Allyl carbonates radical cyclization

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.191 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.192 In these procedures the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 to 4 in Scheme 12.18 are examples of these procedures. Entries 5 and 6 show reactions carried out in the course of multistep syntheses. The reaction in Entry 5 followed a 5-exo radical cyclization and served to excise an extraneous carbon. The reaction in Entry 6 followed introduction of the allyl group by enolate alkylation. The aldehyde group in the product was used to introduce an amino group by reductive alkylation (see Section 5.3.1.2). 

A wide application of Newcomb s method provides a variety of N-heterocyc-lic systems, such as perhydroindoles, pyrrolizidines and aza-brigded bicycles [59, W, 146], The mild reaction conditions are compatible with several funtional groups of the substrate and several trapping agents to functionalize the cyclized product. 2-Substituted pyrrolizidines 132 are accessible by tandem cyclization of iV-allyl-substituted PTOC carbamate 131. In this case the allyl group on the nitrogen serves as an internal trap for the intermediate carbon radical. The Af-methylcyclohept-4-enaminium radical cation, produced from the corres-... 

Although radicals are not nearly so prone to rearrangement as are, for example, carbocations, there are a few such rearrangements which have become identified as characteristic of carbon radicals. These include radical cyclizations, particularly the 5-hexenyl radical cyclization, and radical C-C bond cleavages, particularly the cyclopropylcarbinyl to allyl carbinyl radical rearrangement. In hydrocarbon systems, as organic synthetic chemists have learned how to control rapid chain processes, such rearrangements have become important synthetic tools [176-179]. 

Srikrishna and co-workers have described cyclopentannulation of allyl alcohols by radical cyclizations as, protocols for the synthesis of sesquiterpenes. The total synthesis of 4-epibakkenolide-A 98 wherein two radical annulations were used for key carbon-carbon bond formations is illustrated [95CC469]. Radical cyclizations based on the 5-exo-dig pathway have been used as the key step in the total synthesis of sporothriolide and 4-epi-ethisolide [95TL2661] and in an approach to eriolanin skeleton [95TL2067],... 

More recently, van der Donk and coworkers reported radical cyclizations catalyzed by vitamin B12 using titanium(III) citrate as a stoichiometric reducing agent (Fig. 69, entry 17) [330]. Here /V-allylic 2-(isopropenyl) pyrroles 290 or allyl 2-phenylallyl ethers serve as the starting material in tandem hydrocobaltation/ radical 5-exo cyclization sequences giving dihydropyrrolizine derivatives 291 or 292. The mechanistic course is not completely clear. However, it is assumed that the reactions start with an initial hydrocobaltation of the isopropenyl unit in the presence of the allylic alkene (see Sect. 5.7). The benzylic cobalt intermediate is subject to homolysis of the very weak cobalt-carbon bond and initiates the radical 5-exo cyclization. Interestingly, the fate of the cyclized radical is dependent on the... 

The reactivity of allyl radicals does, however, appear to be sufficient for intramolecular radical reactions. In a systematic study. Stork and Reynolds investigated the feasibility of allyl radical 5-exo cyclizations. It was found that cyclization proceeds readily for a variety of systems, especially for those with geminal 3,3-diester substitution. Mixtures of c/s/frtms-cyclopentanes are formed as the major products, while 6-endo cyclization is hardly observed. Allyl radicals behave in this respect much like alkyl radicals. Cyclization is not even hindered by the presence of substituents at the attacked carbon... 

Sugars have also been used as chiral auxiliaries in acetal formation for diaste-reoselective radical cyclizations [52]. In Eq. (13.40) a chiral acetal is utilized to control the stereochemistry of a 5-exo-dig cyclization resulting in the formation of quaternary carbon-based stereocenters. Product 129 is formed as a single diaste-reomer in 35% yield. An allylic strain model is proposed to account for the stereochemical outcome of this reaction. 

The a-siloxyalkyl radical intermediate can be used for carbon-carbon bond formation by intra- and intermolecular trapping (Scheme 10.233). In the BUjSriH-mediated system, a bromoalkenoylsilane is efficiently converted into a bicyclic compound by tandem radical cyclization [601]. When allyltributylstannane is used instead of BuaSnH, the a-siloxyalkyl radical generated from a 5-bromoalkanoylsi-lane undergoes homolytic allylation to provide a homoallyl silyl ether [602]. 

To investigate whether the radical cations of the diazadithiafulvalenes would undergo eoupling with carbon radicals at a different rate than TTF+, eomparative experiments were performed with the allyl sulfide 99. This led to the products 100 and 101 as for TTF (Scheme 16). However the yield of the bicyclic produet was higher for the diaza compounds, indicating a slow-down in the kinetics of the recombination reaction. Although this is likely to be a fairly small change, it is clear that the modulation of kinetics in this way may be useful with radical-polar crossover reaetions to permit slower cyclizations to occur before recombination. 

Although the (bromomethyl)silyl ether connection has been more extensively utilized in radical cyclizations, Stork also introduced, at a similar time, the use of a mixed acetal function [51a, 73b, 80], This tether differs in that a two-carbon unit is introduced on the proximal carbon atom of the olefin, whereas the silyl tether allows the incorporation of only one carbon atom. The chemistry of this tether is dominated by 5-exo-trig cyclizations onto allylic double bonds which proceed with the usual degree of high stereoselectivity. 

Enholm EJ, Kinter KS. Eree-radical cyclization promoted by allylic 0-stannyl ketyls the intramolecular coupling of the P-carbons of activated alkenes. J. Am. Chem. Soc. 1991 113 (20) 7784-7785. 

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