Stannyl radical addition-cyclization

Stannyl radical addition-cyclization of oxime ether 183 [31] was also examined (Scheme 44). In this case vinyl stannane 185 was obtained in 77% yield. 

Reactions of oxime 186, containing an electron-deficient carbon-carbon double bond, were also investigated (Scheme 45) [31]. In the case of stannyl radical addition-cyclization using triethylborane as the radical initiator, the reaction proceeded as efficiently as in previous cases giving the cyclized product 188 in 64% yield, after base-induced cleavage from the resin and hnker. 

Scheme 43 Stannyl radical addition-cyclization by Naito [31]...

Each of the syntheses of seychellene summarized in Scheme 20 illustrates one of the two important methods for generating vinyl radicals. In the more common method, the cyclization of vinyl bromide (34) provides tricycle (35).93 Because of the strength of sjp- bonds to carbon, the only generally useful precursors of vinyl radicals in this standard tin hydride approach are bromides and iodides. Most vinyl radicals invert rapidly, and therefore the stereochemistry of the radical precursor is not important. The second method, illustrated by the conversion of (36) to (37),94 generates vinyl radicals by the addition of the tin radical to an alkyne.95-98 The overall transformation is a hydrostannylation, but a radical cyclization occurs between the addition of the stannyl radical and the hydrogen transfer. Concentration may be important in these reactions because direct hydrostannylation of die alkyne can compete with cyclization. Stork has demonstrated that the reversibility of the stannyl radical addition step confers great power on this method.93 For example, in the conversion of (38) to (39), the stannyl radical probably adds reversibly to all of the multiple bond sites. However, the radicals that are produced by additions to the alkene, or to the internal carbon of the alkyne, have no favorable cyclization pathways. Thus, all the product (39) derives from addition to the terminal alkyne carbon. Even when cyclic products might be derived from addition to the alkene, followed by cyclization to the alkyne, they often are not found because 0-stannyl alkyl radicals revert to alkenes so rapidly that they do not close. 

When oxime benzoates, prepared by benzoylation of dialkyl 1-hydroxyiminophosphonates in the presence of Py, are submitted to the action of tin hydrides under radical conditions, the weakness of the N-0 bond is responsible for the fast formation of the reactive iminyl radical. In the example displayed in Scheme 7.71, the intermediate iminyl radical undergoes cyclization faster than the P-scission to nitrile to give a cyclic aminophosphonale. "- The reaction has also been explored with dialkyl l-benzoyloxyimino-2,2-dimethyl-3,4-pentadienylphosphonate and BujSnH/AIBN in refluxing cyclohexane. In this case, the iminyl radical generated by stannyl radical addition on the benzoyl moiety leads to the sole formation of phosphonylated dihydropyridine in quantitative yield. ... 

If selenide additions are carried out in the presence of tri- -butylstannane, the radical generated by addition can be reduced by hydrogen abstraction. The chain is then continued by selenide abstraction by the stannyl radical. This leads to nonselenated addition and cyclization products. 

A radical cyclization of this type was used to synthesize the 4-amino-5-hydroxyhexahydroazepine group found in the PKC inhibitor balanol. The cyclization involves an a-stannyloxy radical formed by addition of the stannyl radical to the aldehyde oxygen. 

Entry 21 involves addition to a glyoxylic hydrazone and the cis ring junction is dictated by strain effects. The primary phenylselenyl group is reductively removed under the reaction conditions. Entry 22 involves generation of a stannyloxy radical by addition of the stannyl radical at the carbonyl oxygen. Cyclization then ensues, with the cis-trans ratio being determined by the conformation of the cyclization TS. 

It is presumed that the stannyl radical, by addition to the terminal position of the triple bond in allenynes 132, or through bromine abstraction in bromovinyl and haloaryl allenes 134 and 136 gives the vinylic radical intermediates 138 and 142 in the propagation step, followed by cyclization toward the central carbon bond of the... 

Michael addition of pentM-yn-1-thiol to an activated alkyne produces co-yne vinylsulfides 424 as a separable mixture of the E and Z isomers. On treatment with -Uu (SnI I and a radical initiator, these substrates undergo a double radical cyclization accompanied by [(-fragmentation of the stannyl radical. The process is regio-, chemo-, and stereo-selective and produces the -isomer of the 5-substituted 3,4-dihydm-2//-thiopyran (Scheme 134) <1997JOC8630>. 

The polymer-supported distannane 90 was used as a source of stannyl radicals in several radical cyclization reactions, such as the photochemical radical chain addition of f-butyl iodide to acetylenes yielding the Z/E mixture of alkenes or the photochemical cyclization of citronellyl bromide to give menthane in high yields164 (Scheme 44). 

The live-ring closure of prostereogenic radicals constructs two new stereogenic centers with good diastereoselectivity, as demonstrated by the trimethyltin hydride mediated cyclization of an ester-substituted diene4. The reaction proceeds via regioselective addition of the stannyl radical to the terminal end of the less substituted alkene and subsequent cyclization. 

The free-radical cyclization of enynes as a synthetic strategy was introduced by Stork and coworkers using BusSnH/AIBN-mediated ethynyl cyclization (equation 34) ". From a mechanistic point of view, the first step is the selective addition of the stannyl radical to the triple bond of the enyne generating a vinyl radical, which can cyclize onto the double bond. In the absence of the methyl substituents on the olefinic moiety, the groups of Beckwith and Stork have both postulated, and demonstrated with the aid of kinetic studies, that the 6-endo radical 30 arises from a ring expansion of the kinetically favored... 

Opening of the (Cy ) radical, formed by abstraction of hydrogen from a fi-methylene group, to A, which can be trapped by EtBr to give 145 (Scheme 66). From this result, cyclization of unsaturated stannyl radicals does not appear to be a likely process, in agreement with the well-known reversible addition of stannyl radicals to double bonds. ... 

Kim reported efficient radical cyclizations involving azides as radical traps (Scheme 8.33)7 This intramolecular amination process is efficient and proceeds via a 3,3-triazenyl radical that readily eliminates nitrogen to afford an aminyl radical. The use of (TMSlsSiH gives better results than BusSnH since azides are relatively inert toward tris(trimethylsilyl) silyl radicals. However, tin hydride can be used with alkyl iodides since the iodine atom abstraction by the stannyl radical is faster than its addition to the azide. 

More interesting reactions are possible when the carbonyl-alkene cyclizations are applied in a tandem reaction sequence [4b]. The three precursor motifs of spiro , separated , and fused ring systems 22, 24 and 26, respectively, were each constructed however, not all cyclized readily (Scheme 6). In each reaction the intermediate alkene bearing the EWG, which both receives the radical and transfers the radical in the last cyclization, was activated for addition from the <9-stannyl ketyl. With the appropriate placement of the alkene tether in the starting substrate, complex ring structures can be synthesized in a one-pot procedure. 

The -fragmentation can be used as one of the cascade steps in processes which do not start from the addition of a sulfur-centered radical. Rearrangements of sulfur compounds, catalyzed by tributylstannyl radical, which lead to 3-vinyldihydrothiophene or dihydrothiopyran derivatives, have been developed [70]. The mechanism is shown in Scheme 15 the cyclic y9-thioalkyl radical 9, produced in two steps, fragments, thus producing the thiyl radical 10, which cyclizes in a 5- or 6-endo fashion onto the stannylated double bond subsequent elimination leads to the final heterocyclic compound. 

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