Gold-catalyzed cyclopropanation

An enantioselective version of the gold-catalyzed cyclopropanation was reported by Michelet and co-workers. In the presence of [Au2 (/ )-3,5-/-Bu-4-MeO-MeOBIPHEP Cl2] and AgOTf, 3-oxabicyclo[4.1.0]hept-4-ene derivatives were obtained with excellent enantioselectivities (Scheme 4-26). Both electron-rich and electron-poor aryl groups are tolerated under these conditions. Lower reactivities and stereoselectivities were observed in the corresponding platinum- or iliodium-catalyzed cycloisomerizations. ... 

P. Chen Gas-phase synthesis and reactivity of a gold carbene complex a gold benzylidene complex ion was observed, corresponding to the presumed reactive intermediates of a gold-catalyzed cyclopropanation reaction. [220]... 

Nevertheless, the earbene rendition remains popular because it represents in the chemist s mind a relevant intermediate in reactions such as electrophilic cyclopropanation or [l,2]-sigmatropic shifts. In that respect, Toste showed that the yield of the gold-catalyzed cyclopropanation of cis-stilbene 115 with cyclopropene 114 was critically dependent on the ancillary ligand L on Au (Scheme 4.32). For instance, the use of phosphite ligands such as P(OMe)3 and P(OPh)3 led to poor yields. In the case of phosphines, which are less n-acidic than phosphites, the desired cyclopropane 116 was obtained with moderate yields. On the other hand, the use of IPr, which is strongly o-donat-ing and weakly n-acidic compared with a phosphite, provided 116 in 80% yield. 

In the carbene insertions to alkane C-H bonds the same concept as for the olefin cyclopropanations is applied. In that work, the gold-catalyzed carbene transfer is now used for insertions into C-H bonds (equation 150), with a selectivity that is influenced by the electronic properties of the ligand and the counterion employed. The carbene and nitrene insertion is not limited to Csp H bonds, but N H (equation 151), O H (equation 152), and aryl Csp -H bonds react as well (equation 153). ... 

The gold-catalyzed intramolecular cyclopropanation can also be performed with allyl propargyl ethers that are prepared by substitution of allyl acetates with propargyl alcohols. These steps can be combined in a tandem s3mthesis of 3-oxabicyclo[4.1.0]hept-4-ene derivatives using Ph3PAuNTf2 as catalyst for both steps. The products were obtained as a single diastereomer. 

General procedure for the gold-catalyzed intermolecular cyclopropanation of 1,6-enynes with alkenes... 

There are many examples of preparing cyclopentane structures from enynes by gold-catalyzed carbocyclization reactions. Toste et al. have reported that Au(l)-phosphine complexes act as superior catalysts for isomerization of 1,5-enynes to bicyclo[3.1.0]hexenes [124]. For example, treatment of 1,5-enyne (86) with 1 mol% of PhsP-AuPFfi in dichloromethane at room temperature results in formation of cyclopropane-fused cyclopentene (87) in 99% yield (Scheme 18.30). 1,6-Enynes also undergo similar cycloisomerization to five-membered cyclic compounds under the influence of cationic gold(l) catalysts [125, 126], Hydroxylated enynes are versatile precursors for cyclopentenones by gold-catalyzed cycloisomerization... 

The next step toward the completion of the preparation of Lundurine A would involve the synthesis of alkynylindole XVII and the subsequent cyclization via a gold-catalyzed reaction. The intermediate reactions have already been identified and optimized on a model system. The key steps in the synthesis will be the conversion of alkynylindole XVII into XVIII and a subsequent intramolecular cyclopropanation to obtain Lunderine A [16-26]. 

In gold catalyzed transformations, the carbenoid intermediates such as 31 arising from a 5-exo-dig cyclization can also be either oxidized in the presence of Ph2SO leading to carbaldehyde 32 or trapped by an alkene to give bis-cyclopropanic derivatives 33 (Scheme 5.12) [55-57]. 

Scheme 4.32 Au-catalyzed cyclopropanation of cfs-stilbene 115 with cyclopropene 114 via gold carbenoids of type 117.

