Chemoselective unsaturated esters

Branched-regioselective hydroformylation of unsaturated esters has been achieved [41]. The use of the phosphaadamantane ligand 1, which is readily available from acetylacetone and phenylphosphine (Eq. 1), proved particularly useful in terms of reaction rate, regio-, and chemoselectivity [42-44]. 

Hydroformylation of a range of 1,1-di- and 1,1,2-trisubstituted unsatur-ated esters yields quaternary aldehydes (Table 1, entries 1-8). Hence, the regiochemistry-directing influence of the electron-withdrawing ester function overcompensates Keuleman s rifle. Furthermore, hydroformylation of 1,2-disubstituted unsaturated esters occurred with high a-selectivity and chemoselectivity (Table 1, entries 9 and 10). As a side reaction hydrogenation of the alkene has been observed [41]. 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

Bennett, S.M. etal. Studies on the Chemoselectivity and Diasteroselectivity of Samarium(II) Iodide Mediated Transformations of Carbohydrate Derived co-Halo-a.fl-Unsaturated Esters. 2.1 1998 [106]... 

Owing to its radical nature, this addition reaction can take place with different kind of alkenes. This is examplified in Scheme 12 in which the reaction products 74,75, and 76 illustrate the regioselectivity and the chemoselectivity of the addition reaction with different substrates such as enol ethers, a, -unsaturated esters and a, -unsaturated vinyl esters. 

The transformation of P-ketoester 20 into a,P-unsaturated ester 21 requires the reduction of the ketone chemoselectively in the presence of the ester. Sodium borohydride (NaBH4) is the standard reagent for this type of transformation. Subsequent reaction of the sterically hindered secondary alcohol with benzoyl triflate " provides a good leaving group in P-position to the ester moiety. Elimination under basic conditions provides the a,p-unsaturated ester 21 in 50 % yield over three steps. 

The second compovtnd has an a,P-unsaturated ester so we are into aldol-style chemistry and here Klin the Wittig looks good, mainly because of the chemoselectivity needed in the aldol step. The =Oi ate) equivalent must react with an aldehyde but not with a ketone and the phosphonium ylid... 

DIBAL was used for the conjugate reduction to produce aluminum enolates in the presence of MeCu catalyst [39]. Unlike strong bases fhat readily deprotonate the a-hydrogen of carbonyl compounds, fhis mefhod tolerates a ketone carbonyl and its a hydrogen, and was fhus chemoselective as well as quantitatively reducing fhe a,/ -unsaturated ester (Scheme 6.19). 

The hydrolysis of hydroxy, amino or unsaturated esters is usually accompanied by side reactions, loss of chirality or isomerization. Various esters have been selectively hydrolysed at room temperature and in high yields under high pressure in the presence of V-methylmorpholine or Pr2NEt. For example, the hydrolysis of the p,Y-unsaturated diester 105 into p-hydroxyester 106 occurred chemoselectively in 100% yield at high pressure in methanol solution subsequent high-pressure induced hydrolysis of 106, in CH3CN/H2O (60 1) as medium, afforded the desired hydroxy acid 107 as a single product (Scheme 7.27). The usual aqueous procedures produced a mixture of products. 

S. M. Bennett, R. K. Biboutou, Z. Zhou, and R. Pion, Studies on the chemoselectivity and diastereoselectivity of samarium(II) iodide mediated transformations of carbohydrate derived co-halo -a, 3-unsaturated esters, Tetrahedron, 54 (1998) 4761-4786. 

The yields lie between 60 and 90 %, and in most cases the branched isomer 11 is formed preferentially (11 12 up to 6 1). Substituents at the propargyl position of 10 reduce the regioselectivity, and the presence of propargy-lic oxygen substituents even leads to an inversion of the selectivity in favor of the linear coupling products. The chemoselectivity is impressively underlined by the reaction of 13 with the fl,y5-unsaturated ester 14 to give exclusively 15 in 70 % yield (Scheme 5). 

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