Bu3SnH radical cyclization

The silicon containing (5 5 5) heterocycle 32 has been efficiently synthesized starting from. Y-prolinc 375 via silanes 376, 378, and 379. The final step has been achieved via radical cyclization. The amine 377 was treated with COCl2 and the resulting carbamoyl chloride 378 reacted with PhSeNa to give the radical precursor 379 (84% overall yield from 376). Compound 379 when refluxed with Ph3SnH or Bu3SnH in the presence of AIBN afforded the desired heterocycle 32 in 75% yield (Scheme 81). 

The construction of the central ring can also be accomplished by a radical cyclization of a non-fused heterobiaryl system composed of two six-membered heterocycles and linked by a two-atom bridge. An example is the synthesis of 106 from the bromo derivative 105 in the presence of AIBN and Bu3SnH (Equation 8) <1999TL4073>. 

The alkaloid whitasomnine 44 was prepared according two different routes. The first approach (route A) was based on the cyclization of the l-(3-chloropropyl)cyclopropanol 41 (Scheme 3). The final cyclization involved the reaction of 3-(3-chloropropyl)pyrazole 42 to form the final pyrazole 43 in 40% yield, which is then transformed to the natural product <1996TL1095>. The second approach (route B) is based on the radical cyclization of the substituted pyrazole 45 in the presence of Bu3SnH in acetonitrile under refluxing toluene. Whitasomnine 44 was isolated in 38% yield <2002TL4191>. 

Partially saturated derivatives can also be prepared through aryl radical cyclization of A-2-halobenzoyl cyclic ketene-iVA-acetals <2005TL3801>. In this event, treatment of ketene-acetal 418 with Bu3SnH afforded good yield of cyclized products 419 and 420, as a mixture of two diastereoisomers, but with a total regioselectivity (Scheme 108). 

Radical cyclization to macrolides.111 Cyclization of iodoalkyl acrylates (1) by reaction with Bu3SnH (1 equiv.) in the presence of AIBN is useful for formation of macrolides (2) containing 11 or more members. Similar cyclization of iodoalkyl fumarates (3) results in two macrolides with the endo-product predominating except when n is 16 or higher. Tertiary iodides undergo this free radical cyclization more... 

Rate constants for reactions of Bu3SnH with some a-substituted carbon-centered radicals have been determined. These values were obtained by initially calibrating a substituted radical clock on an absolute kinetic scale and then using the clock in competition kinetic studies with Bu3SnH. Radical clocks 24 and 25 were calibrated by kinetic ESR spectroscopy,88 whereas rate constants for clocks 26-31 were measured directly by LFP.19,89 90 For one case, reaction of Bu3SnH with radical 29, a rate constant was measured directly by LFP using the cyclization of 29 as the probe reaction.19... 

A free radical cyclization of oxime ethers tethered to an aldehyde has been used in the synthesis of azepine derivatives . For example, oxime ether 389 is cyclized to azepine 390 by reaction with Sml2 in HMPA and f-BuOH at —78°C (equation 170) . Similar free radical cyclization of oxime ethers can be carried out also in the presence of Bu3SnH/AIBN in benzene . Oxime 0-methyl ether 391 underwent thermal cyclization in refluxing o-dichlorobenzene (ODCB) leading to the mixture of two products 392 and 393 in ratio 69 31 in overall yield of 91% (equation 171) °. Rearrangement of oxime 0-tosylates in the presence of piperidine also leads to azepine ring formation . ... 

The use of Lewis acids in controlling the stereoselective outcome of radical cyclization reactions has been explored, in particular the effect of aluminium-based Lewis acids using low temperature Et3B/Bu3SnH-initiated procedures.171,172 For example, cyclization of propargyl ether (78) or allyl ether (79) in the presence of Lewis acid (80) can completely reverse the normal selectivity (Scheme 34).171 The effect of aluminium Lewis acids on the diastereoselectivity of 6-exo cyclization of unsaturated chiral menthol esters has been studied.172 Cyclization at low temperature in the presence of the Lewis acid MAD modified the de of the reaction from 31 to 98%. 

