Pinacol coupling reactions intramolecular

Not many catalyzed processes involving free radicals are known with these metals. Some vanadium-catalyzed pinacol coupling reactions were developed (reviews [129, 171], [172, 173] and cited ref, [174]). Niobium and tantalum complexes were applied in pinacol coupling reactions [130]. Vanadium(IV) [175-179] and vanadium(V) ([129], reviews [180-186]) complexes are known to catalyze asymmetric oxidative dimerizations of phenols and naphthols in moderate to excellent ees applying oxygen as the terminal oxidant. Biaryls are accessible by intramolecular coupling of sodium tetraarylborates, catalyzed by EtOVOCl2 in the presence of air [187]. 

The use of this protocol provided good to excellent diastereoselectivities in a range of intermolecular and intramolecular pinacol coupling reactions. 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

The Sml2-mediated intramolecular pinacol coupling reactions of carbonyls 151 were found to afford heterocyclic diols 152 in diastereoselective... 

Intramolecular pinacol coupling reactions are known, giving cyclic 1,2-diols. Dialdehydes have been cyclized by reaction with TiCls to give cyclic 1,2-diols in good yield. ° A radical-induced coupling of an a,03-dialdehyde led to cw-l,2-cyclo-pentanediol when treated with BuaSnH and AIBN. or induced photochemically. ... 

Curiously, the relative stereochemistry between the carboxylate and the adjacent hydroxy group in the Sml2-mediated intramolecular pinacolic coupling reaction is opposite to that observed in the intramolecular Barbier reactions and ketone-alkene reductive coupling reactions discussed previously (compare... 

In a useful extension of the methodology, highly functionalized noniacemic carbocycles can be synthesized by intramolecular pinacolic coupling reactions utilizing readily available oxazolidinone precursors (equation 74). ... 

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. 

Intramolecular pinacolic coupling reactions have also proven successful with Stnl2. Yields with simple diketones are relatively low. i> However, excellent yields and diastereoselectivities are achieved in intramolecular pinacolic coupling reactions of P-keto ester and P-ketoamide substrates (equation 72). A variety of substitution patterns can be tolerated in these reactions to generate five-membered carbo-cycles. Six-membered rings can also be generated by this process, but substantially lower yields and diastereoselectivities are observed (equation 73). Yields obtained for p-ketoamide substrates are also lower than those observed in the P-keto ester series. 

Rocaglamide. Taylor has employed an intramolecular keto-aldehyde pinacol coupling reaction in a synthesis of rocaglamide, an anti-leukemia natural product (Eq. 3.4) [20]. Other reducing agents were either completely ineffective (e.g., Zn/ TMSCl and Zn/TiCU) or significantly less efficient (e.g., Mg/Hg/TiCU and LiAlHVCpTiCls) than Smli. 

L-C/tiVo-inositol. Chiara has reported a synthesis of L-c/nVo-inositol from D-sorbi-tol that employed a highly stereoselective intramolecular pinacol coupling reaction as the key step (Eq. 3.5) [21]. Thus, treatment of the illustrated dialdehyde with Sml2 afforded the desired diastereomer with 94 6 stereoselection (neither of the other two diastereomers was detected) in >78% yield. The major reaction product was the one expected based upon previous studies of Sml2-mediated pinacol cy-clizations [22]. 

Forskolin. Prange has described a formal total synthesis of forskolin, a diteipe-noid that serves as an activator of adenylate cyclase, in which an intramolecular Sml2-mediated pinacol coupling reaction was a pivotal transformation (Eq. 3.6) [23]. Only the desired diastereomer was produced in this 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). 

By contrast, the intramolecular version of the reaction is considerably more useful, and a wide range of substrates have been successfully coupled. The first reasonably general survey of SmE-promoted intramolecular pinacolic coupling reactions... 

The utility of SmE-promoted intramolecular pinacolic coupling reactions of dialdehydes was nicely demonstrated in the key step of one synthesis of the natural product forskolin (Eq. 28) [38]. 

In analogy to intermolecular pinacolic coupling reactions, organometallic dialdehydes have served as precursors for the intramolecular version of the reaction, affording cyclic 1,2-diols [39]. Both arene chromium tricarbonyl (Eq. 29) and ferrocene complexes (Eq. 30) afford excellent yields of the desired products. 

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