Cycloisomerization regioselectivity

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... 

Very recently, Leitner has reported cationic nickel(n) catalyst systems for the cycloisomerization of diethyl diallyl malonate that shows high activities and regioselectivities for the formation of diethyl 3-methylene-4-methylcyclo-pentane-l,l-dicarboxylate with ee values up to 80% when using Wilke s azaphospholene ligand.355... 

Gycloisomerization of a disubstituted alkyne sometimes required activation of the alkyne by the addition of a conjugated carbonyl and performing the reaction at a higher temperature as in Equation (38). The geometry of the alkene determines the regioselectivity of the /3-hydride elimination, as ( )-60 gave predominantly 61 (Equation (38)), while 62 was the major product of the cycloisomerization of (Z)-60 (Equation (39)). 

Another focus of this chapter is the alkynol cycloisomerization mediated by Group 6 metal complexes. Experimental and theoretical studies showed that both exo- and endo- cycloisomerization are feasible. The cycloisomerization involves not only alkyne-to-vinylidene tautomerization but alo proton transfer steps. Therefore, the theoretical studies demonstrated that the solvent effect played a crucial role in determining the regioselectivity of cycloisomerization products. [2 + 2] cycloaddition of the metal vinylidene C=C bond in a ruthenium complex with the C=C bond of a vinyl group, together with the implication in metathesis reactions, was discussed. In addition, [2 + 2] cycloaddition of titanocene vinylidene with different unsaturated molecules was also briefly discussed. 

Chiral carbo- and heterocycles are widespread structural motifs in biologically active compounds. The cycloisomerization of 1,6-dienes (A) offers an elegant and atom-economic [56] approach to five- or six-membered carbo- or heterocycles [57]. Metal complexes based on Pd [58], Ni [59], Rh [60], Ru[61], and Ti[62] have been identified as promising lead structures for catalyst development. Some of the reported systems are highly chemo- and regioselective toward the formation of the individual five-membered ring compounds B-D (Scheme 2.1.5.2). Enantioselec-tive cycloisomerization, however, has been assessed only sparsely so far, and remains a challenging task [46, 63]. 

Van der Eycken s group developed a silver(I)-mediated synthesis of substituted furo[2,3-6]pyrazines.53 Starting from -methoxybenzyl-protected 3,5-dichloropyr-azine-2(l//)-ones 26 (Scheme 5.13), after a regioselective microwave-assisted Sonogashira reaction with various terminal alkynes, the cycloisomerization reaction could occur using AgOTf (2 mol%) with trifluoroacetic acid (TFA, 5 equiv) to yield... 

In contrast to these intermolecular enone + alkene photocycloadditions, the regioselectivity in the corresponding intramolecular cycloisomerizations of alkenylcycloalkenones is controlled primarily by... 

High chemo- and regioselectivity were observed for the metal complex-catalyzed cycloisomerization of readily available 4-propargyl-cyclohexanediones, leading to the formation of fused oxabicycles. As can be seen in the reactions below, a proper choice of metal catalyst can provide the 2-alkylidenetetrahydrofuran almost exclusively . 

In the case of the cyclic substrate 51, the intervention of a C-H insertion pathway reveals itself in terms of the diastereoselectivity, not regioselectivity. Thus, exposure of enyne 51 to the standard Ru catalyst at ambient temperature produced the transfused bicyclo[5.4.0]undecene 52 (Equation 1.60, path a) [55]. If a metallacycle mechanism was operative, coordination of the metal with both the alkene and alkyne must occur to form the cis-fused product. On the other hand, coordination of the Ru with the Lewis basic bridgehead substituent directs it to abstract an allylic C-H on the same face as the substituent, which then leads to the trans-fused product as observed. On the other hand, cycloisomerization using a Pd(0) precatalyst does indeed lead to the Z-fused bicycle (Equation 1.60, path b). 

Trost, B.M., Jean-Philippe Surivet, J.-P. and Toste, F.D. (2004) Ruthenium-catalyzed enyne cycloisomerizations. Effect of allylic silyl ether on regioselectivity. Journal of the American Chemical Society, 126, 15592-15602. 

