Oxidative diol lactonization approach

Complementary to the oxidative diol lactonization approach, a substrate containing both ketone and ester functionalities may undergo reduction to liberate the desired lactone product following ring closure. Noyori and coworkers demonstrated that Ru-BINAP complexes were excellent catalysts for the asymmetric reduction of ketones with neighboring carboxylic acid and ester functionalities capable of undergoing the desired lactonization in high yields and selectivities (Scheme 2.50) [103, 104],... 

However, these methods suffer from low activities and/or narrow scope. Uemura and coworkers [74,7 5] reported an improved procedure involving the use of Pd(OAc) 2 (5 mol%) in combination with pyridine (20 mol%) and 3 A molecular sieves (500 mg per mmol of substrate) in toluene at 80 °C. This system smoothly catalyzed the aerobic oxidation of primary and secondary aliphatic alcohols to the corresponding aldehydes and ketones, respectively, in addition to benzylic and allylic alcohols. Representative examples are summarized in Table 5.7. The corresponding lactones were afforded by 1,4- and 1,5-diols. This approach could also be employed under fluorous biphasic conditions [76]. 

The environmentally benign synthesis of lactones has attracted attention because of their importance in natural product chemistry. The oxidative cyclization of diols via carbon-oxygen bond formation is the most well-known approach for the synthesis of lactones [70]. 

Two syntheses of racemic 2,3-dihydrotriquinacen-2-one (380) have been described. The first approach consisted in the selective monoketalization of diketone 364 with 2,2-dimethylpropane-l, 3-diol and Baeyer-Villiger oxidation of 375 (Scheme 60).357 Although two lactones were produced, 376 could be freed of its isomer by selective alkaline hydrolysis. Diisobutylalumium hydride reduction of 376 afforded 377, the acetate of which was converted by acid treatment to 378. Ketaliza-tion of this isomeric mixture, followed by hydrolysis, mesylation, and treatment with potassium f-butoxide in dimethyl sulfoxide afforded diene ketal 379. Deketa-lization then liberated the desired ketone. 

An approach to lactone [12] similar in concept to that just described, but not requiring a resolution, involved asymmetric Diels-Alder reaction of (benzyloxymethyl)cyclopentadiene [21] with the chiral ester of acrylic add and 8-phenylmenthoI (22), The adduct [22] was obtained in undetermined but apparently quite high e.e. Oxidation of the ester enolate of [22], followed by lithium aluminum hydride reduction, gave diol [23] as an... 

The second method uses the pregnane derivative XI as a starting material. This compound, on hydroxylation with osmium tetroxide, afforded the diol Xlla. This diol was then converted to the androstane analogue X. The same approach was independently published also by Hondo and Mori (3). As a by-product of hydroxylation of olefin XI with osmium tetroxide, we obtained 2B,3B-diol XIV and, from this, the lactone XV. However, when we treated XII (a corresponding diacetate, respectively) with trifluoroperacetic acid we found that oxidation of the side chain surprisingly proceeded much faster than oxidation of the B ring. Thus we obtained not only compound X but also an intermediate, compound XHIb, and on hydrolysis compound Xllla, that is the androstane analogue of castasterone ... 

The routes leading from lactone A have the advantage of a chiral source of starting materials. With the two chiral centers at C24 and C25 set, the problem reduces down to elaborating the B ring with the appropriate substituents. An early solution was provided in an unusual cyclization of the B ring via an intramolecular Michael addition to the unsaturated aldehyde formed from a nitrile oxide 1,3-dipolar cycloaddition to the allyl methyl ketal of lactone A [76]. This clever use of relative stereocontrol provided by the highly constrained and predictable transition states of both key reactions unfortunately resulted in a low yield. A more conventional approach conceptualized the addition of a sulfoxide [77] to 2 to yield a masked diol-ketone precursor which cyclizes under acidic catalysis. Elimination of the sulfoxide permitted the introduction of the hydroxy substituent at C19 of the spiroketal. 

Oxidative hydroboration 91) of lactone 11.49 afforded a mixture of four lactarorufins (Scheme 20), in which diols 11.30 and 11.33, arising from a attack of diborane, largely predominated (more than 90%). The same type of stereoselectivity was observed for other addition reactions, i.e. epoxidation, osmylation, hydrogenation (775), (704), 43) to 2,9, 3,4- or 6,7-double bond of lactaranolides and marasmanes. Apparently, the tricyclic structures of these substrates provided enough conformational and steric bias to direct approach of reagents from the same side as the bridgehead protons H-2 and H-9. However, when the double bond was located in a different position, exceptions were observed 98). 

Hiroi et al. have reported a novel approach to 8-lactones by an oxidative lactonization of 1,5-diols using an amino alcohol-based iridium bifunctional... 

A couple of template-directed approaches have been developed for the synthesis of mevalonolactone [90]. In the first approach, the spiro-fused lactone 225 constructed from diacetone-o-glucose was subjected to a stereoselective epoxida-tion and then reduction to provide diol 226 (Scheme 46). Cleavage of the acetals followed by exhaustive oxidation allowed the cleavage of the carbon skeleton from the template, providing (/ )-mevalonolactone 10 in moderate yield. 

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