Scheme 34 Preparation of benzocarbapenem 106b using radical cyclization (i) Bu3SnH (1.2 equiv), AIBN (0.1 equiv), benzene, reflux, 1.5 h (ii) 10% aqueous KF, 30 min...

The formation of bicyclo compounds by the radical cyclization of alkenes with strategically placed phenylseleno groups, promoted by Bu3SnH, occurs in high yields and gives... 

The kinetics of 5-exo and 6-endo acyl radical cyclizations have been investigated under a variety of reaction conditions.28 The presence of the 6-endo product was found to arise either by a direct cyclization (2.0 x 104 s-1) or by a ring expansion (4.2 x 103 s 1) from the 5-exo radical product (1.6 x 105 s-1). Consequently, cyclization in the presence of high concentrations of fast H-donors (e.g. Bu3SnH) furnished 5-exo products whereas reactions under high dilution conditions or with poor H-donors gave rise to 6-endo products. 

A concise free radical cyclization process has been applied to the synthesis of new cyclopentanone-annulated azepines 204 from chiral vinylogous amides (Scheme 26). The free radical was generated from the phenylselenide group in 203 (made in turn by N-acylation of 202) using Bu3SnH and l,l -azobis(cyclohexanecarbonitrile) (ACN), as the initiator <2004SL1917>. 

Stereoselective radical cyclization (Equation 20) initiated by Bu3SnH/AIBN or Bu3SnH/Et3B is suggested as a method for the synthesis of O-linked oxepane ring systems (AIBN = 2,2 -azobisisobutyronitrile) <1998TL2783>. 

Diastereoselective 6-exo-trig radical cyclization of (—)-perhydro-l,3-benzoxazines 69, 71, 74 with Bu3SnH and AIBN gave a diastereomeric mixture of perhydropyrido[2,l-Z>][l,3]-benzoxazines 39, 70, and 72, 73, and 40, 75, respectively (00TA2809). 

Acyl radical cyclization to cyclohexanones.n Acyl radical cyclization to five-membered rings is well known, but this reaction is also useful for synthesis of substituted cyclohexanones as shown by a recent synthesis of the a-methylenecyclo-hexanone 3. Thus treatment of the selenol ester 1 with Bu3SnH and AIBN in C6H6 at 80° provides a 1 1 mixture of cyclohexanones 2 in 91 % yield. Oxidation of 2 with... 

Chmielewski and colleagues reported a Bu3SnH-mediated radical-induced isoxazoli-dine-isoxazolidin-5-one transformation (equation 99)778, while Sulsky and coworkers described conformational switching in the synthesis of a spiro[2H-indol]-3(lH)-ones (e.g. 122) by radical cyclization, an example of which is depicted in equation 100787. In this final example, Takekawa and Shishido described the selective cleavage of substituted cyclopropanes via stannane-induced radical fragmentation, an example of which is illustrated in equation 101791. 

Eq. 3.6 shows the direct preparation of furan derivative (19) by the successive treatment of vinyl ethers with propargyl alcohol/NBS, radical cyclization with Bu3SnH/AIBN, and lastly, aromatization with p-TsOH. 

Treatment of epoxide (34) with Bu3SnH/AIBN in the presence of Mgl2 first forms iodohydrin synthon, which rapidly reacts with Bu3Sn to form a cyclohexanol derivative (35) via 6-exo-trig ring closure of (3-hydroxyl radical as shown in eq. 3.12 [50-54]. Since the epoxides can be obtained from alkenes with peroxides, this is an indirect radical cyclization method of alkenes. 

Stereoselective synthesis of (+ )-botryodiplodin was carried out by a radical cyclization of dibromoacetal (203) containing an allene group, with Bu3SnH initiated by Et3B, through the 5-exo-trig cyclization, and the subsequent debromination with bulky... 

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