Cyclization, radicals with allenes

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

Most of the recent synthetic developments in the field of radical cyclization have involved the reactions of carbon-centered radicals with alkenes and alkynes. Other useful acceptors include allenes,31 dienes30 and vinyl epoxides.32 The same methods are used for cyclizations to these acceptors as for radical additions, and the preceding chapter should be consulted for specific details on an individual method (the organization of this section parallels that of Section 4.1.6). Selection of a particular method to conduct a proposed cyclization is based on a variety of criteria, including the availability of the requisite pre-... 

The allene functionality is also useful in radical cyclizations. Radical precursor 867 (R=OH OAc SePh) is readily cyclized to a 5 1 mixture of 868 and 862 together with two other cyclic compounds. After separation of the desired product 868, the methyl group is oxidized to an alcohol and then acetylated. Finally, the carbonyl groups are reduced to give ( + )-heliotridine (850) [191]. 

Radical reactions ofallenes are largely unknown [57]. Recently, Ma and coworkers [58] developed the first example of a radical addition/cyclization reaction of allene-enes in an alkene-to-allene manner (Scheme 5.32). The reaction of the allene 146 and polyfluoro alkyl iodide 147 with zinc powder as a cheap, readily available, efficient, and mild initiator led to 148 in moderate to good yields (53-86%), which on treatment with TBAF (tetra-n-butylammonium fluoride) gave the allene 149. 

The investigation of various parameters of the cyclization of enyne-allene 12, using the density frinctional theory (DFT), has been undertaken.This includes the thermodynamics for both C2-C7 (leading to 13) and C2-C6 (leading to 14 and called Schmittel reaction) reaction pathways. Theoretical calculations address the regioselectivity of diradical cyclization in enyne-allene with a different substitution. This study rationalizes the switch between the two radical cyclizations (C2-C7 vs. C2-C6) on the basis of mainly steric (12, = t-Bu) or electronic effects (R =... 

Reactions with other radical initiators, such as AIBN, were reported as well the desired dihydrobenzofurans could be produced selectively. Besides the cyclization of alkenes mentioned previously, intramolecular cyclization of allenes and allq nes was reported as well. In 1995, Grigg and coworkers developed a palladium-catalyzed cyclization-amination of allenes. They demonstrated that the effect of the base was obvious—different regioselectivities were observed by using K2CO3 and Ag2C03 as bases. The corresponding heterocyclic compounds were isolated in good yields (Scheme 2.42). 

The kinetic competition between C -C and C -C cyclization of enyne-allene 3.535 is determined by the nature of substituents in the acetylene branch. Hydrogen or n-alkyl substituents lead to the domination of the C -C reaction to form naphthalene derivative 3.538, while substituents stabilizing the radical and bulky substituents at QJ favor the C -C process and the formation of cyclised compounds 3.539 and 3.540 (the formal product of the Diels-Alder reaction with = Ph) (Scheme 3.35) [269aj. 

Radical C -C Myers-Saito cyclization of enyne-allene, as well as the reaction of C -C cyclization do not depend on the donor properties of the solvent [427]. For enyne carbodiimides the situation is different, because the nitrogen atom is a potential donor center and is well known for the high electrophilicity of the central carbon atom of the car-bodiimide group. Indeed, the study of the thermolysis of carbodiimide 3.971a showed a strong dependence of the cyclization rate constant on the solvent properties. At 85°C, the reaction was seven times faster in dioxane k = 5.3 x 10 s ) and was nine times faster in acetonitrile K = 6.93 X 10 s ) than in benzene (k = 7.83 x 10 - s ). The rate constant of the thermal C -C cyclization of enyne-carbodiimides correlates better with the donor properties of the solvent rather than its dielectric constant, which is different from the reactions of enyne-allenes. Therefore, any discussion of the mechanism requires the consideration of alternative routes (Scheme 3.147) [424]. 

Concerning the structure, the cyclopropane derivatives 524—526 deviate from the generally observed cycloadducts of cyclic allenes with monoalkenes (see Scheme 6.97 and many examples in Section 6.3). The difference is caused by the different properties of the diradical intermediates that are most likely to result in the first reaction step. In most cases, the allene subunit is converted in that step into an allyl radical moiety that can cyclize only to give a methylenecyclobutane derivative. However, 5 is converted to a tropenyl-radical entity, which can collapse with the radical center of the side-chain to give a methylenecyclobutane or a cyclopropane derivative. Of these alternatives, the formation of the three-membered ring is kinetically favored and hence 524—526 are the products. The structural relationship between both possible product types is made clear in Scheme 6.107 by the example of the reaction between 5 and styrene. 

The enyne-allene 12 having a methyl substituent at the allenic terminus was likewise prepared from the corresponding enediynyl propargylic alcohol 11 (Scheme 20.4). The presence of a methyl group accelerates the rate of cyclization by approximately sixfold and 12 cyclizes with a half-life of -3.6 min at 78 °C. The formation of a more stable secondary benzylic radical is apparently responsible for the rate enhancement. 

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

Enamine carbaldehyde 76 (Scheme 20) by sequential photochemical cycloaddition and iminium ion-propargylsilane cyclimtion furnishes allenes 77a-c in good yield and with high diastereoselectivity (92X2081). (Gas chromatographic fR values and thin-layer chromatographic Rp values have been reported.) Radical cyclization of ca-iodoalkyl isoquinolone 78a under... 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

The tandem radical cyclization of tetrayne (97) and its derivatives has been performed to generate the polycyclic pyran (98) via a biradical intermediate.238 The cycloaddition reaction of a biradical species (or diyl) and a multiply bonded species (the diylophile)239 has been observed with unique allene diylophiles.240 The short-lived biradical fonned by the irradiation of the diazene (99) is trapped by an allene diester to form a second biradical species (100). Intramolecular cyclization occurs such that all steric interactions are minimized and so enforces stereocontrol in the formation of the cycloadduct (101) see Scheme 14. A paper reports the rearrangement of 2-vinyhnethylenecyclopropane (102) to 3-methylcyclopentene (103) via the triplet biradical (104), which has been characterized for the first tune by IR spectroscopy.241... 

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... 

Allenic hydrocarbons, including cyclic ones, underwent chlorine addition under radical conditions only one double bond reacted [12], A number of conjugated dienes added chlorine in their reaction with (dichloroiodo)benzene under radical conditions. Both 1,2- and 1,4-addition occurred their ratios varied, depending on the substitution of the non-cyclic substrate and the size of the cyclic ones trans products were normally favoured [13]. 1,6-Dienes were cyclized to 1,2-bis chloromethyl cyclopentanes [14] ... 

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