Hydroxy-esters => alkenes

The considerable Lewis acidity of bis(oxazoline)-copper(II) complexes held promise for catalyzing the ene reaction, a process that usually requires strong Lewis acids. Indeed, these catalysts effect a highly selective ene reaction between a variety of alkene partners and glyoxylate esters to produce a-hydroxy esters in good yield, Eq. 210 (245). The ene reaction between cyclohexene and ethyl glyoxylate proceeds in excellent diastereoselectivity and enantioselectivity, Eq. 211. As a testament to the Lewis acidity of these complexes, it is noteworthy that... 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

In practice, reduction of 35 (—2.43 V vs SCE) in the presence of 3,5-dimethylphenol as a proton donor, tetra- -butylammonium hexafluorophos-phate as the supporting electrolyte, and DMF as the solvent, led to the y-hydroxy ester 40 and lactone 41 [22]. No sign of any material resulting from cyclization onto the alkene was detected. It was concluded that radical cyclization does not occur in this instance, and that the homogeneous electron transfer rate exceeds that of a 5-exo-trig radical cyclization, thereby implying the operation of either a radical anion or carbanion cyclization pathway. 

Dipolar cycloaddition reactions between nitrile oxides and alkenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazolines, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, cc,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

Carbonylation of epoxides.4 The epoxide of a 1-alkene undergoes carbony-lation under catalysis with Co2(CO)8 in the presence of K2C03 (1 equiv.) in ethanol at moderate temperatures to afford (3-hydroxy esters. A by-product is the ketone formed by rearrangement of the epoxide. This reaction provides an essential step in the synthesis of the cyclopentenone 3 from the epoxide (1) of ethyl 10-unde-cenoate. 

There are two common ways to accomplish an asymmetric reaction. Either a second chiral center is created in a molecule under the influence of an existing chiral center in that molecule or a chiral reagent acts on a prochiral substrate to create a new chiral center. The conversion of chiral a-keto esters to di-, astereomeric a-hydroxy esters is an example of the first type of asymmetric reaction, and the asymmetric hydroboration of alkenes with chiral boranes is an example of the second type (Fig. 1). 

Asymmetricglyoxalate ene reactions.1 In the presence of 4 A molecular sieves (MS), methyl glyoxalate undergoes enantioselective ene reactions with 1,1-disub-stituted alkenes when catalyzed by la or lb. The former is superior in reactions involving a methyl hydrogen, whereas the latter is superior in reactions involving a methylene hydrogen. The reaction can provide oc-hydroxy esters in 70-95% yield and 85-98% ee. 

Monoesterification of HO(CH OHAlkenes react with diols under oxidative carbonylation conditions catalyzed by PdCl, and CuCl, to give hydroxy esters (equation I). Internal alkenes show similar reactivity. 

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