Subject ring contraction

Other approaches to alkylidenecycloproparenes have been attempted without success. Aromatization of appropriate alkylidenecyclopropanes or their precursors could not be realized, and flash vacuum pyrolysis of methylene phthalide and 3-methylene-2-coumaranone afforded rearrangement products rather than alkylidenecycloproparenes via extrusion of 002. The photochemical or thermal decomposition of the sodium salt of benzocyclobutenone p-toluenesulfonyl hydrazone led to products derived from dimerization of the intermediate benzocy-clobutenylidene, or from its reaction with the solvent, but no ring-contracted products were observed. When the adduct of methylene-l,6-methano[10]annulene to dicyanoacetylene (249) was subjected to Alder-Rickert cleavage, phenylacety-lene (250) was formed, which derives reasonably from the parent 234. ... 

Other fluoroaromatic compounds such as fluorobenzene, trifluorotoluene and their derivatives may be elaborated to more complex aromatic compounds by directed metallation reactions (in itself, the subject of another large review [322-324]). Wakselman and co-workers described the conversion of 3-tri-fluoromethylphenol into 2-(trifluoromethyl)-l,3-cyclopentadienone, an intermediate they used to synthesise angularly trifluoromethylated steroid analogues [325]. The reaction, which involved an interesting ring contraction reaction, occurred with rather low efficiency (Eq. 122) [326]. 

It is noteworthy that both components are highly reactive and both required an in situ generation. The cycloadduct 7-56 was then subjected to a reductive ring contraction, acetylation, and a highly diastereoselective bishydroxylation to yield 7-58 which upon several protecting group transformations gave man-nostatin A 7-57 in enantiomerically pure form (Fig. 7-13). 

The photochemistry of aqueous 2-iodophenol was the subject of a subsequent study [19]. Although ring contraction, carbene formation and photohydrolysis took place in this case too, they all were minor pathways (

comparison with homolytic C -1 cleavage forming phenyl radicals and I" atoms (

radical anions. It was concluded that the heterolytic dehalogenation mechanism observed for aqueous 2-chloro- and 2-bromophenol is overruled in the case of 2-iodophenol by a homolytic one promoted by the comparatively weaker carbon-halogen bond [19]. 

The ring contraction of bridged a-bromo ketone 581 1has been the subject of considerable synthetic application.112) The somewhat related behavior of lactam 59113) under conditions of alkaline fusion is also interesting.114) Diene 60 forms a crystalline maleic anhydride adduct, a dark purple picrate, and a brick red adduct with 1,3,5-trinitrobenzene. 

In Chapter 2, M. Bohle and J. Liebscher (Humboldt University, Berlin) review ring contractions of heterocycles by sulfur extrusion, which includes the elimination of various sulfur species all leading to a ring contraction containing one less member. This is the first comprehensive review of a subject that is of preparative as well as theoretical importance. 

A subtle substituent effect is evident in the reactions of (159 equation 66) when the amine (R = alkyl) is subjected to acid-induced rearrangement it gives the hydride migration product (160), whereas the amide (R = acyl) reacts almost exclusively by ring contraction. ... 

In some cases, the seven-membered ring is subject to contraction, as in the example below.21... 

As in the case of the / -series, the a-anomer with a free hydroxy group at C2 also showed good diastereoselectivity (13 1) in the Simmons-Smith cyclopropanation with diethylzinc/ diiodomethane in fert-butyl methyl ether at 0 C. Several substituted allylic ethers, e g. 70, were subjected to this reaction with success. While the auxiliary can be easily removed by a ring-contraction method to give cyclopropylmethanol derivatives, this methodology provides an efficient method to prepare both enantiomers. 

Ireland utilized a sulfide ring contraction process for the ring-forming step of his synthesis of 47 (see Scheme 1.16) The diethyl acetal of 5-hydroxyhexanal (73) was converted to the trichloroethyl carbonate and the acetal hydrolized to produce aldehyde 74 in 86% yield. Addition of the zinc enolate of N,N-dimethylethanethioamide (75) to 74 then afforded an intennediate hydroxy thioamide which was subjected to acylation and reductive carbonate cleavage to yield 76 (53%). Acylation with chloroacetyl chloride was followed by ring closure to give the macrocycle 77 (24%). 

Goodman has reviewed neighboring-group participation in Volume 22 of this Series,366 and this subject will therefore not be discussed comprehensively in the present article. However, Goodman specifically excluded from his review the formation of anhydro sugars by oxide ion displacements, and also the formation of anhydronucleosides ( cyclonucleosides ). These topics will therefore be discussed, together with ring contractions and alkoxyl participations, because most of the literature on these subjects has not been reviewed previously. 

In the chemistry area virtually every position on the ring and on the side chain of taxol has been subjected to structural modifications and ring contractions and ring expansions have also been employed in attempts to generate improved analogues. This work has been described in several reviews and the interested reader is referred to these for more information. 

An alternative to SO2 expulsion is via the intermediate tetrathiacyclophane, generated by oxidative cyclization of a tetrathiol, which upon desulfurization afforded the dithiacyclophane <01JA4704>. Subsequent methylation with (MeO)2CHBF4, followed by the Stevens rearrangement gave the ring-contracted, Ws-thiomethyl ether that was S-methylated and subjected to a Hofmann elimination affording 3, which is in a 1 20 equilibrium with 4. 

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