Zhang enyne cycloisomerization

Enynes are cycloisomerized regio- and enantio-selectively with a Rh complex with phosphine ligands. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 297, Springer International Publishing Switzerland 2014 

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A highly stereoselective kinetic resolution process for Rh-catalyzed enyne cycloisomerization has also been developed by Zhang et al. [41]. This transformation has enabled the highly enantioselective synthesis of polyfunctionalized tetrahydrofurans and lactones with two or three adjacent stereocenters and it is regarded as a major breakthrough in enynes cycloisomerization and in kinetic resolution (Scheme 7). 

Recently, the transition-metal-catalyzed enanti-oselective enyne cycloisomerization has been reported.99 Cao and Zhang reported that, in the presence of catalytic amounts of [Rh(bicpo)Cl]2 and AgSbFe, the enantioselective cycloisomerization of the 1,6-enynes 50 gave the functionalized lactams 51 in good yields with high ee values (Scheme 17).99a Hatano et al. reported that, in the presence of catalytic amounts of palladium(II) and (i )-SEG-PHOS, the asymmetric cycloisomerization of the 1,6-enyne 52 gave the tetrahydrofuran derivative 53 in 99% yield with >99% ee (Scheme 18).99b It should be noted that the quaternary chiral center is constructed with extremely high ee in almost quantitative yield. 

Zhang, L., Sun, J., Kozmin, S. A. (2006). Gold and platinum catalysis of enyne cycloisomerization. Advanced Synthesis Catalysis, 348, 2271-2296. 

Chen, Z., Zhang, Y.-X., Wang, Y.-H., Zhu, L.-L., Liu, H., Li, X.-X., Guo, L. (2010). Gold catalyzed diastereoselective cascade allylation/enyne cycloisomerization to construct densely functionalized oxygen heterocycles. Organic Letters, 12, 3468-3471. 

Even though not strictly speaking belonging to enyne cycloisomerization, an alkyne and an alkene can react intermolecularly with each other provided the alkyne is properly activated. Zhang and co-workers reported a number of such cycloadditions where a gold-mediated cascade was initiated by carbonyl addition to the alkyne moiety. The resulting 1,4- or 1,3-dipoles could then participate to formal [4 + 2] and [3 + 2] cycloadditions with an olefinic partner, giving access to... 

Zhang and co vorkers reported a number of cycloaddition reactions, somewhat related to enyne cycloisomerization, in which a gold-mediated cascade was initiated by the addition of a carbonyl moiety onto an alkyne. Furans and thiophenes were also found to react with alkynes in an intra- or intermolecular manner in the presence of an NHC-gold catalyst to generate complex structures. 

Zhang, L., Sun, J. and Kozmin, S.A. (2006) Gold and platinum catalysis of enyne cycloisomerization. Advanced Synthesis Catalysis, 348, 2271-2296. Khramchikhin, V.A., Dogadina, A.V., Khramchikhin, A.V. and lonin, B.I. (2012) Heterocyclization reaction of chloroacetylenephosphonates with 2-acylamidomalonates into 5-(dialkoxyphosphorylmethylidene)oxazolines. Russian Journal of General Chemistry, 82(4), 776-778 Zhurnal Obshchei Khimii, 82(4), 694-696. 

Cao P, Zhang X (2000) The first highly enantioselective Rh-catalyzed enyne cycloisomerization. Angew Chem Int Ed 39 4104-4106... 

Zhang54 published the first and only account of a non-asymmetric rhodium-catalyzed Alder-ene cycloisomerization of 1,6-enynes.55 The conditions developed by Zhang and co-workers are advantageous in that, similar to the ruthenium conditions developed by Trost, selectivity for 1,4-diene products is exhibited. The rhodium conditions are dissimilar from many other transition metal conditions in that only (Z)-olefins give cycloisomerization products. 

Rh(III)-metallocydes derived from 1,6-enynes are postulated as reactive intermediates in catalytic [4+2] and [5+2] cycloadditions, Pauson-Khand reactions and cycloisomerizations P. Cao, B. Wang, X. Zhang, J. Am. Chem. Soc. 2000, 122, 64901 and references cited therein. 

One of the major advantages of the rhodium(I)-catalyzed Alder-ene reaction is that mild conditions are used to effect the cycloisomerization process thus increasing the likelihood of being able to facilitate an asymmetric reaction. In fact, Zhang has demonstrated convincingly that the Alder-ene reaction of enynes can indeed be performed with excellent enantioselectivity and with similar efficiency. These examples are highlighted below in chronological order. 

Moreover, in Zhang s systems cycloisomerization of an unprotected secondary amide in the enyne Alder-ene reachon was not possible. 

In later work, Zhang also examined the reactivity of ether substrates with additional substituents at the allylic position (Fig. 10.19) [32] and demonstrated that an highly effective kinetic resolution process takes place in the presence of rhodium/BINAP catalysts. In these cycloisomerization processes, the initial kinetic resolution coupled with a diastereoselective cyclization step allow the synthesis of tetrahydrofurans with two adjacent stereogenic centres, with excellent e.e. and conversion rates. In the representative reaction shown in Fig. 10.19, the 5-configured BINAP matches the 2/ -configured enyne substrate which is thus quantitatively converted into the expected tetrahydrofurane. The 25 -configured substrate remains unchanged. 

Excellent enantiomeric excesses have been obtained by Zhang et al. also in the synthesis of cyclopentanes and cyclopentanones via cycloisomerization of carbon-tethered enynes promoted by the same cationic Rh/BINAP catalysts (Fig. 10.23) [35]. These stmctures had been targeted most particularly since they are useful building blocks for the construction of biologically active molecules and industrially relevant compounds such as prostaglandins and jasmonates. Actually, enantiomerically pure (i5,25)-dihydrojasmonate could be prepared indeed by this elegant methodology. 

Lei A, Waldkirch JP, He M, Zhang X (2002) Highly enantioselective cycloisomerization of enynes catalyzed by rhodium for the preparation of functionalized lactams. Angew Chem Int Ed 41 4526-4529... 

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