An example of palladium-catalyzed furan synthesis utilizing allenes as starting materials was reported, in which 2,4-disubstituted-2,3-butadienoic acids and 1,2-propadienyl ketones were used and 2,4-disubstituted furans were produced. The reaction may proceed via a matched double oxypalladation-reductive elimination process <04CEJ2078>. In a similar cycloisomerization of substituted allenes to tri- and tetrasubstituted furans with regioselectivity, the allenes were produced in situ from acyloxy-, phosphatyloxy- and sulfonyloxy-substituted alkynylketones via a 1,2-migration of such substituents catalyzed by CuCl or AgBF <04AG(E)2280>. 

Cycloisomerizations. 1,6-Enynes and 1,7- analogues cyclize to furnish 2-vinyl-l-methylenecycloalkanes in the presence of [CpRu(MeCN)3]PFf . The regioselectivity is contrary to that catalyzed by Pd-catalysts. 

Substituted and 3-substituted 4H-furo[3,2-c]chromenes were synthesized using a new class of cyclopropenes containing a chroman-4-one motif by cycloisomerization. When using BF3-Et20 as catalyst, 2-substituted 4H-furo[3,2-c]chromene was exclusively obtained in 70% yield. On the other hand, 3-substituted 4H-furo[3,2-c]chromene was obtained in 95% yield with 98 2 regioselectivity when Cu(OTf)2 was used as catalyst (140L5524). 

The solvent effect on the regioselectivity of the AuCls-catalyzed cycloisomerization of a bromoallenyl ketone was evaluated by density functional theory calculations. Upon the generation of the gold carbenoid intermediate from cyclization of the aUene precursor, the tetrahydrofiiran solvent can act as a proton shuttle to assist the 1,2-H migration to afford the 2-bromofuran product (14S2149). 

A regioselective transition metal-catalyzed cycloisomerization reaction of boron-containing alkynyl epoxides toward C-2- and C-3-borylated furans was developed. It was found that the copper catalyst as well as the gold catalyst with a relatively more basic triflate counterion favored boryl migration toward C-3-borylated furans, whereas employment of the cationic gold hexafluoroantimonate afforded C-2-borylated furans via a formal 1,2-hydrogen shift (14JA13146). 

Ashfeld et al. expanded the scope of this Rh-catalyzed domino reaction to other types of cycloadditions. It was reported that [Rh(CO)2Cl]2 was an effective catalyst for allylic alkylation with high regioselectivity. When an enantiomerically pure carbonate was employed, the allylic alkylation gave the product with retention of absolute configuration (98% ee). In addition to studying allylic alkylation reactions, a series of novel domino reactions such as cycloisomerizations and [5+2] cycloadditions was explored (Scheme 2-93). ... 

Ph3PAuNTf2 catalyses the regioselective cycloisomerization of substituted aryl propargyl ethers into 2//-chromenes (Scheme 119). ... 

An efficient and one-pot synthesis of multisubstituted pyrroles with high diversity and in a regioselective manner from the reactions of suitably substituted (Z)-enynols with amines or sulfonamides under mild reaction conditions has been developed (Lu et al. 2009). This synthesis was realized via a cascade process in the presence of gold/ silver (Au/Ag) or boron trifluoride etherate/gold/silver (BFj EtjO/Au/Ag) catalysts, which could catalyze amination and cycloisomerization reactions in the same vessel. Scheme 11.2 illustrates that either silver trifluoromethanesuUbnale or a mixture of... 

Later, Padwa reported a regioselective Rh(II)-catalyzed room temperature cycloisomerization of trisubstituted cyclopropenyl ketones to give 2,3,4-trisubstituted... 

Aiming for the development of transition metal-catalyzed protocols, which would allow a regioselective synthesis of C2-substituted indolizine cores, Gevorgyan reported a highly efficient Au(III)-catalyzed cascade cycloisomerization of skipped propargylpyridines 346 into indolizines 347 (Scheme 9.119) [299,300]. This cascade transformation involved a facile 1,2-migration of silyl-, stannyl-, and even germyl... 

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