Cyclization reactions 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)). ... 

Since the introduction of the titanocene chloride dimer 67a to radical chemistry, much attention has been paid to render these reactions catalytic. This field was reviewed especially thoroughly for epoxides as substrates [123, 124, 142-145] so only catalyzed reactions using non-epoxide precursors and a few very recent examples of titanium-catalyzed epoxide-based cyclization reactions, which illustrate the principle, will be discussed here. A very useful feature of these reactions is that their rate constants were determined very recently [146], The reductive catalytic radical generation using 67a is not limited to epoxides. Oxetanes can also act as suitable precursors as demonstrated by pinacol couplings and reductive dimerizations [147]. Moreover, 5 mol% of 67a can serve as a catalyst for the 1,4-reduction of a, p-un saturated carbonyl compounds to ketones using zinc in the presence of triethylamine hydrochloride to regenerate the catalyst [148]. 

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. ... 

In most cases, carbon-carbon bond formation occurs at the least substituted terminus of the allylic unit. A wide range of aldehydes and ketones can be utilized in the reaction, and one cyclization process has been reported (equation 16). Aromatic and a,3-unsaturated substrates cannot be used owing to cran-petitive pinacolic coupling reactions promoted by Sml2. 

Pinacol formation from carbonyl compounds promoted by Smij continues to interest chemists. In the presence of methyl chloroformate the products are cyclic carbonates. In a cyclitol synthesis the diastereoselectivity for cyclization is found to be dependent on the a-substituents of the aldehyde groups. Lithium halides (chloride, bromide) have a profound effect on the reactivity of Sml2 and the pinacol coupling is favored. The reduction and pinacol coupling of ketones in THF is accelerated by MejSiCl (reaction time from hours reduced to a few minutes)." ... 

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. 

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). 

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]. 

Olefin migration Oxidation of alcohols Passerini reaction Pauson-Khand reaction Pinacol cross-coupling Pinner reaction Polymerization of olefins Prins reaction Propargylation Radical addition Radical cyclization Radical substitution Reduction... 

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