Oxidative Lactonization of Diols

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]. 

Hiroi et al. developed a new system for the oxidative lactonization of diols using acetone as cooxidant and catalyzed by the Cp lr complex bearing an 

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Scheme 2.48 Lactone synthesis by oxidative lactonization of diols.

Second, 1,4-diols undergo intermolecular hydrogen transfer, giving lactones efficiently in acetone containing Cp Ru(P-N) catalysts the TOF of this reaction at 30 C exceeds 1,000 h (Fig. 21) [67]. The catalytic oxidative lactonization of diols is characterized by its unique chemo- and regioselectivity. The significant rate difference between primary and secondary alcohols in dehydrogenation, and the rate difference between 1,4-diols and 1,5- or 1,6-diols enable unique oxidative lactonization of triols. 

Suzuki T, Morita K, Matsuo Y, Hiroi K (2003) Catalytic asymmetric oxidative lactonizations of meso-diols using a chiral iridium complex. Tetrahedron Lett 44 2003-2(X)6... 

Scheme 2.49 Asymmetric oxidative lactonization of meso diols by lr(l) [88, 94],...

General Synthesis.— The catalyst RuH2(PPh)4 brings about the oxidative condensation of diols to lactones, in addition to the conversion of alcohols to esters. o>-Benzyloxymethyl esters are converted into lactones in 71—91% yield when treated with the hydride abstractor Ph3C BF4 or the radical cation (p-BrPh)3NSbCl6 (Scheme 59). ... 

M.C. Bagley, Z. lin, D.J. Philips, A.E. Craham, Barium manganate in microwave-assisted oxidation reactions synthesis of lactones by oxidative cyctization of diols. Tetrahedron Lett. 50 (2009) 6823-6825. 

Dehydrogenative lactonization of diols is an efficient way to various lactones (Scheme 22). ° The lactone formation is found to be catalyzed by a recoverable stable dicationic iridium complex with 6,6 -dihydroxy-2,2 -bipyridine ligands, and employs a variety of benzylic and aliphatic diols in aqueous media. In comparison with the esterification of hydroxyl acids, hydroacyloxylation of olefmic acids and Baeyer-ViUiger reaction of cyclic ketones, the dehydrogenative lactonization of diols proceeds without any oxidant hence, it is more environmentally benign and atom economical. 

Scheme 28 Enantiospecific preparation of lactones by oxidative lactonization of primary meso-diols. " ...

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... 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

With a good route to the key meso diol 128 in hand, the authors turned their attention to desymmetrization, using the known asymmetric hydrolysis of meso diacetates by Lipase AK (Scheme 23). The meso diol 128 was first converted to diacetate 140, and then hydrolyzed with Lipase AK to cleave selectively one of the two acetates, producing chiral hydroxyester 141. Oxidation, cleavage of the acetate, and lactonization yielded the (3S,4.R) lactone 129. The corresponding lactol (3S,4 )-130 was found to be the enantiomer of the compound produced in the HLADH synthesis. 

Abstract This is one of the most important classes of oxidation effected by Ru complexes, particnlarly by RnO, [RuO ] , [RnO ] and RuCljCPPhj), though in fact most Ru oxidants effect these transformations. The chapter covers oxidation of primary alcohols to aldehydes (section 2.1), and to carboxylic acids (2.2), and of secondary alcohols to ketones (2.3). Oxidation of primary and secondary alcohol functionalities in carbohydrates (sugars) is dealt with in section 2.4, then oxidation of diols and polyols to lactones and acids (2.5). Finally there is a short section on miscellaneous alcohol oxidations in section 2.6. 

A chiral complex was used in Ru(N0)Cl(salen )/02/UV/CHCl3 for oxidative desymmetrisation of meso-diols to optically active lactols and lactones, e.g. of cis-1,2 -bis(hydroxyhnethyl)-cyclohexane to (1/ , 6S, 7/ 5)-7-hydroxy-8-oxabicyclo[4.3.0] nonane, cf mech. Ch. 1 [363],... 

Oxidative cleavage of P-hydroxyethers to keto-lactones was accomplished by RuClj/aq. Na(10 )/CCl -CH3CN thus hexahydro-benzofuran-3a-diol gave the corresponding nine-membered ketolactones (R =Me, Bu, R =H, Me Fig. 5.14) [87]. 

For examples of the preparation of lactones by oxidation of diols, sec Doyle Bagheri J. Org. Chem. 1981, 46, 4806 Ishii Suzuki Ikariya Saburi Yoshikawa J. Org. Chem. 1986, 51, 2822 Jefford Wang J. Chem. Soc., Chem. Commun. 1988, 634 Jones Jakovac Org. Synth. VII, 406. For a list of reagents used to effect this conversion, with references, see Ref. 21. pp. 837-838. 

A corollary of this selectivity is the very easy transformation of diols into lactones with silver carbonate on Celite .16 During the oxidation of a diol with Fetizon s reagent, as soon as an intermediate hydroxyaldehyde is able to equilibrate with a certain proportion of hemiacetal—even if present... 

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