Alkenylboron compounds cyclopropanations, 9, 181 haloetherification, 9, 182 hydrogenation and epoxidation, 9, 182 metal-catalyzed reactions, 9, 183 metallic reagent additions, 9, 182 via radical addition reactions, 9, 183 5-Alkenylboron compounds, cross-coupling reactions, 9, 208 Alkenyl complexes with cobalt, 7, 51 with copper, 2, 160, 2, 174 with Cp Re(CO) (alkene)3 , 5, 915-916 with dicarbonyl(cyclopentadienyl)hydridoirons, 6, 175 with gold, 2, 255... 

The easiest reactions are those in which the nucleophile is the gold-activated species. Examples of this are Au(I)-catalyzed carbene and nitrene transfers (equations 142 and 143) that convert olefins into cyclopropanes or aziridines, respectively. In the carbene transfer, ethyl diazoacetate is the source of carbene and the active NHC-gold cationic catalyst is generated by chloride abstraction with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate NaBAT4. The cyclopropanation is competitive with other carbene insertions with active C H or N H bonds present in the substrate. For the aziridinations of olefins, nitrene formation is accomplished by the oxidation of sulfonamides with PhI(OAc)2 and the catalyst of choice is a gold-(I) triflate with a terpyridine ligand. 

Lundurine A could be synthesized from indoloazocine TTT-12 after cycloprop-anation of the indole ring. The intermediate III-12 would be formed by gold(III)-catalyzed cyclization of the alkynylindole ni-13, (See Ref. [118] and [133] in Chap. 1) which arises from III-14 upon conversion of the ester group into a homologated alkyne." Compound III-14 would be assembled from an enantiome-rically pure pyroglutamic ester derivative III-16 and an indole derivative III-15. Two approaches were considered for the cyclopropanation reaction from TTT-12 derivatives (Scheme 4.12) the intermolecular (A) and intramolecular (B). 

Nieto-Oberhuber, C., Lopez, S., Munoz, M. R, Jimenez-Nunez, E., Bunuel, E., Cardenas, D. J., Echavarren, A. M. (2006). Gold(I)-catalyzed intramolecular cyclopropanation of dienynes. Chemistry - A European Journal, 12, 1694-1702. 

Johansson, M., Gorin, D., Staben, S., Toste, F. (2005). Gold(I)-catalyzed stereoselective olefin cyclopropanation. Journal of the American Chemical Society, 127, 18002-18003. 

Lemibre, G., Gandon, V., Cariou, K., Fukuyama, T., Dhimane, A.-L., Fensterbank, L., Malacria, M. (2007). Tandem gold(I)-catalyzed cychzation/electrophilic cyclopropanation of vinyl allenes. Organic Letters, 9, 2207-2209. 

Miscellaneous Gold- and Iron-Catalyzed Cascade Reactions The car-benic reactivity of gold catalysis was exploited toward the synthesis of stereoselective six-membered ring carbocycles, through cyclopropanation reactions incorporated in cascade sequences [31]. 

Benzonorcaradine derivatives have been synthesized by [4 - - 3] annotation from propargyl ester-containing dienes and styrenes (Scheme 18.22) [21]. This synthesis involves a cationic gold(I)-catalyzed tandem cyclopropanation/hydroarylation reaction. 

Gold complexes are the most useful catalyst for the cyclo-propanation reaction. A recent minireview is available [218]. Toste and coworkers reported that a gold complex catalyzed the intramolecular cyclopropanation of enyne compounds... 

This type of cyclopropanation reaction catalyzed by a gold(I) complex produced cyclopropylmethyl carbene complex 321, which is reactive toward external alkenes or nucleophiles. The reaction depended on the ligand of the gold complex as well as the substituted patterns of enyne compounds. Echavarren and coworkers reported a cyclopropanation reaction mechanism. The cyclopropane gold complex intermediates 322 and 323 were trapped by external alkenes to give cyclopropanes 324 and 325, respectively (Scheme 1.157) [227]. 

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