Ring with simultaneous synthesis

An example, where two C-C-bonds are formed and one C-C-bond is broken is the synthesis of the tricycle 3-285, which has some similarity with the eudesmane framework 3-286, developed by Kilburn and coworkers (Scheme 3.72) [113]. Thus, exposure of the easily accessible methylenecyclopropyl-cyclohexanone 3-281 to samarium(II) iodide led to the generation of ketyl radical 3-282, which builds up a six-membered ring system with simultaneous opening of the cyclopropane moiety. Subsequent capture of the formed radical 3-283 by the adjacent alkyne group afforded the tricycle 3-285 via 3-284 as a single diastereoisomer in up to 60% yield. It should be noted that in this case the usual necessary addition of HMPA could be omitted. 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

Introduction of arylsulfonylmethyl substituents into nitroheteroaromatic rings is of great practical value because these sulfones are versatile intermediates in organic synthesis. Nitrobenzyl aryl sulfones and their heterocyclic analogues can easily be transformed into the corresponding ethenyl derivatives by a simple alkylation with simultaneous elimination of arylsulfinate anion [125]. Diethyl methylenemalonate substituent can be introduced in the positimi 4- of 5-nitroimidazole via the VNS reaction of 5-nitroimidazole with the carbanion of chloromethyl phenyl sulfone [112, 124], followed by condensation of the obtained 4-(phenylsulfonyl)methyl derivative with diethyl bromomalonate or diethyl ketomalonate (Scheme 33) [126]. 

Synthesis from l,2-Dithiole 3-thiones. 5-Aryl-l,2-dithiole-3-thiones (118) react with a-chlorobenzylidenephenylhydrazine (119), with simultaneous dithiole-ring opening and formation of (A -l,3,4-thiadiazolin-2-ylidine)-thioacetophenones (120). The use of ethyl bromo(phenylhydrazono)-acetate similarly affords (5-ethoxycarbonyl-3-phenyl-A -l,3,4-thiadiazolin-2-ylidene)thioacetophenone, which is saponifiable to the corresponding 5-carboxylic acid. The reactions resemble Huisgen s synthesis of iV-(3,5-diphenyl-A -l, 3,4-thiadiazolin-2-ylidene)benzamide from (119). 

Fabbrizzi developed receptor 45 that is able to bind L-His, with log K = 5.5, in aqueous solution, and rationalized this behavior by the simultaneous coordination of the imidazole of L-His to both Cu(II) centers of the receptor. A further development was reported by the same group two years later with the synthesis of a binuclear Zn complex of an anthracenic ligand (46) for the recognition of L-His (log K = 2.92) (Figure 19). This receptor is also a fluorescent chemosensor for this amino acid, provided the imidazole ring acts both as a coordinating bridge between two zinc centers and as a quencher of the anthracenic fluorescence (via PET). 

Apart from metallic salts, simultaneous chemical synthesis and doping of polypyrrole has been achieved by an halogenic electron acceptor, as bromine or iodine, in several solvents [27-31]. Both PPy-l2 and PPy-Br2 complexes have conductivities in the order of 1 to 30 S cm [30]. PPy-Cl2 prepared polymers have conductivities from 10 to 0.5 S cm [27]. The loss of conductivity with respect to PPy-Br2 or PPy-h has been associated with a partial chloration of the pyrrole ring, with some loss of conjugation. Both PPy-l2 and PPy-Br2 complexes show a good stability upon repeated redox cycling in both aqueous and organic electrolytes [31]. 

Cyanohydrin Synthesis from Osones (14 )- For this method, 3-keto aldonic acids are formed as intermediates which are not isolated. The first product, the nitrile, immediately enolizes with simultaneous ring formation to an imino analog (XI) of the ascorbic acid, and the latter is formed by... 

Vollhardt s total synthesis of strychnine successfully demonstrated the power of the cobalt-mediated [2+2+2]cycloaddition (111) for the construction of complex polycyclic molecules (Scheme 11). This key reaction was originally developed by his group in the 1970s, and widely utilized for the syntheses of complex natural and unnatural products (112-116). Here, this reaction was used for the simultaneous closure of the E and G rings with formation of the C7 quaternary center (117-119). To accomplish total synthesis, five synthetic approaches were investigated, but only the successful one is shown here. 

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