Cyclization quaternary carbon center formation

Catalyst 70 is very effective for the reaction of terminal alkenes, however 1,1-disubstituted olefins provide hydrosilylation products presumably, this is due to steric hindrance [45]. When a catalyst with an open geometry (78 or 79) is employed, 1,1-disubstituted alkenes are inserted into C-Y bonds to give quaternary carbon centers with high diastereoselectivities (Scheme 18). As before, initial insertion into the less hindered alkene is followed by cyclic insertion into the more hindered alkene (entry 1) [45]. Catalyst 79 is more active than is 78, operating with shorter reaction times (entries 2 and 3) and reduced temperatures. Transannular cyclization was possible in moderate yield (entry 4), as was formation of spirocyclic or propellane products... 

Two sequential electrochemical annulations of an electron-rich 3,4-disubstituted furan ring were employed to generate the fused tricyclic ring system of arteannuins. The second reaction, as depicted below, represented the formation of a quaternary carbon center by a formal 6-endo cyclization under these anodic oxidation conditions <07OL4599>. 

From the preliminary studies with simple model compounds, it is clear that the consecutive carbon-carbon bond formation approach, via radical cyclization of )V-aziridinylimines, represents a highly efficient strategy for the construction of quaternary carbon centers. 

A pentalenene skeleton contains three rings and a quaternary carbon center at the ring junction. Since the carbonyl carbon would be converted into the quaternary carbon in the present approach, two of four carbon-carbon bonds at the quaternary carbon center can be formed by radical cyclization via the consecutive carbon-carbon bond formation approach. As shown in Figure 10, two of the four bonds at the quaternary carbon center may be disconnected and any one of the three rings can be selected as the central ring, as indicated by the dotted... 

Scheme 20. Polyene cyclization mediated by transition metals with formation of quaternary carbon centers...

Although only a few examples have been reported for the consecutive carbon-carbon bond formation approach in cyclization reactions [30], A-aziridinylimines are ideally suited for the construction of quaternary carbon centers. Based on the consecutive carbon-carbon bond formation approach, several sesquiterpenes (Fig. 2) have been synthesized. In order to demonstrate how to execute the synthesis using the consecutive carbon-carbon bond formation approach, the synthesis of DL-zizaene is discussed [31]. 

In the enantioselective synthesis of a cardenolide precursor, the congested quaternary carbon center and the cw-AB ring fusion in the steroid skeleton 224 were constructed by cyclization of the alkenyl triflate 223 [102]. Similarly critical quaternary carbon-aryl bond formation took place by the cyclization of the bromopyridine 225 to afford the pyridinomorphinan 226 using 60 mol% Pd triflu-oroacetate and PPhs [103]. 

This work presents the first catalytic enantioselective cyclization strategy for accessing steroidal and terpenoidal frameworks using organocatalysis. It should be pointed out that the present domino cycHzation could be conducted at room temperature. The asymmetric construction of multiple C-C bonds and contiguous stereocenters using substrate 263 in the presence of the chiral imidazolidinone 259 resulted in the formation of 264 with four new C-C bonds, seven stereogenic centers, and three quaternary carbon centers with about 90% yield for each chemical bond formation and over 90% ee. 

Zr-catalyzed enantio-selective intramolecular diene cyclizations with allylic alcohol and ether substrates afford carbocycles bearing quaternary carbon stereogenic centers the unexpected formation of the aldehyde product 19 is noteworthy. 

Related substrates were repeatedly cyclized in an enantioselective fashion. t i For these examples the formation of a quaternary carbon as the chiral center is crucial. Very often BINAP has been applied as the chiral ligand the synthesis of the chiral aldehyde in Scheme 6 represents an important step in the synthesis of physostigmine.f " ... 

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