Oxidative radical cyclization

Oxidative radical cyclization of fi-keto esters. Radical cyclizations of unsaturated 0-keto esters initiated by Mn(III) acetate (1) can be terminated by oxidative 0-hydride elimination by Cu(OAc)2 (equation I). This radical reaction can... 

Phenylhydrazones of /i-stannyl ketones undergo oxidative radical cyclization to afford azocyclopropanes upon treatment with an oxidizing agent such as DDQ, Pb(OAc)4 and NBS (equation 27)43. 

Fig. 83 Copper(II)-catalyzed oxidative radical cyclizations of malonamides or cyanoacetamides...

The oxidative radical cyclization of o-alkyl and o-arylbenzoic acids by BTI and iodine, photochemically, was a good way to prepare y- and 5-lactones from these acids. The experimental conditions were similar to those mentioned in the previous Section but milder, since no heating was required and the amount of iodine was 0.1 equiv. in respect to BTI. In the following example, a small amount of an iodinated 5-lactone was also formed [70] ... 

In this sequence, NO3 can formally be regarded as a synthon for O atoms in solution. Because the released NOa is a comparatively stable radical that does not initiate a radical chain process under the applied reaction conditions, this sequence is termed a self-terminating oxidative radical cyclization —the cascade-initiating radical contains the unreactive leaving group that is released in the final step of the reaction. In contrast to reactions performed under classical radical chain conditions and that are nearly always associated with a loss in overall functionality of the molecule, in self-terminating radical cyclizations the net amount of functional groups is retained in the system. 

Lee et al. developed a new method for the construction of the skeleton of HA via the Mn(III)-mediated oxidative radical cyclization of allylic compound 16 derived from 2. The thermodynamically unstable exo double bond product 17 could be easily isomerized to the endo olefin 18 by treating it with triflic acid as reported in the literature (Scheme 4-9). ° ... 

Two syntheses of the urmatural (- )-enantiomer of monomorine I (e r-427) end this section. The approach of Artis et al. hinged on the oxidative radical cyclization of iodoalkyl pyrrole 484, made in seven steps ca. 28% yield) from (/ )-... 

A recently reported synthesis of (-l-)-triptophenolide illustrates the utility of this auxiliary in radical reactions [37]. The key step in the synthesis, outlined in Fig. 6, is a lanthanide triflate-promoted oxidative radical cyclization of an 8-phenylmenthyl keto ester mediated by Mn(OAc)3. The product of the radical cyclization is formed in excellent yield and selectivity in the presence of ytterbium triflate. The Lewis acid presumably locks the p keto ester in a syn orientation. The configuration of the transformation can be understood based upon a transition state arrangement as shown in 36. 

Phenylmenthol was also used by Yang et al. in an Mn -based oxidative radical cyclization reaction catalyzed by Ln(OTf)3 (lanthanide triflate) [44]. With the achiral substrate (R = Me), the cyclization reaction was very slow in... 

Heterocyclization. Cyclization of ally lie carbamates to oxazolidin-2-ones via oxidative radical cyclization. Hydrogen comes from THF. 

Diels-Alder reactions. The cycloaddition of 1,3-cyclohexadiene with electron-deficient dienophiles is promoted by the dihydrate of YbfOTf), under high pressure. Radical cyclization. The dehydroabietane skeleton is readily formed by an oxidative radical cyclization reaction to which a catalytic amount of YbfOTf) dihydrate is also added. 

The oxidative radical cyclizations of l-(co-bromoalkyl)-3-acetylpyrroles 29 (n=l-3) were found to occur predominantly at the adjacent C-2 position to afford the [l,2-a]-fused pyrroles 30 <97TL7937>. Similar cyclizations of pyrrole-2-carbaldehydes were found to react at the opposite a-position. 

Oxidative radical cyclization sequences have also been used to generate 1,2-fused indoles. Treatment of amides 152 and 154 with dimethyl methylmalonate in the presence of manganese(III) acetate and sodium acetate in acetic acid, gave the expected cyclized product in 63% and 40%, respectively [97]. The proposed mechanistic sequence involves the intermolecular addition of the dimethyl methylmalonate radical to the tethered exocyclic alkene followed by cyclization and finally rearomatization. Byers and coworkers also achieved a similar cyclization on the C-2 position of the indole when a 3-acylindole was subjected to these oxidative cyclization conditions. 

Chikaoka S, Toyao A, Ogasawara M, Tamura O, Ishibashi H (2003) Mn(III)/Cu(II)-Mediated Oxidative Radical Cyclization of a-(Methylthio)acetamides Leading to Erythrinanes. J Org Chem 68 312... 

In Cramer s [60] heteroatom-nucleophile-induced C-C fragmentations, an allenic hydroxamic acid 162 was employed for a domino oxidative radical cyclization to afford the densely functionalized 1,2-oxazine 166 in 52% yield... 

Another important feature is the oxidative radical cyclization of a polyene chain to give a sLx-manbaed ring this reaction proceeds with high stereoselectivity through chair transition states [100]. Thus, cyclization mediated by Mn is a powerful approach for the synthesis of benzo-fused polycyclic natural products, such as 123 from 122 (Eq. 9.24) ... 

A new mode of oxidative organocatalytic activation has been reported, termed organo-SOMO catalysis, which has been successfully applied using an enantioselective intramolecular a-arylation of aldehydes via catalytic oxidative radical cyclization (Eq. 9.25) [101]. In this approach, the exposure of an aryl-tethered aldehyde (124) to a chiral secondary amine catalyst 125 and a suitable oxidant leads to enantio-enriched 126 ... 

The reaction of A-arylacrylamides and simple alcohols in the presence of 70% aqueous solution of TBHP leads to metal-free synthesis of 3,3-disubstituted oxindoles. A series of hydroxyl-containing oxindole derivatives could be prepared using this method. The reaction is proposed to proceed through an oxidative radical cyclization mechanism and shows excellent functional group tolerance." ... 

Oxidative radical cyclization of various substituted a-methylthioacetamides has been facilitated by Cu(OAc)2 in the presence of Mn(OAc)3 (eq 30). Although the reaction proceeded to some extend with Cu(OAc)2 alone, the omission of Mn(OAc)3 led to considerably lower yields of the desired product(s). ... 

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