Rings, bicyclic, stereoselectivity reactions

The electrophile-promoted cyclization in cyclic systems is a highly regio- and stereoselective reaction that can be carried out under various conditions and with a range of electrophiles. The bicyclic lactone products have the cfs-ring fusion, indicating that the electrophile approaches from the face of the molecule anti to the carboxyalkyl side chain. Such halolactonizations constitute a useful approach to bicyclic and polycyclic compounds. 

We have just looked at the way the reactivity of an epoxide gains additional subtleties when it is fused into a bicyclic structure with a six-membered ring. We re now going to look more generally at bicyclic compounds and their reactivity, and consider some features of their stereoselective reactions. 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

A series of bicyclo[3.3.0]octanols are accessible by electroreductive tandem cyclization of linear allyl pentenyl ketones 189, as shown by Kariv-Miller et al. [189]. The electrolyses are carried out with an Hg-pool cathode and a Pt-flag anode. As electrolyte, tetrabutylammonium tetrafluororborate is used. The reaction is stereoselective, yielding only two isomers 192 and 193. In a competing reaction, a small amount of the monocyclic alcohol is formed. Since all the monocycles have the 1-allyl and the 2-methyl group in trans geometry it is assumed that this terminates the reaction. The formation of a bicyclic product requires that the first cyclization provides the cis radical anion which leads to cis-ring juncture [190] (Scheme 37). 

The reaction with monomethyl malonate in acetic acid, which does not occur at 0-10°C, proceeds smoothly when sonication is applied (Allegretti et al. 1993). From cyclohexene, only the cis ring fusion in bicyclic lactone is observed the product is formed at 80% yield for 15 min at 10°C. The overall transformation, in brief, is shown in Scheme 6.16. The stereoselectivity of the sonochemical process probably reflects the enhanced reaction rate, which does not allow equilibration processes to take place. 

A possible mechanism that features a six-membered transition state is given in Scheme 18 (38, 43). The high catalytic activity stems from the excess strain of the B=N bond in the 5/5-fused bicyclic ring system, which results in strong coordination of the angular nitrogen atom to BH3 to form the active dinuclear species. The rate and stereoselectivities of the reaction of trihalomethyl ketones has been explained on the basis of the X-ray analysis of the substrates. 

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