Ester-Tethered Radical Cyclizations

The radical addition to 1-alkenyl or 1-alkynylboronic esters or amides took place extremely smoothly because the boron atom stabilizes the resulting ct-radical intermediates. Bu3SnH and PhSH predominated the trans-addition products 287 in the addition to 1-alkynylboronic amides at 90 °G, whereas Bu3SnH and Ph2Ph produced the m-addition products 288 at 0°C (>98% Equation (82)).455 Intramolecular addition to 1-alkenylboronic esters has been demonstrated in boron-tethered radical cyclization that provided 1,3- or 1,4-alkanediols 290 via oxidative workup (Equation (83)).456 Inter- and intramolecular additions of alkyl radical457 and sulfonyl radical458 have also been studied. 

Fraser-Reid s stereocontrolled synthesis of the Woodward reserpine precursor 195 relied upon a tandem 5-exol6-exo radical cyclization of pyranose-derived dienes [76-77]. As outlined in Scheme 36, a,P-unsaturated ester 188 was prepared by free radical coupling of iodide 187 with a tin acrylate. After hydrolysis of 188 (MeONa, MeOH, 100%) to give primary alcohol 189, the silicon tethered diene 190 was installed by silylation. Treatment of 190 with n-BujSnH led to the desired cage molecule 192 in high yield via a 5-exo-trig cyclization to intermediate 191 followed by a 6-exo cyclization. Tamao oxidation of tricycle 192 led to diol... 

Scheme 51), Weavers utilized direct formation of the a-iodomethylene-y-butyrolactone 148 from the propiolate 147 via atom transfer cyclization. Alke-noyloxymethyl iodides and selenides were converted into lactones upon treatment with tributylstannane or tributylgermane [101], In the (—)-zearalenone (152) synthesis reported by Pattenden [102] (Scheme 52), the ester tether is a bystander in the radical macrocyclization. 

Scheme 10-62 Tethering the radical acceptor and precursor through an ester linkage allows stereoselective radical cyclization of 3 -phenylseIeno thymidine nucleosides.

Annulation reactions are possible when a precursor monocyclic substrate contains an activated alkene in a tether [4a]. As demonstrated in Scheme 5, an ester was employed to activate the olefin appended to cycloalkanone 17. Upon generation of the 0-stannyl ketyl with tributyltin hydride, the carbon-centered radical attacks the electron-poor /(-position on the activated alkene. The corresponding cyclized adduct 18 is a bicyclic skeleton with a bridgehead hydroxyl group. An example of this reaction shows cyclopentanone 19 undergoing cyclization to diquinane 20 and tricycle 21 (76 24) in 69% yield. The presence of reasonable amounts of the minor, yet readily isolable, jn-diastereomers in the reaction indicated that the reaction may not be reversible. 

Bennasar also recently extended their interest in the cyclization of A -alkenyl substituted 2-indolylacyl radicals towards the annulation of larger rings [126]. A 7-endo-mg closure was observed when brotnovinyl substituted seleno ester 237 was treated with excess tin hydride in EtaB. In addition to the desired azepino[3,2-I>] indole 238, the 6-exo cyclization product 239 was observed as the minor product, with both products showing no evidence of the bromine atom in their strucmres. Previous attempts at this cyclization using a tethered allyl moiety, rather than the 2-bromo-2-propenyl tether, also gave the azepinoindole but only as the minor product. 

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