Cyclic enol ethers, ring contraction

A 12-membered cyclic enol ether (26) has been synthesized by transacylation of (8) or directly from erythromycin [320, 321]. It was initially reported as a minor component in culture broths from which erythromycin had been crystallized [322]. This ring-contracted derivative (26) has also exhibited potent GI prokinetic activity [315, 323]. 

Although numerous examples of successful RCM reactions have been demonstrated, a few limitations and/or side-reactions have been uncovered. Some cases where the RCM reaction proceeds with complications are depicted in Scheme 18. Sometimes RCM reactions are competitive with alkene isomerization. For example, the unexpected formation of 162 from precursor 160 was attributed to alkene isomerization (affording 161), followed by RCM to afford the ring-contracted compound 162. Later investigators went on to exploit this observation for the synthesis of cyclic enol ethers. Treatment of the allyl ether 164 with a ruthenium carbene complex catalyst affords the RCM... 

Dipolar Cycloaddition. The principal use of p-bromobenzenesulfonyl azide is in 1,3-dipolar cycloaddition reactions with functionally substituted alkenes. The reagent has been used at ambient temperature and pressure to convert simple trimethylsilyl and methyl enol ethers of cyclic ketones to ring-contracted p-bromobenzenesulfonimidates, and thence to the corresponding amides, esters, or acids (eqs 1 and 2). 

Cyclic nitrones generated by [4+ 2]-cycloaddition of nitroalkenes undergo various, synthetically very valuable reactions. Thus, Denmark et al. have developed an elegant access to different enantiopure, 3- and 3,4-substituted pyrrolidine derivatives by reductive ring contraction of the cyclic nitrone resulting from a hetero Diels-Alder reaction [389,390]. Upon reaction of -2-nitrostyrene 4-51 with the chiral enol ether 4-52 in the presence of the bulky Lewis acid MAPh (4-53), three diastereomeric cycloadducts 4-54, 4-55 and 4-56 were formed. Hydrogenolysis of the main product 4-54 yielded the desired pyrrolidine 4-57 in excellent optical purity and allowed nearly quantitative recovery of the chiral auxiliary (Fig. 4-12) [391]. It is noteworthy that the nature of the Lewis acid catalyst, especially its steric demand, decisively influences the stereochemical course of such cycloadditions [392]. 

Aromatic sulfonyl azides react with enol ethers of cyclic ketones to form arenesulfonyl imidate esters (96) with ring contraction, the addition-rearrangement process is very stereospecific (Scheme 63). 

The study of the Diels-Alder adducts of levopimaric acid has continued with an examination of the structure and stereochemistry of the adducts with cyclopentenone and cyclopent-l-ene-3,5-dione. The major product with cyclo-pentenone is the endo,cis adduct (83). The enedione gives a mixture of enolic endo,cis adducts whose stereochemistry was determined by photocyclisation to give compounds such as (84). A correlation was also achieved with the benzo-quinone adduct through a Favorskii-type ring-contraction of the epoxide (85) to (86). The 13(14) double bond of these adducts is hindered to oxidation, excepting the adduct with acetylenedicarboxylic acid. Condensation of 12-hydroxymethylabiet-7(8)-en-18-oic acid with formaldehyde gives the cyclic ether (87). 

Arenesulfonyl azides react at ambient pressure with enol ethers of simple cyclic ketones to give ring contracted arenesulfonylimidate esters in good yields (equation 99)90. The addition-rearrangement is highly stereoselective as shown in equations 100-102. 

At high pressure ( kbar) the normally more sluggish i-butyldimethylsilyl enol ethers of cyclic ketones react in good yield to afford the ring contracted product (eq 3). ... 

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