Transannular ring contraction

In analogy to Edstrom s experiments, the nine- and ten- membered ring lactams underwent regio and stereoselective transannular ring contractions to give the corresponding indolizidinones and quinolizidinones, respectively (vide supra Scheme 56) (Table 21) [61]. 

Lithium aluminum hydride reduction of 6,7-diphenyldibenzo[e,5 ][l,4]diazocine (40 R = H) affords a ring-contracted product, apparently the result of transannular ring contraction of an intermediate reduction product (Scheme 2) <59JOC306>. 

In an earlier study the authors proposed a [3.2.0] bicyclic sulfonium salt 8 as the reactive intermediate in the trimethylsilyl iodide mediated ring contraction of 4-methoxythiephane <1996T5989>. Enantiomerically pure thio-lane derivatives were synthesized via a ring contraction of a seven-membered sulfur heterocycle by nucleophilic transannular substitution <2000TA1389>. The thiepane derivative 15, derived from d-sorbitol, was converted into the dimesyl derivative 16 following deprotection under acidic conditions. Treatment of 16 with sodium azide in DMSO at 120°C yielded the corresponding thiolane as a mixture of two diastereoisomers, 17a and 17b, in a 5 1 ratio (see Scheme 1). 

Unsaturated ketones, ring-contracted ketones, and bicyclic ketones resulting from transannular insertion are the main products isolated in the oxidation of cycloalkynes.738 Product distribution was interpreted in terms of an oxirene-a-ketocarbene equilibrium. 

Attempted dehydrobromination of dibromodiazocine 95 with sodium methoxide resulted in transannular reaction and ring contraction to give... 

In thiepanes 89, 90, and 92, transannular attack at C3 or C4 could lead to a mixture of polyhydroxylated tetrahy-drothiopyrans or tetrahydrothiophenes. However, by the reaction of substrates 89 (or 90) and 92 with Me3SiI, 91 and 93 were obtained exclusively (free of any five-membered cyclic sulfides), respectively, through a seven- to six-membered ring-contraction reaction. In both cases, as predicted for an Sn2 transannular cyclization and due to the presence of a -symmetric axis (Scheme 11), only one diastereoisomer was obtained. Episulfonium salt was proposed to be formed by a stereo- and regiospecific process, followed by a ring contraction toward the more stable tetrahydrothiopyran derivative. 

When structural elucidations of natural products of low molecular weight were done by chemical methods, unexpected transannular reactions occasionally made such work extremely difficult. Phenomena were observed, which could only be explained by reactions of functional groups in a ring with one another producing ring enlargement or ring contraction reactions, or, in some cases, by equilibria between open and closed systems. Such transannular reactions depend on the reaction conditions as well as the structures of the substrates. 

There are only few known ring-contraction reactions of heterocines with three heteroatoms. They lead to more favorable smaller ring systems or to bicyclic or bridged products of transannular transformations. Examples of analogous photo- and thermal intramolecular transformations are discussed in Section 14.08.5.1. 

The steroidal diazepine (15) differs greatly in reactivity from 10 and fails to undergo the characteristic ring contractions and transannular reactions of the latter.19 A number of reactions of the precursor 14 have, however, been reported.38... 

There have been relatively few applications to the contraction of larger rings. Irradiation of solutions of 4-diazo-/ra j-bicyclo[6.1.0]nonan-5-one afforded the strained carboxylate derivatives (107 XR = OH, OMe) in ca. 22-45% yield.Small to medium ring diazo ketones afford the ring-contracted carboxylic acids (108 n = 4-10) in 25-95% yield on photolysis in dioxane-H20 or THF-H20. Thermolysis of the diazo ketones in aniline at 150-160 C gave the anilides of (108) in 78-91% yield. Transannular reactions of the ketocarbene intermediates can be a complication under some conditions. 4-Carboxy[8]paracyclophane (109) has been prepared (25%) by the photochemical method. ... 

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