Rearrangements lactonization

Enzymatic Baeyer-Villiger oxidations have been studied for a long time some very useful applications in natural product synthesis date back more than two decades. For example, prochiral (3A, 5,S )-4-hydroxy-3,5-dimethylcyclohexanone was successfully oxidized using a CHMO from Acinetobacter sp. NCIMB 9871. In this case the seven-membered ring formed rearranges spontaneously into the thermodynamically more stable y-lactone. The rearranged lactone has been used in the synthesis of natural products such as tirandamycin or calyculin A (Fig. 25) [157-159],... 

As shown in Equation (179), a tandem Claisen rearrangement-lactonization involving the C-3 side chain of furan 292 was employed for a concise synthesis of hyperolactone C <2003JNP1039>. Although the product yield was low, the reaction created two contiguous quaternary carhon centers in one step. 

Quinic acid (246) can be transformed with acetic acid-sulfuric acid into the rearranged lactone 247. By the same principle, the C-(hydroxymethyl)cyclohexanetetrol 248 is isomerized by acetic acid-sulfuric acid into the isomer 249, which can be isolated in 14% yield from the reaction mixture. ... 

The lactonization of 4-phenyl-4-pentenoic acid (345) upon treatment with PhI(OAc)2 has been reported (Scheme 3.137) [432]. The mechanism of this reaction includes electrophilic lactonization induced by the addition of the iodine(III) electrophile to the double bond of substrate 345 followed by 1,2-phenyl migration leading to the final rearranged lactone 346. 

In the HNMR spectrum of compound 13.2, the C-13 methylene group doublet was shifted up field (5 3.58, 7= 6.5 Hz) in comparison with the non-rearranged lactone 11.44 in its acetyl derivative 13.3 the signal was shifted downfield (5 4.03 ppm), as expected. 

NaBH4 reduction of compound 11.25 104) afforded the rearranged lactone 13.2, which was formed by lactone ring opening of the initially formed 3-deoxy-6 3,7(3-dihydro-8-epilactarorufin A, followed by ring closure onto the 8a-hydroxy group. 

Intramolecular oxygenation reactions were also used in the asymmetric synthesis of different substituted lactone derivatives. Using chiral X -iodane 5c, lactonization of 4-aryl-4-pentenoic acids 31 gave rearranged lactones through phenonium ion participation in 56% yield, albeit in only 4% ee (Scheme 14) [57]. Another example of lactonization involving enantioselective... 

Thallium(iii) acetate with (130) gives the rearranged lactone (131), whose structure was established by AT-ray analysis lead tetra-acetate reacts in an analogous manner. The endo-epimer of (130) gives similar rearranged lactones. Lactol (132) in aqueous alkaline solution gives (133) with chlorine, and further transformations of (133) are noted. Previous attempts to prepare (134) by treatment of (135) with base have given mainly (136). By use of dimethylform-amide as solvent, conversion of (135) into (134) proceeds efficiently. Full... 

Schmalz et al. [202] recently reported a tandem anionic homo-Fries rearrangement/ lactonization [203] for the synthesis of cyclo-mumbaistatin analogue 436 (Scheme 105). 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Oxiranones (a-lactones) 81JA686, 80AG(E)276), e.g. (6), are highly reactive, readily polymerizing (Scheme 18), possibly via a zwitterion (18). Such a species (19) would also account for the rearranged products (20) and (21) from (22 Scheme 19). 

The lactone A was also used as starting material in the synthesis of the primary prostaglandins via an allylic substitution-semi-pinacolic rearrangement sequence (Ref. 2). 

Photochemical rearrangements of enol esters, enol lactones, and enol ethers... 

Photochemical oxacarbene formation, 307 Photochemical rearrangements of cross-conjugated cyclohexadienones, 330 Photochemical rearrangements of enol esters and enol lactones, 339... 

Acylisoxazol-5-ones (129), which are -diketones, on being heated in alkaline medium undergo acyl-lactonic rearrangement to form stable isoxazole-4-carboxylic acids (130). ... 

Rearrangements and other side-reactions are rare. The ester pyrolysis is therefore of some synthetic value, and is used instead of the dehydration of the corresponding alcohol. The experimental procedure is simple, and yields are generally high. Numerous alkenes have been prepared by this route for the first time. For the preparation of higher alkenes (> Cio), the pyrolysis of the corresponding alcohol in the presence of acetic anhydride may be the preferable method." The pyrolysis of lactones 9 leads to unsaturated carboxylic acids 10 ... 

Isolated problems of racemization, rearrangement or dehydration should not overshadow the fact, however, that the range of species amenable to enantiomeric two-dimensional GC is very wide indeed, including not only terpenes and lactones. 

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

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