Reduction conjugate

Iridium-catalyzed reduction of ot,p-unsaturated ketones has been investigated most recently by the groups of Bolm and Hou, respectively. 

As Table 2 indicates, ligand 23c proved effective for substrates with large, branched groups on the beta positions. The best selectivity was obtained for 54c, which was substituted with aromatic groups on both sides of the substrate, and a large branched alkyl attached to the p position [62]. Entries 54e and 54f are encouraging and may indicate that this method could be extended to more broadly useful compounds. The investigators performed a solvent study and determined the reaction to be equally selective in toluene and dichloromethane so the former was used presumably for its industrial attractiveness. 

A broader range of substrates have been reduced with substitution at the a position of a,p-unsaturated ketones using ligand 5c [63, 64]. 

Some of the more sterically demanding substrates such as 56h were reduced with a moderate loss of enantioselectivity. 

Recently developed ligand SIPHOX 16a-d proved to be a valuable tool in the asymmetric reduction of a,(3-unsaturated acids [66]. In a complete break with what is typically observed with iridium-based N,P ligands, SiPHOX catalysts were observed to reduce the strongly coordinating carboxylic acid triethylamine salt of a methylcinnamic acid in excellent enantioselectivity and yield (Table 5). Equally surprising is the use of methanol as a solvent, which normally inhibits reductions mediated by iridium N,P catalysts. 

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A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

Reduction of "Me- CuLi2" wiiii LAH was described by Asliby and crr-workers as a o produce tlie powerful reducing reagent "Li2CuH- " [10], wbidi can be n temperature for conjugate reductions lEq. 5.3). 

Representative procedure for BujSnH/Cul/LiCI conjugate reduction [20 ... 

Representative procedure for conjugate reduction-aldol 3-CC 2- Hydroxy-[l-[tolue sulfonyl)- H-indol-3-yl]-methyl -4,4-dimethylcyclohexanone [35]... 

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... 

CONJUGATE REDUCTION OF ,P-UNSATURATED p-TOLUENESULFONYLHYDRAZONES TO ALKENES WITH CATECHOLBORANE 5P-CHOLEST-3-ENE... 

The classification is unaffected by allylic, vinylic, or acetylenic unsaturation appearing in both starting material and product, or by increases or decreases in the length of carbon chains for example, the reactions f-BuOH f-BuCOOH, PhCHgOH - PhCOOH, and PhCH=CHCH20H -PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohols. Conjugate reduction and alkylation of unsaturated... 

Conjugate reductions and Michael Alkylations of conjugated aldehydes are listed in Section 74 (Alkyls from Alkenes). 

This section contains alkylations of ketones and protected ketones, ketone transpositions and annulations, ring expansions and ring openings and dimerizations. Conjugate reductions and Michael alkylations of enone are listed in Section 74 (Alkyls from Alkenes). 

D. Conjugate Reduction of Conjugated Aldehydes, Ketones, Acids, Esters and Nitriles... 

As noted in Chapter 1, this is one of the best methods for generating a specific enolate of a ketone. The enolate generated by conjugate reduction can undergo the characteristic alkylation and addition reactions that are discussed in Chapters 1 and 2. When this is the objective of the reduction, it is important to use only one equivalent of the proton donor. Ammonia, being a weaker acid than an aliphatic ketone, does... 

The stereochemistry of conjugate reduction is established by the proton transfer to the (3-carbon. In the well-studied case of A1,9-2-octalones, the ring junction is usually trans,213... 

Reduction of tosylhydrazones of a, (3-unsaturated ketones by NaBH3CN gives alkenes with the double bond located between the former carbonyl carbon and the a-carbon.280 This reaction is believed to proceed by an initial conjugate reduction, followed by decomposition of the resulting vinylhydrazine to a vinyldiimide. 

Keywords Conjugate reduction Enolate C - C bond formation ... 

Conjugate reduction by the transition metal-hydride (TM - H) accompanied by transition metal enolate formation... 

This reaction sequence of conjugate reduction followed by aldol reaction is known as the reductive aldol reaction. In certain instances, reductive elimination from the M-TM-enolate species may occur to furnish M-enolate, which itself may participate in the aldol reaction (Scheme 3). This detour may be described as the background path or stepwise path in one-pot. Indeed, it has been reported that certain cationic Rh complexes such as [Rh(COD)(DPPB)] (COD = 1,5-cyclooctadiene, DPPB = diphenylphosphinobutane) catalyze the aldol reactions of silyl enol ethers and carbonyl compounds by serving as Lewis acids [5-8]. 

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

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