Pinacol coupling enantioselectivity

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

This method was later applied to samarium diiodide initiated reactions [26] and to tita-nocene-catalyzed pinacol couplings [27]. The first examples of enantioselective reactions using Me3SiCl as a mediator for catalysis have very recently been reported by Cozzi et al., as shown in Scheme 12.14 [28]. 

Asymmetric pinacol coupling reactions with a stoichiometric amount of titanium salts have been observed using a combination of TiGL and chiral amines such as A,A,A,A-tetramethyl-l,2-cyclohexanediamine and 2-methoxy-methylpyrrolidine. " " In these reports, the titanium salt is considered to be TiGl2- However, the titanium salt prepared by reduction of TiGU with McsSiSiMcs has proved to be TiGL. The enantioselectivities of the reactions using the chiral amines are modest (Table 2). 

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)). ... 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

Enantioselective Pinacol Coupling of Aldehydes A. Bensari, J. -L. Renaud, O. Riant, Organic Letters 2001, 3, 3863... 

A crossed-pinacol coupling was reported using Et2Zn and with a BINOL catalyst gave good enantioselectivity. A combination of Mg and MeaSiCl was also used to a crossed-pinacol. ... 

Chiral additives with pinacol couplings lead to formation of a diol with moderate to good enantioselectivity. Chiral metal complexes in conjunction with a metal leads to diol formation with good enantioselectivity. " ... 

Periplanone C. McMurry has reported an enantioselective synthesis of (-)-periplanone C, a sesquiteipene that serves as a sex pheromone for cockroaches, through a route involving a pinacol cyclization of a 1,10-keto aldehyde (Eq. 3.7) [24]. MM2 calculations based on a model for predicting the stereoselection of titanium-mediated pinacol coupling reactions were in qualitative, but not quantitative, agreement with the experimental results. 

Full details for the preparation of dichloro ansa-bis-Ind and /msv2-bis(tetrahydroindenyl) titanium derivatives with the 2,5-diisopropylcyclohexane bridging group (Scheme 662) have been reported along with their X-ray structures. The compounds were used to catalyze the enantioselective pinacol coupling of benzaldehyde.1682... 

Pinacol coupling reactions also involve radical-radical recombinations thus, enan-tiocontrol in these reactions remains a daunting problem. Initially it was found that addition of TMEDA as an additive increased the solubility of TiCl2, thus increasing the conversion of the aldehyde to diol product [19]. It was hypothesized that addition of an optically active amine would not only help to solubilize the Lewis acid, but also offer enantiocontrol in the coupling. When chiral diamines such as 41 were added, modest levels of enantioselectivity were achieved (Eq. 14). 

Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

Scheme 9.21 First catalytic and enantioselective pinacol coupling using a chiral vanadium complex, reported by Dai. ...

Four new asymmetric ansa-zirconocene dichlorides, rac-[l-(9-ri -fluorenyl)-2-(2-phenyl-l-ri -indenyl)ethane]zirconium dichloride, rac-[(9-ri -fluorenyl)(5,6-cyclopenta-2-methyl-l-ri -indenyl)dimethylsilane]zirconium dichloride, rac-[(9-ri -fluorenyl)(2-methyl-l-ri -indenyl)dimethylsilane]zirconium dichloride and rac-[(9-r -fluorenyl)(2-phenyl-l-ri -indenyl)dimethylsilane]zirconium dichloride, have been prepared and evaluated as propene polymerisation catalysts. The synthesis of the [2,5-diisopropylcyclohexane-l,4-bis(indenyl)]titanium dichloride and [2,5-diisopropylcyclohexane-l,4-bis(tetrahydroindenyl)]titanium dichloride complexes, shown as 20, and their use as catalysts for the enantioselective pinacol coupling of benzaldehyde have been described. ... 

Rono LJ, Yayla HG, Wang DY, Armstrong ME, Knowles RR (2013) Enantioselective photoredox catalysis enabled by proton-coupled electron transfer development of an asymmetric aza-pinacol cyclization. J Am Chem Soc 135 17735-17738... 

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

A highly enantioselective photoredox catalysis involving proton-coupled electron transfer has been developed to achieve the asymmetric aza-pinacol cyclization of (17), which leads to the corresponding 2-amino substituted cyclohexanols." Likewise, a photocatalyst/enzyme system has been applied to the asymmetric reduction of acetophenones with solar light, to afford the corresponding secondary alcohols with excellent enantioselectivity. ... 

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