Alcohols from ester reductive carbonylation

Esters. Reductive carbonylation in the presence of an alcohol or phenol leads to an ester. Substrates include organoiodonium salts and allylic alcohols. p,y-Unsaturated thioesters can be generated by the method or from allenes. Note that y-lactones are formed when allylic alcohols are carbonylated without additives. ... 

The reason why the carbonyl group in -santonin remained intact may be that, after the reduction of the less hindered double bond, the ketone was enolized by lithium amide and was thus protected from further reduction. Indeed, treatment of ethyl l-methyl-2-cyclopentanone-l-carboxylate with lithium diisopropylamide in tetrahydrofuran at — 78° enolized the ketone and prevented its reduction with lithium aluminum hydride and with diisobutyl-alane (DIBAL ). Reduction by these two reagents in tetrahydrofuran at — 78° to —40° or —78° to —20°, respectively, afforded keto alcohols from several keto esters in 46-95% yields. Ketones whose enols are unstable failed to give keto alcohols [1092]. 

Reduction of carbonyl compounds with metal hydrides or boranes a. primary alcohols from aldehydes, acids, acid halides, and esters... 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

The formation of alcohols by the reduction of aldehydes and ketones, carboxylic acids, esters and epoxides is summarized in Scheme 2.9. The change in the strength of the reducing agents, from the relatively mild sodium borohydride to the vigorous lithium aluminium hydride, reflects the difference in the electron deficiency of the carbonyl group which is being reduced. 

The reductive carbonylation of propargyl alcohols in the presence of thiols which results in P,y-unsaturated thioesters is in contrast to the formation of 5-hydroxy-2,3-alkadienoic esters from ethynyloxiranes. 

Systematics are also available for the 8 0-values of the compounds in queshon [56[ carboxyl and carbonyl functions in isotopic equilibrium with the surrounding water are, due to equilibrium isotope effects, enriched in 0 relative to this water by 19 and by 25 to 28%o, respectively. From here, the 8 0-values of natural alcohols, mostly descendants of carbonyl compounds, will have (maximally) similar 8 0-values, provided the precursors have attained isotopic equilibrium with water and their reduction has not been faster than their equilibration. Alcohols from addihon of water to C=C double bonds or from exchange of halogen functions by OH groups, typical for synthetic alcohols, will have 8 0-values close to or even below that of the water, due to kinetic isotope effects. The few available results [246, 289, 290] seem to confirm this expectation. The 8 0-values of natural (and also synthetic) esters and lactones can be, especially in the carbonyl group, extremely high (up to 50%o), probably as a consequence of an intramolecular kinetic isotope effect on the activation of the carboxyl function. 

Mukaiyama s tridentate diamino alcohol 6 is derived from the coupling of two L-proline units followed by reduction of the ester/amide carbonyl groups ent-6... 

In the asymmetric reduction of a-ketoesters, the asymmetric induction depends on the steric inequality of two moieties attached to the carbonyl group [9]. The reduction of hindered a-ketoesters yields the corresponding a-hy-droxyesters with optical purities approaching 100% ee (Eq. 26.28). This contrasts strongly with the 11% ee realized in the reduction of 7 (R= i-Pr) with neat Alpine-Borane [9b]. Alpine-Borane (from (-t)-pinene) yields (S)-alcohols in the reduction of both alkylaromatic ketones and a-ketoesters. On the other hand K-glucoride yields (R)-alcohols with aralkylketones and (S)-alcohols with a-keto esters (Table 26.27) [7]. 

Carbonylation of Alcohols and Esters. The mechanism of ttie Rh/I" catalysed alcohol carbonylation has been studied in detail. Rates decrease sharply from methanol to n-propanol. Formation of isobutyric acid as a by-product points to a p-H elimination-reinsertion sequence.This sequence has also been demonstrated for ethanol carbonylation by selective C labelling (eqn.l8). The reductive carbonylation of methanol in the presence of Col2 and PPhg generates acetaldehyde, ethanol and methyl acetate. Only diphenylether and alkanes as solvents did not decompose under the reaction conditions (17CPC,... 

Esters of general structure B can be cleaved with the same reagents described for the esters of general structure A. The multifunctionality of the resulting compounds is Umited because the carbonyl part of the functionality remains on the resin. Most type-B esters are released as alcohols from the resin (path a) but there are a few examples which obtain other derivatives of the resin-bound structures (Schemes 16,18 and 19). Path b in Scheme 16 illustrates the cleavage of methylarenes 108 on polymeric support pubhshed by Sucholeiki in 1997 [140]. Release from the resin affords addition of a palladium catalyst (Pd(OAc)2) and formate reduction. 

Alcohols can be prepared from carbonyl compounds by reduction of car boxy he acids and esters See Table 15 3... 

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