Reductive Cyclization of 1,6-Diynes and 1,6-Enynes

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

The products of reductive cyclization incorporate two non-exchangeable hydrogen atoms. Homolytic and heterolytic hydrogen activation pathways may now be discriminated on the basis of hydrogen-deuterium crossover experiments. Reductive cyclization of the indicated nitrogen-tethered enyne under a mixed atmosphere 

The acquisition of cycloisomerization products without deuterium incorporation is inconsistent with a hydrometallative mechanism. Furthermore, the ab- 

5 mol% Catalyst Loading X = NTs, 52% Yield (42% Alkyne Reduction) X = O, 60% Yield 

From the seminal studies of Sabatier [43] and Adams [44] to the more recent studies of Knowles [45] and Noyori [46], catalytic hydrogenation has been regarded as a method of reduction. The results herein demonstrate the feasibility of transforming catalytic hydrogenation into a powerful and atom-economical method for reductive C-C bond formation. Given the profound socioeconomic impact of al-kene hydroformylation, the development of catalysts for the hydrogen-mediated 

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Another reaction is reductive cyclization of 1,6-diynes and 1,6-enynes using hydrosilanes as a hydrogen source in AcOH. Triethylsilane is used as the hydrogen donor for this reaction [142], The reaction can be understood by the formation of vinylpalladium bond 350 via the insertion of alkyne 349 to the Pd—H bond in 328. Then intramolecular alkyne insertion gives vinylpalladium 351, which is hydro-genolysed with Si—H to give the 1,3-diene 352 by transmetallation and reductive... 

Scheme 4-302. Reductive cyclization of 1,6-enynes and diynes using...

Reductive Cyclization of 1,6- and 1,7-Dienes, Diynes, Enynes and Arenes via Zirconacycles and Titanacycles... 

Table 22.11 Reductive cyclization of assorted 1,6-diynes and 1,6-enynes.

Another reaction is reductive cyclization. 1,6-Diynes and 1.6-enynes undergo reductive cyclization using hydrosilanes as a hydrogen source in AcOH. The 1,6-diynes 91 and 95 are converted into the 1,2-dialkylidenecyclopentane derivatives (1,3-dienes) 94 and 96. Triethylsilane is used as a hydrogen donor for the reaction[48]. The reaction involves the formation of a vinylpalladium bond in 92 via the insertion of an alkyne into the Pd—H bond, followed by the alkyne insertion to give 93, which is hydrogenolyzed with Si—H to give the 1,3-dienes 94 and 96. 

An illustration of the preparation of six-membered rings by enyne cycloisomerizations is found in Trost s total synthesis of (-t-)-cassiol (113) (Scheme 6-19) [44]. The key step of this synthesis involved conversion of enyne 111 to 1,4-diene 112. Although a mixture of diastereomers is produced, the offending stereocenter is not found in the natural product, allowing both diastereomers of 112 to be used. A reductive diyne cyclization (114 115) was recently described as the key step in a total synthesis of ( )-siccanin (116) [45]. Hydropalladation of the terminal alkyne, insertion of the internal alkyne, hydride transfer to palladium, and reductive elimination are proposed to account for the observed reaction. 

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