Regioselectivity carbonyl reduction

Substituted furan-2(5H)-ones are available regioselectively by reductive carbonylation of alk-l-ynes <99TL989>. 

Carbonylation proceeds in the presence of chalcogen compounds without poisoning Pd catalysts. Pd-catalyzed stereo- and regioselective carbonylative double thiolation of 1-octyne with diphenyl disulfide (3) afforded the (Z)-j6-(phenylthio)--unsaturated thioester 4 [2], The thioester 4 can be converted to 3-(phenylthio)-2-alkenal 5 by Pd-catalyzed reduction with HSnBu3 under mild conditions [3]. When propargyl alcohol was subjected to the carbonylation in the presence of either diphenyl diselenide (6) or disulfide 3, 3-phenylselenobutenolide 7 or 3-phenylthiobutenolide was obtained. The transformation involves isomerization of the acylpalladium intermediate 8 to 9 [4]. 

The sphingosine 296 has been prepared from D-mannose in 10 steps Levoglucosenone is the starting material for a synthesis of (25,3S,4i )-2-amino-1,3,4-octadecanetriol 300 (see Scheme 47), by carbonyl reduction, diastereoselec-tive cu-oxyamination and reoxidation to 297. Regioselective Baeyer-Villiger... 

The well-known reduction of carbonyl groups to alcohols has been refined in recent studies to render the reaction more regioselective and more stereoselective Per-fluorodiketones are reduced by lithium aluminum hydride to the corresponding diols, but the use of potassium or sodium borohydride allows isolation of the ketoalcohol Similarly, a perfluoroketo acid fluonde yields diol with lithium aluminum hydnde, but the related hydroxy acid is obtainable with potassium borohydnde [i f] (equations 46 and 47)... 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

More symmetrical imides may still be regioselectively reduced. In the case of geminally disub-stituted succinimidcs the stcrically more hindered carbonyl function is preferentially reduced with sodium borohydride. The regioselectivity ranges from 79 21 for the dimethyl derivative to > 95 5 for the diphenyl derivative29. For monosubstituted succinimides the selectivity of the reduction is low29, unless the substituent is an acetoxy group35-36. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

Carbonyl compounds, such as aldehydes [103, 179], (thio)ketones [31, 94, 180-183], carboxylic acids, and esters [183, 184] with 1 are reduced to alcohols after hydrolysis [5], except in stericaUy hindered cases (see Section 8.5) [185, 186]. Under the same experimental conditions the regioselective reduction of the oxirane ring with 1 gives also the corresponding alcohol [183, 187]. 

The intercalated catalysts can often be regarded as biomimetic oxidation catalysts. The intercalation of cationic metal complexes in the interlamellar space of clays often leads to increased catalytic activity and selectivity, due to the limited orientations by which the molecules are forced to accommodate themselves between sheets. The clays have electrostatic fields in their interlayer therefore, the intercalated metal complexes are more positively charged. Such complexes may show different behavior. For example, cationic Rh complexes catalyze the regioselective hydrogenation of carbonyl groups, whereas neutral complexes are not active.149 Cis-Alkenes are hydrogenated preferentially on bipyridyl-Pd(II) acetate intercalated in montmorillonite.150 The same catalyst was also used for the reduction of nitrobenzene.151... 

The [Rh(CO)2Cl]2-induced ring fission of substituted cyclopropanes 8a-b affords the rhodium complexes 9a-b via carbonylation [8]. The regioselectivity of carbonyl group insertion depends on the substituent. Reduction with NaBH4 leads to the corresponding alcohol. (Scheme 4)... 

In a similar way, a mixture consisting of 2% boron trifluoride etherate in trifluoroacetic acid and triethylsilane brings about the regioselective reduction of the acyclic carbonyl group of the diketovinyl chloride shown in Eq. 215 in high yield (>94%), but with formation of approximately equal amounts of the two possible diastereomers formed from the creation of a new chiral center.396... 

Quinazolines undergo many of the same reactions as pyrimidines, such as the modification of an amino group. Gangjee and co-workers reported the reductive alkylation of diaminoquinazolinones 141 with various aryl carbonyl compounds 142, which regioselectively produced quinazolinones 143 <00JHC1097>. 

This system fulfills the four above-mentioned conditions, as the active species is a rhodium hydride which acts as efficient hydride transfer agent towards NAD+ and also NADP+. The regioselectivity of the NAD(P)+ reduction by these rhodium-hydride complexes to form almost exclusively the enzymatically active, 1,4-isomer has been explained in the case of the [Rh(III)H(terpy)2]2+ system by a complex formation with the cofactor[65]. The reduction potentials of the complexes mentioned here are less negative than - 900 mV vs SCE. The hydride transfer directly to the carbonyl compounds acting as substrates for the enzymes is always much slower than the transfer to the oxidized cofactors. Therefore, by proper selection of the concentrations of the mediator, the cofactor, the substrate, and the enzyme it is usually no problem to transfer the hydride to the cofactor selectively when the substrate is also present [66]. This is especially the case when the work is performed in the electrochemical enzyme membrane reactor. 

The synthetic usefulness of dioxin vinylogous esters as p-keto vinyl cation equivalents was demonstrated by a variety of reductive and alkylative 1,3-carbonyl transpositions.5 7 Regioselective alkylation and hydroxylation at the a -position (and, in some cases, at the y-position)8 9 further extend the usefulness of 1,3-dioxin vinylogous ester templates in organic synthesis. 

Regioselectivity in the cathodic allyla-tion of ketones and aldehydes is greatly affected by the relative ease of the reduction of the allyl halide compared with that of the carbonyl compound. When the carbonyl compound is more easily reduced than the allyl halide, the allylation takes... 

Cathodic reduction of retinal leads to a regioselective coupling in the presence of malonic ester to produce the corresponding pinacol (Fig. 26) [129]. Chromium(III) ions facilitate the reduction and favor the regioselective coupling of conjugated dienones to pinacols. A Cr(III)-carbonyl compound complex is evidenced as the reason for the selectivity [130]. 

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