Vinyl radical cyclizations

Scheme 3. Selected vinyl radical cyclizations developed by Stork and coworkers.

Vinyl radicals can also participate in 6-exo cyclizations. In pioneering work, Stork and his group at Columbia University showed that stereoisomeric vinyl bromides 20 and 21 (see Scheme 3) can be converted to cyclohexene 22.7 The significance of this finding is twofold first, the stereochemistry of the vinyl bromide is inconsequential since both stereoisomers converge upon the same product and second, the radical cyclization process tolerates electrophilic methoxycarbonyl groups. The observation that the stereochemistry of the vinyl bromide is inconsequential is not surprising because the barrier for inversion of most vinyl radicals is very low.8 This important feature of vinyl radical cyclization chemistry is also exemplified in the conversion of vinyl bromide 23 to tricycle 24, the key step in Stork s synthesis of norseychellanone (25) (see Scheme 4).9 As in... 

Scheme 4. Stork s vinyl radical cyclization strategy for the synthesis of norseychellanone (25)...

Curran2 has reviewed recent applications of the tin hydride method for initiation of radical chain reactions in organic synthesis (191 references). The review covers intermolecular additions of radicals to alkenes (Giese reaction) as well as intramolecular radical cyclizations, including use of vinyl radical cyclization. 

VINYL RADICAL CYCLIZATION VIA ADDITION OF TIN RADICALS TO TRIPLE BONDS... 

Free radical reactions are proving to be synthetically useful altern-atives for producing carbon-carbon bonds. Recently, Stork has shown that vinyl radicals are valuable in ring forming reactions since they place a double bond in a predictable position. Their compatibility with many unprotected functional groups and their ability to form quaternary centers are additional features which make vinyl radical cyclization an attractive synthetic method. 

Many examples of radicals kinetically favoring addition to double bonds over triple bonds are known.11 Yet, vinyl radical cyclization in the present procedure is initiated by the addition of a tin radical to a triple bond.12 The apparent selectivity of the tin radical for the triple bond in the presence of a double bond is, at least in some cases, a result of reversible addition to both followed by selective cyclization of the vinyl radical. ... 

Vinyl acetate- Acetic acid vinyl ester Acetic acid ethenyl ester, (108-05-4), 65, 135 VINYL CATION EQUIVALENT, 66, 95 Vinyl cation synthons, 66, 102 Vinyl radical cyclization, 66, 81, 82 VINYLAT10N OF EN0LATES. 66, 95, 104 Vinyl lithium, 66, 53, 55... 

Tri- and tetrasubstituted oxepanes 47 can be obtained in 50-60% overall yield (Scheme 15) using vinyl radical cyclization of homopropargyl and arylhomopropargyl derivatives 48 of Baylis-Hillman adducts 49, followed by methylidene group deprotection using pyridinium/>-toluenesulfonate (PPTS) <2005TL3369>. 

In the case of vinyl radical cyclizations of 49E , the intermediate silacycle could be oxidized under Tamao conditions to afford ketone 51 (2) [124], The consequence is an umpolung installation of an acetyl group, with the vinyl radical serving as an acyl anion equivalent, further expanding the synthetic potential of the Si-tethered radical additions. 

The alkyl radical cyclization onto an N-C double bond proceeds in both nitrogen-philic and carbon-philic modes (Scheme 4-50) [86]. On the other hand, vinyl radical cyclizations favor the carbon atom of the N-C double bond (Scheme 4-50) [87]. An important issue, in this regard, is the preference for acyl radical cyclization. 

Many other photochemically induced decompositions arise by carbon-halogen bond cleavage. The majority of these reactions are radical processes with little photochemical significance and are therefore not reviewed in detail in this Report. Interest is evident in photochemically generated vinyl radical cyclization. Irradiation in benzene of the vinyl azetidinone (140), for example, gave the 1a-methylcarbapenam (141) together with the reduction product (142). Products derived by both radical... 

Hart and Ghosh [43] have explored the 7-exo aryl and vinyl radical cyclizations for the construction of polycyclic systems as part of their tandem cycloaddition-radical cyclization strategies for polycycles. Treatment of the bromides 177-179 with BujSnH and AIBN furnished the tetra- and pentacyclic compounds 180-182 via stereoselective 7-exo trig cyclizations. 

During the last decade, the usefulness of the hydrostannation of acetylenes as the first step in the synthesis of cyclic compounds has been demonstrated vinyl radical cyclization by this route is a well-established synthetic strategy and this topic will be discussed in some detail in the next section. However, a mild procedure has recently been described, making use of triethylborane as initiator the EtsB-induced reaction shows two main features ... 

Throughout the course of their investigation of vinyl radical cyclization using A -alkenyl-7-bromo-substituted hexahydroindolinones, Padwa synthesized a pyrido [3,2,l-/ ]carbazolonone (53) in 81% yield as a result of cyclization of the radical onto the benzene ring [44]. 

Ryu I, Oguta S, Minakata S, Komatsu M (1999) Vinyl radical cyclization onto imino group. Selective 6-endo cyclizatimr onto aldimines leading to 3-methylenepiperidines. Tetrahedrmi... 

Padwa A, Rashatasakhon P, Ozdemir AD, Willis J (2004) A study of vinyl radical cyclization using N-aUceny 1-7-bromo-substituted hexahydroindolinones. J Org Chem 70 519-528... 

A section on cardenolides would not be complete without mentioning the total synthesis of (+)-digitoxinin by Stork and his co-workers. Protected Wieland-Miescher ketone 66 was converted into compound 67 via formation of the trimethylsilyl enol ether ozonolysis of the enol ether gave a mixture of hydroxyketones, which was reduced to the corresponding diol and then cleaved with sodium periodate to yield dialdehyde intermediate 67. Compound 67 was then elaborated into Diels-Alder precursor 68 in two steps. After completion of the Diels-Alder reaction, four additional steps led to the preparation of intermediate 69, which was ideally set up for a vinyl radical cyclization. Key intermediate 70 was then elegantly converted into (+)-digitoxinin (71). 

Another example of vinyl radical cyclization involving a methylene installation is found in Danishefsky s synthesis... 

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