMETHYL- CYCL0HEXANE-1,3-DI0NE (S)-(+)-3-HYDROXY-2,2-OIMETHYL-CYCLOHEXANONE... 

Wada, M., Yoshizumi, A., Noda, Y., Kataoka, M., Shimizu, S., Takagi, H., Nakamori, S. 2003. Production of doubly chiral compound, (4R,6R)-4-hydroxy-2,2,6-trimethyl-cyclohexanone, by two step enzymatic asymmetric reduction. Appl. Environ. Microbiol., 69, 933-937. 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

Tetra-n-butylammonium triacetoxyborohydride in refluxing benzene reduced aldehydes but not acyclic ketones, the selectivity was demonstrated in competition experiments and keto aldehyde reductions. The more reactive cyclohexanones were reduced only slowly under the same conditions. The limitation of this convenient method is that proximal hydroxy groups activated the reagent enabling the... 

A serious obstacle to the use of the Julia alkenation for the synthesis of trisubstituted alkenes is illustrated in Scheme 31. Addition of cyclohexanone to the lithiated sulfone (86) gave intermediate (87), which could not be acylated under the reaction conditions because of the sterically hindered tertiary alk-oxide. Owing to an unfavorable equilibrium, (87) reverted back to starting materials. However, by reversing the functionality of the fragments a stable adduct (88) was formed in which the less hindered secondary alkoxide was acylated and the resultant -benzoyloxy sulfone (89) reductively eliminated to the alkene (90) in 54% overall yield. Trisubstimted alkenes have been generated by reductive elimination of 3-hydroxy sulfones ° but, in general, retroaldol reactions compete. 

The stereoselectivity of the hydride reduction of conjugated cyclohexenones has also been subjected to close examination from both experimental and theoretical viewpoints. Much of the work has involved polycyclic systems, e.g.. steroids which have little conformational flexibility and in which axial and equatorial directions of approach can be clearly defined. With small" hydride donors, these substrates show an even clearer preference for axial attack than the corresponding cyclohexanones. For examples involving reductions with lithium aluminum hydride and sodium borohydride, see Table 10. 3/(-Acetylcholest-5-en-7-one and cholest-2-en-l-one are notable in that the analogous saturated substrates are attacked from the equatorial direction115 l16. The reduction of 17/i-hydroxy-4-androsten-3-one (testosterone) to 4-androstene-3/1,17/j-diol with d.r. 90 10 can be compared with the sodium borohydride reduction of 17/i-hy-droxyandrostan-3-one (dihydrotestosterone) to androstane-3/ ,17/ -diol with d.r. 81 19 (see p 4030). 

If one of the heteroatoms is present as an OH group then only one nucleophile is involved and molecules such as cyanohydrins (7) are obviously made from carbonyl compounds and HCN. Hence hydroxy amine (8), needed for a ring expansion (see Chapter 30), can be made by reduction of (9) (see Chapter 8) and hence from cyclohexanone. 

The tetrahydro-l,3-oxazine (132) from cyclohexanone and aminopro-panol was converted to the diazo-intermediate (133) and cyclised using rhodium acetate to the tra i-P-lactam (134). Non-selective reduction of the ketone gave both hydroxy epimers. Progression through the sequence as outlined provided the thiol-ester phosphorane (138) possessing the required ( )-acetamidoethenyl substituent. Cyclisation in boiling toluene gave the two epimers of (139) which were separated, and deprotected to afford (+)-MM 22383 (140) and ( )-iV-acetyldehydrothienamycin (141). 

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