Labelling cycloisomerization

With regard to the mechanism of the cycloisomerization, Fiirstner et al. found strong evidence of a metallacyclic intermediate. By labeling the allylic position of enynes 46 and 48, they showed that reactions yielding traws-annulated rings 47 transferred the deuterium atom to the exocychc double bond (eq. 1 in Scheme 10), whereas c -annulated rings 49 formed with complete preservation of the position of the deuterium atom (eq. 2 in Scheme 10). This corresponds well to a metallacycUc... 

Marshall et al. noted that under the catalysis of Ag+ or Rh+, 1,2-allenyl ketone or aldehyde 417 may undergo cycloisomerization to afford furans 418. The reaction proceeded via the interaction of Ag+ or Rh+ with the relatively electron-rich C=C bond in the allene moiety followed by nucleophilic attack of the carbonyl oxygen [187]. Through a labeling study, it was found that the reaction proceeds by the mechanism shown in Scheme 10.162 [188]. 

Double cyclization of iodoenynes is proposed to occur through a Rh(I)-acetylide intermediate 106, which is in equilibrium with vinylidene lOS (Scheme 9.18). Organic base deprotonates the metal center in the course of nucleophilic displacement and removes HI from the reaction medium. Once alkenylidene complex 107 is generated, it undergoes [2 + 2]-cycloaddition and subsequent breakdown to release cycloisomerized product 110 in the same fashion as that discussed previously (Scheme 9.4). Deuterium labeling studies support this mechanism. 

The same products are accessible by silver-catalyzed cycloisomerization of allenic ketones. Marshall and Bartley327 used AgNOs/silica gel in hexane to convert the allenic ketones 384 into the furans 386 with excellent yields (Scheme 112). Deuterium labeling experiments were interpreted in terms of the intermediate 385 which seems to arise from the coordination of silver catalyst to the allenic double bond distal to the carbonyl group. Again, gold precatalysts can be used with much lower catalyst loadings than their silver counterparts (see Section 9.12.4.3). 

Cycloisomerization of 1,6-enynoate catalyzed by [(C5H5)Ru(MeCN)3]PF6 proceeds smoothly under mild reaction conditions to give a seven-membered ring compound in excellent yield (Eq. 5.27) [41]. In this reaction, the insertion of a C-H to form a Jt-allylmthenium intermediate is supported by deuterium-labeling studies. 

A mechanism which involved the allylic carbon-hydrogen bond activation of the alkene moiety was proposed for the cycloisomerization of 1,6-diyne to alkylidenecy-cloheptene on the basis of stereochemical consideration and deuterium labeling experiment (Scheme 12.7). 

The alcoholic solvent was essential for this catalytic cycloisomerization [27]. On the basis of studies using the known ruthenium hydrides and deuterium-labeling substrates, a mechanism involving an intermediary ruthenacyclopentane was proposed (Eq. 12.25). 

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