Cycloisomerization/dimerization reactions

Hashmi s team41 noticed that the cycloisomerization/dimerization reactions leading to 4 or 6 required, under the same reaction conditions (1 mol% catalyst), over a week for AgNC>3, about an hour with PdCl2(MeCN)2 and only about a minute with AuC13. 

Moreover, following the cycloisomerization reaction, a tandem dimerization reaction is also possible on the same substrates under Pd11, Ag1, and Aura catalysis, leading to different substituted furans (4 or 6) depending on the nature of the catalyst used (Scheme 5.5). Indeed, from compound 3 (Scheme 5.5), palladium(II) catalysis led to a 59% yield of 4, whereas silver(I) and gold(III) catalysis led to furans 5 and 6.41... 

Vinylallene 198 itself undergoes a variety of dimerization and cycloisomerization reactions on heating at 170 °C in the gas phase [162],... 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

Other catalytic reactions involving a transition-metal allenylidene complex, as catalyst precursor or intermediate, include (1) the dehydrogenative dimerization of tributyltin hydride [116], (2) the controlled atom-transfer radical polymerization of vinyl monomers [144], (3) the selective transetherification of linear and cyclic vinyl ethers under non acidic conditions [353], (4) the cycloisomerization of (V2V-dia-llyltosylamide into 3-methyl-4-methylene-(V-tosylpyrrolidine [354, 355], and (5) the reduction of protons from HBF4 into dihydrogen [238]. 

Under optimized conditions, cycloisomerizations of a number of functionalized hept-l-en-6-ynes took place in good-to-excellent yields (Table 9.3). Heteroatom substitution was tolerated both within the tether and on its periphery. Alkynyl silanes and selenides underwent rearrangement to provide cyclized products in moderate yield (entries 6 and 7). One example of seven-membered ring formation was reported (entry 5). Surprisingly, though, substitution was not tolerated on the alkene moiety of the reacting enyne. The authors surmize that steric congestion retards the desired [2 + 2]-cycloaddition reaction to the point that side reactions, such as alkyne dimerization, become dominant. 

A modification of this system was also used in intramolecular MBH reactions (also called as aldol cycloisomerization) [71, 74]. In this reaction, optically active pipecolinic acid 61 was found to be a better co-catalyst than proline, and allowed ee-values of up to 80% to be obtained, without a peptide catalyst. The inter-molecular aldol dimerization, which is an important competing side-reaction of the basic amine-mediated intramolecular MBH reaction, was efficiently suppressed in a THF H20 (3 1) mixture at room temperature, allowing the formation of six-membered carbocycles (Scheme 5.14). The enantioselectivity of the reaction could be improved via a kinetic resolution quench by adding acetic anhydride as an acylating agent to the reaction mixture and a peptide-based asymmetric catalyst such as 64 that mediates a subsequent asymmetric acylation reaction. The non-acylated product 65 was recovered in 50% isolated yield with ee >98%. 

The cycloisomerization of allenyl ketones was initially described as being catalyzed by rhodium(I) or silver(I) by Marshall et al.21 The activity of copper, silver, and gold for this reaction was first compared in two papers published later (Scheme 12.7).22 In the case of copper and silver, only a cycloisomerization was observed (Table 12.4, entries 1 and 2) with gold, a dimer is obtained as well (entry 3). 

Finally, the cycloisomerization of 4-vinylcyclohexene (a butadiene dimer) to bicyclo[3.3.0]-2-octene (6) was found to occur at 250° over a silicophosphoric acid catalyst (11), along with a very large amount of hydrogen transfer (ethylcyclohexenes, methylethylcyclopentenes, ethylbenzene) and polymerization, a reaction closely related to that of limonene (5). A much better yield of the same hydrocarbon (6) was obtained from 1,5-cyclooctadiene (72% at 200°) with the same catalyst (25). 

Best results were obtained with Rh(PR3)3Cl and [Rh(COD)Cl]2 catalysts in the presence of an excess of electron-poor triaryl phosphines to avoid undesirable dimerization/oligomerization processes. The proposed reaction mechanism involves the formation of the Rh-vinylidene complex followed by the intramolecular endo-dig cyclization. The protodemetallation of intermediate I seems to be the more plausible path, whereas the formation of the Rh-oxacarbene complex II was excluded because all attempts to generate lactones by using N-hydroxysuccinimide failed and the cycloisomerization product was the only product obtained (Scheme 10). 

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