Pinacols, cyclization

In summary, chiral solvents have only induced limited enantioselectivity into different types of photochemical reactions as pinacolization, cyclization, and isomerization reactions. These studies are nevertheless very important, because they are among the early examples of chiral induction by an asymmetric environ ment. Based on our classification of chiral solvents as chiral inductors that only act as passive reaction matrices, effective asymmetric induction by this means seems to be intrinsically difficult. From the observed enantioselectivities it can be postulated that defined interactions with the prochiral substrate during the conversion to the product are a prerequisite for effective template induced enantioselectivity. 

CpTiCl3/LiAlH4. Titanium-based reagents have also been employed in a new approach to propellane systems, including the quadrone ring skeleton (equation 35). More recently Takeshita et al. demonstrated the chemoselectivity of such reagents in a formal synthesis of cuparene (18 equation 36). Similar chemoselectivity is observed in pinacolic cyclizations promoted by TMSCl/Zn (equation... 

Trehazolamine. Chiara has described a synthesis of trehazolamine, the aglycon of trehazolin, a powerful inhibitor of trehalase, wherein a pinacol cyclization provided the necessary cyclopentane framework (Eq. 3.2) [17]. Thus, treatment of the tetrabenzyl-protected keto aldehyde, derived from D-glucose, with Sml2 furnished the two cis diols exclusively as a 1 1 mixture of isomers in excellent yield (>90%) [18]. Previous studies of five-membered ring formation mediated by SmE have also reported good cis/trans selectivity, presumably due to the intervention of a samarium chelate. 

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. 

Sarcophytol B. McMurry has utilized a diastereoselective pinacol cyclization of a 1,14-dialdehyde in the final step of a five-step synthesis of sarcophytol B, a cem-brane sesquiterpene (Eq. 3.8) [25]. This work established the relative stereochemistry of the natural product [26]. 

Isolobophytolide. McMurry has described a synthesis of isolobophytolide, a terpenoid component from a Pacific soft coral (Eq. 3.9) [27], A key step in the synthesis was a pinacol cyclization of a 1,14-ketoaldehyde with TiCl3(DME)i 5/Zn-Cu. Unfortunately, all four possible stereoisomeric diol products were generated, with the desired isomer being fonned in slight excess over the other three (21% 19% 11% 7%). 

Taxol. Nicolaou has reported the use of a pinacol cyclization to close the B ring of taxol, a diterpene of great interest due to its anticancer activity (Eq. 3.12) [30], The reaction proceeded in modest yield (23%), with two of the major side products being a lactol and an olefin. 

Mukaiyama has described a total synthesis of taxol wherein pinacol cyclization of a diketone was employed to construct the A ring in good yield (Eq. 3.13) [31J. In this work, partially reduced alcohols and rearranged compounds were the major side products of the titanium-mediated coupling process. 

For a stereoselective synthesis of myo-inositol using a Sml2 inediated pinacol cyclization, see Chiara, J. L. Martin-Lomas, M. Tetrahedron Lett. 1994, 35, 2969-2972. 

Pinacol cyclizationA key step in a new method for carbocyclic synthesis applicable to gibberellic acids involves the pinacol cyclization of (1) to (2). This was accomplished, in 75 % yield, by addition of (1) to a mixture of magnesium amalgam (7.5 eq.) and dimethyldichlorosilane (2 eq.) in dry THF at 25° followed by subsequent alkaline... 

The observed stereochemical induction and the retention of olefin configuration during the rearrangement are consistent with a mechanistic scheme in which pinacol cyclization of the ( )-oxonium intermediate 32 (X = O) occurs through a chairlike conformation in which the homoallylic substituent R2 adopts an equatorial orientation subsequent [1,2] migration via the chairlike conformation 33 results in the formation of stereochemically defined heterocyclic products. 

Oxidation of 12 with excess Collins Reagent in methylene chloride yields the sensitive keto aldehyde 13. A pinacol cyclization of the keto aldehyde 13. to the tricyclic intermediate 14 is accomplisehd by reaction with finely powdered metallic Titanium inTHF. 2, 13 Oxidation to the ketol without appreciable glycol cleavage can be readily accomplished via an oxysulfonium intermediate. 14, 15 "phe ketol can then be converted to the MEM ether derivative by treatment with MEM chloride and diisopropylethylamine in methylene chloride at reflux to give the MEM ether derivative 15. ... 

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... 

Pinacol Reaction. Dichlorodimethylsilane (1) allows clean pinacol cyclization of a keto aldehyde to occur without competition from an aldol reaction (eq 1). ... 

Protection. The success of the pinacol cyclization is due to the formation of a siliconide , the silicon equivalent of an ace-tonide. Reaction of a diol with (1) in the presence of base also provides these cyclic silicon compounds (eq 2). However, the labile dimethylsiliconide does not afford a widely applicable form of protection for this functional group, although it has found some use with pericyclic reactions. ... 

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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