Radical homoallyl

The regiochemical control of Pd-catalyzed hydnde transfer reacdon is much more effeedve than that of the radical denitradon, as Shown in Eq 7 98 The base-catalyzed reacdon of nitroolefins with aldehydes followed by denitradon provides a new syntbedc method of homoallyl aicohols fEq 7 99 Exomethylene compounds are obtined by denitradon of cyclic allylic nino compounds with PdfO, HGO-,H and Et- N fEq 7 100 ... 

As the final example in this section, a Li-mediated carboaddition/carbocycliza-tion process will be described. Thus, Cohen and coworkers observed a 5-e%o-trig-cy-clization by reaction of the lithium compound 2-349 and a-methyl styrene 2-350 to give 2-352 via 2-351 (Scheme 2.82). Quenching of 2-352 with methanol then led to the final product 2-353 [189]. In this process, 2-349 is obtained by a reductive lithia-tion of the corresponding phenyl thioether 2-348 with the radical anion lithium 1-(dimethylamino)naphthalenide (LDMAN) (2-354). Instead of the homoallylic substance 2-348, bishomoallylthioesters can also be used to provide substituted six-membered ring compounds. 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

In support of a radical pathway for such reactions, both cyclopropylcarbinyl bromide and iodide gave rise to appreciable homoallylic substitution product with the foregoing metallostannanes. In contrast, the corresponding chloride and tosylate gave only the unrearranged product. 

An unexpected C-arylation was observed by Sherburn et al. in an attempted radical deoxygenation of a homoallylic secondary alcohol 83 via its thiocarbonyl-derivative 84 (scheme 17).1511 Thus, reaction of 84, obtained from 83 with ArOC(=S)Cl, with nBu3SnH yielded the 10-aiyl compound 87 As inter-... 

J(P1)427>. The regioselectivity of the second radical cyclization depends on the electronic nature of the homoallylic double bond pyrrolizinones 240 which result from a final 5-o -cyclization mode are preferred in the case of electron-poor carbon-carbon double bonds, such as enones or enoates electron-rich double bonds lead to indolizinones via a final 6-f db-cyclization. The best yields of pyrrolizinones were observed with iodide precursors. The cir-isomers of 240 predominate in this 5-f rf6i-5-f3co-cyclization. 

A recent study has indicated that the skeletal rearrangement step in the B12-catalysed isomerization of methylmalonyl-CoA to succinyl-CoA occurs not by a radical pathway but by an anionic or organocobalt pathway. A computational study of the isomerization of allyl alcohol into homoallyl alcohol by lithium amide has pointed to a process proceeding via a transition state in which the proton is half transferred between carbon and nitrogen in a hetero-dimer. l,l-Dilithio-2,2-diphenylethene... 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

The addition of substituted allylic zinc reagents to aldehydes is usually unselective" . Furthermore, the direct zinc insertion to substituted allylic halides is complicated by radical homocoupling reactions. Both of these problems are solved by the fragmentation of homoallylic alcohols. Thus, the ketone 166 reacts with BuLi providing a lithium alcoholate which, after the addition of ZnCl2 and an aldehyde, provides the expected addition product... 

Another important rearrangement is that of cyclopropylmethyl radicals to the corresponding homoallyl radicals. This is an exceptionally fast reaction (t1/2 10 8) and has been used as a radical clock to determine the rates of other free-radical reactions.95 Cyclopropylcarbene also undergoes rearrangement, leading to cyclobutene.96... 

The equilibrium between homoallyl and cyclopropylmethyl radicals favors the former (i.e. kf kQ) in the parent as well as in simple, alkylated systems (equation 38). Hence, to... 

The selective or partial reduction of dihalocyclopropanes to monohalocyclopropanes107 can be achieved with LAH108 or Bu3SnH (equations 32 to 34).109,11° A number of other reducing agents also lead to partial reduction. Reduction of dihalocyclopropanes proceeds via radical intermediates and the cyclopropyl radical thus generated can be trapped by an adjacent homoallylic double bond leading to a bicyclo[3.1.0]hexane system (equation 35).111,112... 

The asymmetric rearrangement of peroxy radical (5) has recently been used as the key step in the asymmetric synthesis of Plakorin (Scheme l).17 The thermal isomerization of buta-1,2- to buta-1,3-diene has been studied using ab initio calculations and the mechanism concluded to proceed stepwise via radical intermediates.18 The competition between cyclopropyl formation and the homoallyl-homoallyl radical rearrangement has been studied in the radical (6) and found to give the 3-exo cyclization product (7) and the rearranged product (8) in a 1 5 ratio, respectively, under the conditions shown (Scheme 2).19... 

Formation of trapping product 140 in over 54% yield provides strong support for preferential formation of the first bond at the w-carbon, as could be predicted by the rule of five . Higher trapping yield (65%) was obtained in the irradiation of 137 (R = t-Bu) at 50 °C. Formation of the Z-trapped product 141 and the /Z ratio of the trapped products 140/141 (52 13 respectively) could be attributed to an equilibrium between the cyclopropylcarbinyl radical 138 and its corresponding homoallyl radical. However, further studies are required to verify this assumption (Scheme 30). 

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