Single cycloisomerization

Although the conversion of 63—>67 adequately expresses the utility of palladium-catalyzed cycloisomerizations for the construction of complex polycycles, the single-step, palladium-mediated conversion of compound 68 to the novel polyspirocycle 6930,31 (Scheme 15) can perhaps be regarded as the paragon of this chemistry. In this striking transformation, chemo- and regioselective... 

A new synthetic route for functionalized polyhydroxyalkyl-pyrimidines starting from unprotected aldoses and based on montmorillonite K-10 catalysis and solvent-free microwave irradiation conditions, has been reported by Yadav et al,m Thus, reaction of D-glucose and D-xylose with semicarbazide or thiosemicarbazide (186) in the presence of montmorillonite K-10, under microwave irradiation, proceeded via domino cycloisomerization, dehydrazination, and dehydration of the intermediate semi- or thiosemicarbazones (187) to afford l,3-oxazin-2-ones or l,3-oxazine-2-thiones (188) in one single step and in yields between 79% and 85% (Scheme 34). Other mineral catalysts tested, such as silica gel and basic alumina, were far less effective for this transformation and only silica gel was active at all, giving low yields (15-28%) of compounds 188a-d. The l,3-oxazin-2-ones(thiones) thus synthesized were subsequently converted into the target pyrimidines by reaction with aromatic... 

Stereoinduction was observed, as in the formation of 74 (Equation (46)) as a single diastereomer 1,3-stereo-induction was not successful. Most substrates contained only methyl-substituted olefins, leading to terminal alkenes. In the case of the cycloisomerization of an //-propyl-substituted enyne, a modicum of selectivity with respect to olefin geometry was exhibited 73 was produced in an isomeric ratio of 1 3.5. The authors do not specify whether the (E)- or (Z)-geometry was preferred. 

An intramolecular palladium-catalyzed cycloisomerization of enyne 170 was used to access the antifungal agent, chokol C (Scheme 43).102 The choice of ligand and catalyst was essential to the efficiency of the Alder-ene reaction. Enone 171 was obtained as a single olefinic isomer resulting from migration of only Ha during the cycloisomerization reaction. 

In particular, the copper-promoted cycloisomerization of unsaturated alkynes bearing a stabilized nucleophile was found to be a general method that allows the cyclization of a variety of 5-acetylenic-stabilized carbanions by using catalytic amounts of base and copper [52]. This copper-catalyzed reaction was applied to disubstituted alkynes such as 43 and converted to the (Z)-isomer 44 as a single product (Scheme 18). This result further supports... 

At first glance bisdiene substrates in which the two 1,3-diene subunits are substituted differently (e.g.. Scheme 6,17) appear to be improper candidates for Pd-catalyzed cycloisomerization, as they would probably lead to a mixture of isomers (e.g., 18). This is known for the linear dimerization of simple substituted 1,3-dienes (e.g., isoprene or piperylene). The attempted selective cross-coupling of different 1,3-dienes usually affords a complex mixture of isomeric products (vide infra). Nonetheless, the Pd-catalyzed cy-clization of bisdiene 17 does not form any of the isomeric 18 structures, but instead affords the single enediene 19 in near quantitative yield (95%). 

Six-membered dienes with an exocyclic double bond can also be obtained by gold-catalyzed cycloisomerization of 1,6-enynes. This transformation is stereospecific i.e., substrates with defined double-bond geometries afforded the products as single stereoisomers (Scheme 4-23). Low temperatures and electron-withdrawing... 

Gold(I)-catalysed allene-vinylcyclopropane cycloisomerization has been reported to give the tricyclic framework of the protoilludanes in a single step involving cyclopropane ring expansion and a Prins cyclization (Scheme 122). ... 

The skeletal rearrangement of 1,7-enynes is an extension of the cycloisomerization reaction of 1,6-enynes. 1,7-Enynes undergo single cleavage skeletal rearrangement... 

A new synthesis of monocyclic cross-conjugated carbotrienes ([Sjdendralenes) was presented by de Meijere and coworkers (Scheme 2.19) [30], which included palladium-catalyzed cycloisomerization of 2-bromoalka-l, -dienes with tetra-substituted methylenecyclopropane end groups and the corresponding 1,6- and 1,7-enynes. Carbotriene 119 underwent DTHDA cycloaddition with Ph-TAD in a domino fashion to give a single diastereomer of the pentacyclic aza-heterocycle 121 in 81% yield. 

Cycloisomerization of methyl-substituted 1,6-diene is also catalyzed by tin(rv) triflate (Equation (8.8)). DFT computations proposed that the mechanism does not involve the direct addition of the tin(IV) cation to a double bond because the catalyst regeneration step would be energetically unfeasible [24]. The active catalyst is a hydrated triflate salt where water molecule plays a decisive role to enable the smooth completion of the catalytic cycle. The diastereoselectivity observed in the cycloisomerization was associated with the transition-state geometries. DFT calculations also showed that protonation and deprotonation occur on a single face of the substrate. These considerations, correlated to the experiments, showed that Brpnsted superacids are not effective in Lewis superacid catalysis. 

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