Cyclopentenone ketone reduction

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

Selective reduction of Ike carbonyl group of tf-cyclopentenones The reduction of a,/3-unsaturated ketones to the corresponding curbinols by complex hydrides is accompanied with concomitant saturation of the double bond. This undesired reaction is particularly noted in the case of A2-cyclopentenones. However, use of aluminum hydride (inverse addition) produces the unsaturated carbinols in satisfactory yields. 

In a route by Hoffman—La Roche workers [35] ring contraction of the cyclohexane dione (24) with sodium carbonate in mesitylene gave the cyclopentenone (25) which was elaborated to the lactone (26a) by 1,4 addition of nitromethanc, oxidative cleavage of the allyl side chain, ketone reduction and lactonisation. 

A route to the optically active lactone alcohol (14e) has been reported by Dow and Gruppo Lepetit chemists [45] in which the intermediate (40) was constructed from (5 )-(-)-malic acid and cyclised in a buffer of triethanolamine-triethanolamine hydrochloride to give the cyclopentenone (41) as the major product. The latter was hydrogenated to the cyclopentanone (42) which was then taken foward by ketone reduction to the a-hydroxyl, hydrolysis and... 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

Selective reductions This complex borohydride is particularly useful for selective 1,2-reduction of acyclic a,/ -cnones and of conjugated cyclohexenones to allylic alcohols. However, the 1,2-selectivity is less marked with conjugated cyclopentenones. The reagent reduces unhindered cyclic ketones to the more stable (equatorial) alcohols with stereoselectivity greater than that of sodium borohydride. 

In general, structural variations to the backbone of the Chirald ligand have not led to the development of more selective or reliable LAH complexes for use in asymmetric reductions. Other complexes of amino alcohols with LAH have been studied for their ability to achieve enantioselective reduction of prochiral ketones. However, in most cases the selectivities observed have been moderate. The complex of LAH with the amino alcohol (IS) reduces some enones, such as cyclohexenone and cyclopentenone, to the corresponding (5)-alcohols in high optical purities (100% and 82% ee, respectively). ... 

A stereoselective Li-NHs reduction of a cyclopentenone has been employed in two different syntheses of the cytotoxic sesquiterpene coriolin (69 Scheme 2). In one synthesis, tricyclic ketone (70) was reduced stereoselectively to alcohol (71) using Li-NHs-methanol. In the second synthesis, tetracyclic enone (72) was converted in a single step to (71). This reduction proceeds by initial cleavage of the cyclopropyl ketone unit of (72) to give ketone (70), which is then reduced to (71). 

Highly enantioselective conjugate reductions of substituted cyclopentenones and cyclohexenones were reported by Kergomard using Beauveria sulfurescens (ATCC 7159) under anaerobic conditions. The reaction takes place only with substrates containing a small substituent in the a-position and hydrogen in the -position. The saturated ketones obtained were, in some cases, accompanied by saturated alcohols. 

A bis([2.2]paracyclophane)-annelated cyclopentadiene could be synthesized via a Nazarov cyclization of the bis([2.2]paracyclophane-l,9-dienyl) ketone 136 prepared by addition of monolithiodiene 133 to ethyl formate and subsequent oxidation of the carbinol 110. The synthesis was completed by diisobutylalumi-num hydride (DIBA1-H) reduction of the resulting cyclopentenone, and dehydration with p-toluenesulfonic acid. Treatment with methyllithium gave the corresponding cyclopentadienyllithium 136-Li, which was identified by NMR spec-... 

The rearrangement of divinyl ketones to cyclopentenones (the Nazarov rearrangement) can be promoted with BF3-Et20. This transformation has recently been applied to good effect in the construction of the hydroazulene core found in guanacastepene. Other variants of the Nazarov reaction have been developed and are usually coupled with a second event, such as the reductive... 

The original discovery synthesis of the P2 domain of telaprevir utilized bicycloproline derivative 56 (Scheme 10),"° which was prepared in racemic form using a four-step, two-pot protocol starting from 2-cyclopentenone, as described by Monn and Valli." In this approach, enantiomerically pure 56 was obtained via chiral HPLC separation." Reduction of the ketone of 56 produced secondary alcohol 57, which was further reduced to 58 under Barton-McCombie deoxygenation conditions. The synthesis of P2 fragment 59 was completed by hydrogenolysis of the benzyl carbamate. 

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