Cyclopentenones selective reduction

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. 

Utility of NaBH4-CeCl3 selective reduction is illustrated by the conversion of cyclopentenone to cy-clopentenol in 97% yield and only 3% of cyclopentanol, although conjugate reduction of cyclopentenone systems by most hydride reagents is usually highly favored (Scheme 33). 

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. 

Reductions - The use of AIH3 selectively to reduce the carbonyl group in a series of A cyclopentenones has been described. Selective reduction of the carbonyl group in a,6 unsaturated aldehydes is reported, using 5% Osmium on Carbon as hydrogenation catalyst. ... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Chiral 4,4-dialkyl-l-cyclopentenones.1 The chiral bicyclic lactam 2, derived from levulinic acid and 1, on monoalkylation exhibits slight if any selectivity regardless of the electrophile. However, a second alkylation exhibits high endo-selectivity. This product (3), after reductive cleavage, furnishes a keto aldehyde that is cyclized by base to a chiral 4,4-disubstituted-2-cyclopentenone (4). Either antipode of 4 can be prepared by the sequence of alkylation. 

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). ... 

Molecular orbital calculations have suggested that cyclopentenone is intrinsically more x one to conjugate reduction than cyclohexenone " and thus is a good substrate on which to test new 1,2-selective reagents. The selectivity of reduction of both these enones with the best of the new reagents together with the results for 9-BBN-H, the previous reagent of choice, are tabulated for comparison (Table 2). 

In his first publication in this area, Luche found samarium trichloride and CCTium trichloride (hydrated forms) to be especially effective in the selective conversion of a,j8-unsaturated ketones to allyhc alcohols (Luche, 1978), even in the case of 2-cyclopentenone, which tends to undergo 1,4-addition (essentially 100% reduction was observed with all reagent systems). 

Carbonylation of spiropentanes, affording cyclopentenones, was catalyzed by a rhodium(I) complex (Scheme 2.29) [45]. First, the less substituted C-C bond of spiropentane 31 added oxidatively to rhodium(I) to form spirocyclic rhodacy-clobutane. Insertion of carbon monoxide generated rhodacyclopentanone. Then, the less substituted methylene carbon selectively migrated onto rhodium by P-carbon elimination to convert the spirocyclic skeleton into a six-membered rhodacycle. Finally, reductive elimination furnished 3-methylenecyclopentanone, which isomerized to the enone 32 under the reaction conditions. 

In the area of carbocyclic nucleoside antibiotics, hydrolysis of the racemic esters 40 (R= n-Bu or ii-CeHis) by the lipase from Candida rugosa proceeds with very high enantiomeric selectivity, and from the resolved materials both enantiomers of aristeromydn were made by an established route. The authors report that a previous similar method (Vol.21, p. 182) is not as enantioselective. In a new synthesis of neplanocin A (43), the alcohol 41, derived from D-ribose, was converted to the cyclopentene 42 using an intramolecular insertion reaction of an alkylidene carbene. The new stereocentre in 42 was mostly of the wrong P-configuration, but could be corrected by a process of desilylation, oxidation and borohydride reduction. The biosynthesis of neplanocin A (43) and aristero-mycin has been reinvestigated, and the cyclopentenone 44 has been proposed as an intermediate, which is converted to aristeromycin via neplanocin A without any bifurcation. The 3-deaza-analogue 45 of 5 - or-aristeromydn has been prepared, and the antiviral activity of it and of the 7-deaza-compound (Vol.27, p. 235) are reported. ... 

Finally, Cramer and co-workers described an alternative route to classical Pauson-Khand reaction for the synthesis of cyclopentenones. The proposed procedure involves a reductive Ni -catalyzed [3+2] cycloaddition between aryl enoates and internal alkynes. More interestingly, the use of a chiral NHC led to a highly enantioselective reaction [eqn (10.38)]. Note that with unsymmetric alkynes the reaction is also regioselective. A plausible mechanism was proposed with the hypothesis that facial-selective coordination and incorporation of the enoate are controlled by a single chiral side chain of the carbene. 

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