Conjugate reduction of enones

The key step in a short and efficient synthesis of pleraplysillin-1 (127) is the palladium-catalyzed cross-coupling of vinylstannane 125 with vinyl triflate 126 (see Scheme 33). This synthesis is noteworthy in two respects. First, vinyl triflate 126 is generated regio-specifically from the kinetic enolate arising from a conjugate reduction of enone 124 the conjugate reduction of an enone is, in fact, a... 

Copper-mediated conjugate reductions of enones and enoates were reported in 1988 by Stryker and co-workers (188). Stryker and Mahoney (189) showed that the reaction could be made catalytic in copper under an atmosphere of hydrogen gas however, under these conditions, overreduction was observed. In 1998, Lipshutz... 

Conjugate reduction of enones. a./ -Unsaturated ketones and aldehydes undergo 1,4-reduction in generally high yield with I equivalent of lithium aluminum hydride in the presence of 10 mole % of Cul and 1 equivalent of HMPT at -78°. The active agent presumably is LiHCuI. Cul can be replaced by mesitylcoppcr and copper(I) t-butoxide. 

Conjugate reduction of enones.1 Under phase-transfer conditions (Aliquat, NaHC03), a,0-enones undergo exclusive 1,4-reduction with Na2S204 (yields 70-85%). 

Conjugate reduction of enones. This reduction can be effected with 2 equiv. of Li(Bu)(i-Bu)2AlH (2) and of MAD. The choice of solvents can affect the selectivity. Sterically hindered ketones undergo 1,4-reduction very readily. 

Conjugate reduction of enones. In the presence of I equiv. of aluminum chloride, 1 can effect conjugate reduction of open-chain n,p-enones. usually in 75-100% yield. Cyclic enones also are reduced, but in lower yicid (50-65%). This reagent is not useful for conjugate reduction of a,p-unsaturated esters or aldehydes. ... 

Many other examples of chemoselective enone reduction in the presence of other reducible functionalities have been reported. For instance, the C—S bonds of many sulfides and thioketals are readily cleaved by dissolving metals. " Yet, there are examples of conjugate reduction of enones in the presence of a thioalkyl ether group." " Selective enone reduction in the presence of a reducible nitrile group was illustrated with another steroidal enone. While carboxylic acids, because of salt formation, are not reduced by dissolving metals, esters" and amides are easily reduced to saturated alcohols and aldehydes or alcohols, respectively. However, metal-ammonia reduction of enones is faster than that of either esters or amides. This allows selective enone reduction in the presence of esters"" and amides - -" using short reaction times and limited amounts of lithium in ammonia. 

The intemietallic hydride LaNijHe is an effective reagent for conjugate reduction of enones. Reduction of the resulting saturated carbonyl occurs very slowly with this reagent, giving high yields of the 1,4-reduction product. ... 

Conjugate reduction of enones with K-Selectride (K[5ec-Bu3BH]) is a valuable method for regiospecifically generating enolate anions. As illustrated below, the enolate species reacts with an alkyl halide to give the corresponding a-alkylated ketone in good yield. 

JOC5279>. Oxasilacyclopentane (9), in combination with its hydride adduct, rapidly reduce carbonyl compounds. The hydride adduct alone is a selective reagent for the conjugate reduction of enones <90JA5342). 

Conjugate reduction of enones. When LiAlH4 in THF is added to a slurry of Cul in THF at 0°, gas is evolved, and a deep black reagent is formed that is an active reagent for conjugate reduction of enones when the LiAlH4 /Cul/enone ratio is 1 4 1. 

Conjugate reduction of enones. The alkali metal carbonylchromates reduce a, -unsaturated carbonyl compounds to the corresponding saturated carbonyl compounds in 4d-807o yield. They are comparable to potassium hydridotetra-carbonylferrate (6, 483-486), but are simpler to prepare because chromium hexacarbonyl is a stable solid and less toxic than iron pentacarbonyl. Examples ... 

The conjugate reduction of enones is easier than that for enal (39, 40), because aldehyde carbonyl is softer than the ketone counterpart. Alkyl substituents in the a and positions of the enones interfere with conjugate reduction (39). However, treatment of a-alkylthiocyclohexenones with NaBH4 successfully gives saturated alcohols (41). It has been proposed that intramolecular H delivery from a S-coordinated borohydride is involved. A marked increase in the 1,4-reduction of enones by LiAlH(SR)3 is observed (42) (see Table 7.1). Symbiotic softening of the reagents by the thio substituents is responsible for the reversal of the alkoxy effects. 

The conjugate reduction of enones is a well known route to enolates and the conformational preferences of acyclic enones are now found to determine the geometry of the enolate produced... 

In addition to molecules containing prochiral sites, racemic molecules can participate in catalytic asymmetric transformations. In some transformations, the stereocenter is destroyed in the course of the reaction, and equilibrating prochiral intermediates are formed. An example of such a process is the asymmetric arylation of ketones (Figure 14.8C). In other cases, one of the enantiomers of the substrate reacts with the asymmetric catalyst significantly faster than the other enantiomer. In this case, an enantioenriched product is formed, and the opposite enantiomer of the reactant remains. This last process is called a kinetic resolution and is illustrated for the conjugate reduction of enones via hydrosilylation (Figure 14.8D). In this case, the top and bottom faces of the C-C double bond are diastereotopic because reaction at each face of the enone generates diastereomeric products. This section of the chapter first presents the principles that relate to reactions at prochiral centers of achiral substrates and then presents the principles that relate to reactions of racemic or meso compounds. 

In conjugate reduction of enones with other transition metals such as chromium, the rates of reduction were shown to be dependent on the conformation of the substrate, with faster reactions being observed with the cisoid forms as compared with the transoid onesJ However, with the Pd/Si/Zn system, the rigid transoid enone of cyclohexenone and the flexible enone of acetylcyclohexene are both reduced in comparable rates. This indicates that palladium interacts exclusively with the olefinic part of the enone without significant participation of the carbonyl. Interestingly, this method is highly selective for unsaturated ketones and aldehydes, as the reduction of corresponding o,jS-unsaturated carboxylic acid derivatives, such as esters, amides, and nitriles, is very slow under the conditions used. Thus, ben-zylideneacetone is selectively and cleanly reduced in the presence of methyl cinnamate, dnnamonitrile, or dnnamamide.t" ... 

The generality of the Pd/Si/Zn method, the mild reaction conditions used, and the simple and convenient experimental procednre make it a method of choice for conjugate reduction of enones. 

The second strategy involves addition of a group 14 metal hydride to palladium. For example, a combination of either tributyltin hydride or various silicon hydrides and palladium catalyst are efficient systems that affect the conjugate reduction of enones with high chemoselectivity and regioselectivity. 

Preparation of Cu-H . A reducing reagent Cu-H has been generated from copper(I) chloride and hydrosilanes and used for conjugated reduction of enone systems in 1,3-dimethylimidazolidinone at room temperature (eq 60). ... 

Tsuchiya Y, Hamashima Y, Sodeoka M. A new entry to Pchemistry catalytic asymmetric conjugate reduction of enones with EtOH and a highly enantioselective synthesis of warfarin. Org. Lett. 2006 8(21) 4851 54. 

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