Atom-transfer cyclization, allylic

Indium trichloride was identified as an efficient catalyst for the atom-transfer cyclization of allylic halides with an alkyne pendant [(42) (43)]. Mechanistic evidence... 

Radical addition to alkenes has been used in cyclizations in aqueous media. Oshima and co-worker studied triethylborane-induced atom-transfer radical cyclization of iodoacetals and iodoacetates in water.121 Radical cyclization of the iodoacetal proceeded smoothly both in aqueous methanol and in water. Atom-transfer radical cyclization of allyl iodoacetate is much more efficient in water than in benzene or hexane. For instance, treatment of allyl iodoacetate with triethylborane in benzene or hexane at room temperature did not yield the desired lactone. In contrast, the compound cyclized much more smoothly in water and yielded the corresponding y-lactone in high yield (Eq. 3.31). 

Parsons and coworkers proved that photochemically induced atom transfer radical cyclization of /V-allyl iodoacetamide 156 proceeded smoothly in the presence of 10 mol% of Mn2(CO)io 153 at room temperature affording 4-iodomethylpyrrolidone... 

Nagashima and colleagues showed subsequently that 5-10 mol% of Pd(PPh3)4 catalyzed atom transfer radical cyclizations (ATRC) of /V-allyl-difluoroiodo-acetamides 158b in fluorescent lab light at ambient temperature [194], Under these conditions, 34—98% yield of cyclized compounds 159b were obtained. No reaction occurred in the dark, while it was considerably slower in the absence of the catalyst. The low yield of 34% in one example (R=Bn) is due to the unfavorable rotational barrier in the substrate, which cannot be influenced by the presence of the catalyst. 

Evidence based on product mixtures now suggests, at least in the cases of a-halocarbonyl and perhaloalkyl starting marterials, that these reactions are in fact atom transfer radical cyclizations (equation 166)324,325. In them, the palladium catalyst is proposed to have roles both as the radical initiator and as a trap for iodine, similar to the more commonly used hexabutylditin. Intramolecular allyl halide-alkyne cyclizations proceed with trans-addition to the triple bond this is evidence that a still different mechanism may be operating in these cases (equation 167)1,326. 

The strong prevalence for allyl radicals to cyclize in 5-exo fashion as well as the accelerating effect of geminal diester substitution was also observed in iodide atom transfer reactions of ally lie iodides. The ratio of S-exo to 6-endo product is even higher than for hydrogen trapping, probably also due to the lower temperature in this photolytically initiated reaction (equation 6). Allylic dimers were again isolated as side products. No... 

The atom transfer radical cyclization of allyl iodoacetate is also more efficient in water than in benzene or hexane. For instance, treatment of the iodoacetate with triethylborane in benzene or hexane did not give any desired lactone while in water the reaction proceeds with high yield.It is suggested that the large... 

Investigations by both Katsuki and Che have highlighted the application of chiral Mn(III) salen complexes for asymmetric N-atom transfer reactions (Fig. 17) [79-81]. In the former case, the use of [Mn(salen)PF6] together with PhI= Ts affords modest product yields and enantiomeric ratios for amination of simple benzylic and allylic starting materials. A high-valent Mn imido species is presumed to be the active oxidant. Methodological and mechanistic studies conducted by Che have found that the same types of Mn(III) salen complexes will induce oxidative cyclization of sulfamate esters. Although these catalysts afford... 

The EtsB-induced halogen atom transfer radical cyclization reaction is a successful application. Cyclization of iodo acetal 44 afforded the tetrahydrofuran derivative 45 in almost quantitative yield (Scheme 26) [32]. Et3B also induced radical cyclization of A -allylic a-iodoacetamide to give y9-iodomethyl-y-lactam via an atom transfer process [34]. The reaction of 46 prepared from 2-prolinol proceeded smoothly within 10 min in boiling benzene in the presence of Et3B to yield IR, 8S)-... 

Scheme 27. Atom transfer radical cyclization of A-allylic iodoacetamide...

Et3B-induced atom transfer radical cyclization of allyl iodoacetate (54) proceeded much more smoothly in water at ambient temperature than in benzene or hexane... 

