Acylsilane, radical cyclization

Acylsilanes of type 152 with radicalphiles attached to the silicon atom underwent tandem radical cyclization to give 7,7,10-trimethyl-6-oxa-7-silaspiro[4.6]undecane (153 n = 1) and 8,8,ll-trimethyl-7-oxo-8-sila-spiro[5.6]dodecane (153 n = 2) (Equation 29) <2005T2037>. 

Radical cyclization using acylsilanes is apphcable to the synthesis of cychc silyl enolates by yS-elimination of the a-siloxyalkyl radical intermediate (Scheme 10.234) [603]. 5-Bromo-5-stannyl- and 5-bromo-2-sulfonyl-alkanoylsilanes are cychzed to cyclopentanone silyl enolates with ehmination of the stannyl and sulfonyl groups. 

Radical cyclization reactions have proven to be a very efficient approach for polycyclic natural product synthesis. In many cases, the last step involves a reduction of a cyclic radical with formation of a new stereogenic center. Very good stereochemical control has been achieved with such polycyclic radicals. For example, Beckwith has reported a highly stereoselective formation of a quinolizidine ring (Scheme 19, Eq. 19.1) [41b]. This process is the key reaction in a four-step synthesis of epilupinine and the stereochemical outcome results from a stereoselective axial reduction by tin hydride of a bicyclic radical. In a related process, Tsai has prepared silylated hydroxyquinolizidine by radical cyclization to an acylsilane followed by a radical-Brook rearrangement (Scheme 19, Eq. 19.2) [42]. 

Intramolecular radical cyclizations of acylsilanes containing the methyldiphenylsilyl moiety were investigated by the Tsai group (eq 29). As indicated in eq 29 products of radical addition to the carbonyl group involve silyl migration, whereas attack at the alkene center gives simple adducts. 

Radical cyclization of an acylsilane was the featured reaction in a formal synthesis of (—)-epiquinamide (e <-2104) by Chen and Tsai (Scheme 278). Acylation of the same dithiane-protected amine 647 that they used in their synthesis of (+)-swainsonine (cf Scheme 87 Section... 

Intramolecular competition experiments using a radical clock have revealed that the 5- and 6-exo cyclizations of primary alkyl radicals bearing an acylsilane moiety are slightly faster than those of the 5- and 6-alkenyl radicals [600]. The rate of cyclization depends on the substituents on silicon - the presence of a phenyl group on silicon increases the rate, probably because of its electron-withdrawing nature. 

Two alternative routes to (+)-swainsonine (ent-37S) developed by Chen and Tsai, Hke that used in their synthesis of lentiginosine (c Scheme 47 Section 3.3.2), created the bond to C-8a by means of free radical cycUzations onto an acylsilane. The first approach entailed the creation of the C-l/C-8a bond (Scheme 86). Amide formation between the amine 638 and the acid chloride prepared in situ from the chiral lactone-acid 639 yielded (—)-640, which was cyclized with base to the imide (—)-641 in 91% yield. Chemoselective reduction of the C-2 carbonyl group, acid-catalyzed reaction with thiophenol, and protection of the hydroxyl substituent as the benzoate gave 642 as a mixture of isomers. After hydrolysis of the dithiane to the acylsilane 643 with iodobenzene bis(trifluoroacetate), treatment with tri-butyltin hydride and l,lCazobis(cyclohexane-l-carbonitrile) (ACCN) as radical initiator produced the indohzidin-5-one 644 in 86% yield as a... 

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