Pinacol coupling, Sml2-mediated

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)). ... 

Enantioselective synthesis of /3-amino alcohols by Sml2-mediated cross-pinacol coupling of the planar chiral iV-sulfonyl(ferrocenylidene)amine with ferrocene carboxaldehyde is achieved by facile reduction of the ferrocenyli-dene amine with Sml2, followed by enantioselective addition to the aldehyde (Equation (75)). ... 

Sml2, which can be prepared conveniently from samarium powder and 1,2-diiodoethane in THF, finds application as a versatile one-electron reducing agent in organic synthesis. Two typical synthetic procedures mediated by Sml2 are the pinacol coupling of aldehydes and the Barbier reaction, as shown in the following schemes ... 

Nickel catalysts display significant accelerating effects in reactions mediated by Sml2 [25], such as aza-pinacol coupling reactions of imines [26, 27]. 

The stereoselectivity of Sml2-mediated pinacol couplings depends highly on the substrates used. In contrast to the intermolecular cases, high levels of diastereoselectivity can be attained in the cyclisation of a variety of 1,5- and... 

The intramolecular Sml2-mediated pinacol coupling has been well exploited as a key step in many natural product syntheses for the construction of different ring sizes. For example, in 1997, Pancrazi reported a formal total synthesis of... 

Scheme 39 An example of a Sml2-mediated intramolecular pinacol coupling...

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

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... 

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. 

Another cyclization method towards synthesis of myo- inositols and chiro-inositols resulted from a Sml2-promoted intramolecular pinacol reaction. Treatment of dienes 34 and 35 with ozone produced a dialdehyde after reduction of the ozonide with dimethyl sulfide. Subsequent Sml2-mediated pinacol coupling gave the corresponding protected inositols as a mixture of diastereomers [89]. 

Reduction. Carboxylic acids, esters, amides, and nitriles are reduced very rapidly by Sm and hydrochloric acid. Ytterbium may be used instead of samarium. The reduction of a-halocarbonyl compounds and the pinacol coupling with Sm in an aprotic system (MejSiCl-Nai/MeCN) are as efficient as those mediated by Sml2. 

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