But before 1980, the foundations for essentially all modern synthetic radical reactions had been laid, sometimes by synthetic organic chemists but more often by physical organic chemists. Kharasch reactions (now often called atom transfer reactions) were known since the 1930s and 1940s, and tributyltin hydride was introduced in the 1960s. In the 1970s, SnAc reactions and redox chain aromatic substitutions (Minisci reactions) were already topical, and allylations with allyl-tributylstannane were first described. In short, there were a number of ways to generate and trap radicals on the one hand, and a number of fundamental transformations of radicals such as addition and cyclization to multiple bonds on the... 

CycBzation. Cyclization of iV-allyl a-bromoamides induced by ligated CuBr room temperature involves atom transfer. 2-Pyridylformaldimines are better ligands than 2,2 -bipyridine. 

The reaction mechanism has tJso been investigated by DFT calculations, lending support for the stepwise mechanism [111, 112]. The first key intermediate is the diruthenium nitrenoid species (S = 1/2). In the transition state of the C-H bond scission, the coordinated nitrenoid interacts with the allylic H atom, polarizing the C-H bond. Subsequent H atom transfer to the N atom generates a diradical species comprising a diruthenium amide tethered to an allylic radical (S = 3/2). Of interest, the unpaired electrons are primarily localized at the two Ru centers (and the allylic fragment), with litde spin density (0.14) at the N atom. Finally, radical rebound forms the cyclized amine. 

Scheme 232 Sequential allylic amidation and atom-transfer radical cyclization.

Atom-transfer radical cyclization (ATRC) is an atom-economical method for the formation of cyclic compounds, which proceeds under mild conditions and exhibits broad functional group tolerance. Okamura and Onitsuka described a planar-chiral Cp-Ru complex 124-catalyzed asymmetric auto-tandem allylic amidation/ATRC reaction in 2013. This protocol proceeds highly regio, diastereo, and enantioselec-tively to construct optically active y-lactams from readily available substrates in a one-pot manner (Scheme 2.32). In this process, a characteristic redox property of ruthenium complexes would work expediently in different types of catalyzes involving mechanistically distinct allylic substitutions (Ru /Ru ) and atom-transfer radical cyclizations (Ru /Ru ), thus leading to the present asymmetric auto-tandem reaction [48]. 

Finally, isolated reports on the ability of NHC-Cu complexes to catalyze diverse organic transformations can be found throughout the literature and notably include heterocycles synthesis, atom-transfer radical cyclization leading to chloronaphthalenes, and allylation reactions using [(IPr)CuFj and an allylsiloxane. An increasing number of studies involving the use of CO2 with NHC-Cu catalysts has also been reported lately, they encompass... 

Following Yang s report, the atom-transfer radical cyclization reaction of 58 provided chiral cyclopentane ring 59. The bromide of 59 was removed by radical dehalogenation reaction to produce 60. Wittig olefination followed by reduction of the ester group gave chiral alcohol 62 that could be easily converted into the allylic alcohol 57 (Scheme 17). 

This researeh was extended to include non-symmetrical amidinate complexes of the same type with mixed Cp and Cp ligands, such as the cationic species [Cp Ru 2-PrN=C(Me)NPr )RuCp(L)] (138 L = none, NCMe, CNBu , PMc3 BF4 salts). For 138 (L = CNBu ), there is NMR evidence that the isonitrile ligand switches between the ruthenium centers. Coordinatively unsaturated intermediates play a key role in catalytic processes, and thus complexes 138 (L = none PFe salt) and 135 (PFe salt) were found to catalyze the atom-transfer radical cyclization of A7-allyl trichloroacetamides. It was discovered that the greater protection offered by the steric bulk of the Cp" ligand led to the superior performance of 135 (PF salt). ... 

Finally, there is a rather limited number of reports in the literature on the ability of NHC-Cu complexes to catalyze diverse organic transformations. These include the synthesis of heteroeyeles, A -eouplings, atom-transfer radical cyclizations to produce chloronaphthalenes, 1,3-halogen migrations and allylations using [(IPr)CuF] in the presence of an allylsiloxane. ... 

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