Regiodirecting effects

The cyclization of the homologous epoxide 36 under acidic conditions was also investigated (Table 9.5) [110]. As would be expected, compound 36a reacted by a 6-exo cyclization to give tetrahydropyran 38a (Entry 1). The a, 3-unsaturated hydroxy epoxide 36b gave a 1 3.5 mixture of oxepane 37b and tetrahydropyran 38b (Entry 2). Subjection of 36c and 36d, which both contain more electron-rich 71-systems, to the reaction conditions resulted in preferential 7-endo cyclization to give 37c and 37d, thus confirming the powerful regiodirecting effect of the vinyl moiety (Entries 3 and 4). 

The total synthesis of the carbazomycins emphasizes the utility of the iron-mediated synthesis for the construction of highly substituted carbazole derivatives. The reaction of the complex salts 6a and 6b with the arylamine 20 leads to the iron complexes 21, which prior to oxidative cyclization have to be protected by chemoselective 0-acetylation to 22 (Scheme 13). Oxidation with very active manganese dioxide followed by ester cleavage provides carbazomycin B 23a [93] and carbazomycin C 23b [94]. The regioselectivity of the cyclization of complex 22b to a 6-methoxycarbazole is rationalized by previous results from deuterium labeling studies [87] and the regiodirecting effect of the 2-methoxy substituent of the intermediate tricarbonyliron-coordinated cyclo-hexadienylium ion [79c, 79d]. Starting from the appropriate arylamine, the same sequence of reactions has been applied to the total synthesis of carbazomycin E (carbazomycinal) [95]. 

Scheme 4.38 Regiodirecting effects in the hydroformylation of allyl amides and possible side reactions.

The hydrogenation activity of the intermediate rhodium complex was lowered by the use of the corresponding unsaturated phosphites as substrates, although the pressure had to be increased to 34bar (Scheme 4.105) [11]. Alcohols yielded only by separate reduction of the aldehydes with LIAIH. The dominance for the formation of the branched aldehyde was not affected by branching ofthe substrate. Increasing the distance between phosphite and olefin caused the total loss of the regiodirecting effect. 

Regiodirecting Effects without the Establishment of Covalent Interactions... 

In contrast to their effect of rhodium-catalyzed hydroformylation, organic ligands effect on the cobalt-catalyzed reaction is less pronounced. Moreover, a desired regiodirecting effect strongly depends on the equilibrium between the modified and unmodified catalyst. 

For discussion of synthesis design based on the manipulation of competing regiodirecting effects, see [4] this same concept has been discussed in terms of matched and mismatched pairs of substituents (see [5]), by an extension of the nomenclature used for double stereodifferentiation, but since double stereodifferentiation effects can arise... 

The classic rf cyclohexadienyl complexes of Fe(CO)3 first investigated by Fischer and Fischer [56], and subsequently by many research groups (including my own) provide a wealth of examples of studies of regiodirecting effects of substituents. With simple alkyl groups, steric effects send the nucleophile to the co position... 

---