Intramolecular, addition pinacol coupling

By choosing an appropriate titanium complex, a /ra r-isomer of 1,2-cyclohexanols can be prepared selectively. Because intramolecular pinacol coupling of hexanedials with Sml2 usually produces t-isomers of cyclohexane-1,2-diols, the titanium-mediated reaction complements the samarium-mediated cyclization (Equation (17)). In addition, when a /-butyl group fixes the conformation of the substrate, one of the diastereomers is produced selectively (Equation (18)). ... 

The CHDs formed by intramolecular addition often eliminate water to give another of,)6-unsaturated ketone. For mesityl oxide (4-methyl-3-pentene-2-one), 22b, the influence of the reaction conditions on the product distribution was examined in detail [96]. Mixtures of four dimeric species were observed, resulting from initial 4,4 -coupling (24b-d), or from mixed 2,4 -coupling, 24a. Pinacol formation (2,2 -coupling) was not observed [Eq. (6)]. 

Related to the intramolecular pinacolic coupling reactions in some respects is a ketone-nitrile reductive coupling process. This process also permits the construction of highly functionalized carbocycles, although the yields are sranewhat reduced owing to the reluctance of nitriles to undergo such radical addition reactions (equation 75). Presumably, simple reduction of the ketone to the alcohol c< npetes with the desired process. 

Palominol. Corey has reported the application of an intramolecular titanium-mediated pinacol coupling reaction to the synthesis of a 15-membered ring, en route to palominol, a marine diterpenoid that displays cytotoxicity toward the human colon cell line (Eq. 3.10) [28]. Slow addition of the keto aldehyde (32 h) to the titanium reagent furnished the cyclized product in 53% yield as a mixture of diastereomers (2.1 1). 

Radically induced coupling of two t-systems also provides a synthetically useful route to cyclohexanes. The 6-endo-tng cyclization of the vinyl radical generated by Bu3Sn radical addition to the carbohydrate alkyne 147 provided a novel route to carbasugar 148 [93]. The intramolecular pinacol coupling of 1,6-dicarbonyl compounds such as 149 provides a direct synthesis of the inositol 150 [94] (Scheme 24). 

A monoprotected pinacol can be obtained in 81% yield by intramolecular coupling of 2,2 -biaryldicarbaldehyde mono-dibenzyloxy acetal, using samarium(ii) iodide in THF in the presence of BF3-OEt2 (Equation (47)). As in the case of homocoupling of 2,2 -biaryldicarbaldehyde, the /ra r-isomer is produced selectively. Addition of the Lewis acid is important to obtain high yields, otherwise the yield drops to 37%. ... 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

Previously, tin-ketyl radicals have been added to alkenes only in an intramolecular fashion. [9] In recent publications, however, pinacols and amino alcohols have been prepared by cyclisation of dicarbonyl compounds [10] or keto-oximes [11] with tributyltin hydride. Cyclisation of 1,5-ketoaldehydes 1 and 1,5-dialdehydes with tributyltin hydride yields cw-diols 2 with excellent stereoselectivities, whereas the keto-oxime 4 with four benzyloxy-substituents affords a 58 42 cis trans) mixture. The tran -product was transformed in two more steps to the potent glycosidase inhibitor 1-deoxynojirimycin (6). [lib] The reversibility of both the addition of the tributyltin-radical to the carbonyl group and the intramolecular radical C-C bond formation is believed to be responsible for the high selectivity in the formation of 2. In the cyclisation of 1,5-pentanedial the unhydrolyzed coupling product 3 could be isolated, therefore providing evidence for a new mechanistic variant of the pinacol reaction, in which only 1.2 equivalent of the reducing agent are necessary. 

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