Hydrogen abstraction-cyclization process

Formations of Cyclic and Spiro Acetals by a Tandem Intramolecular Hydrogen Abstraction-Cyclization Process (Schemes 30 through 36)... 

A systematic study for the system depicted in Eq. (39.1) has demonstrated that rate constants k for 1,5-hydrogen transfers are between 5 x 10 s (X,Y = Me,H) and > 10 s (X,Y = S(CH2)3S) [136]. Hydrogen abstraction from a methyl group (X,Y = H,H) does not occur readily ( 15 < 10 s ). Consequently, highly efficient hydrogen transfer-cyclization processes are possible only when stabilized intermediate radicals are generated. 

The presence of heteroatoms in the N-alkyl chain can significantly affect the cyclization process. Benzylic hydrogen abstraction is preferred, for... 

Coumestrol has been prepared via a photocyclization of the glyoxylate ester shown below through consecutive 5-hydrogen abstraction and cyclization processes, and is followed by... 

Scheme 29 describes a plausible mechanism for the formation of the products which fit the observed coulometric (n 0.45 F/mol) and preparative results. The intramolecular cyclization process involves a dimerization between a radical cation 52a and the ketene imine 52 to form the intermediate radical cation 52b which then cyclizes to the radical 52c which can abstract a hydrogen atom leading to 54 or can be further oxidized and transformed through a cyclization and deprotonation reaction to 53 which involves 1 F/mol. However, it seems that the [2 -1- 3]-cycloaddition between the parent compound 52 and the cation 52d giving rise to 55 is the fastest reaction as compared with the intramolecular cyclization of 52d to 53. This can also explain the low consumption of electricity. 

A-Chloro-Af-methoxy-Af -arylureas (84) have been reported to cyclize in good yield to 2-benzimidazolinones (85) upon treatment with NaH. Af -Alkylation prevented the reaction and the process involves anilide formation by hydrogen abstraction and an intramolecular Sat2 displacement of chlorine by the electron-rich ortho carbon (equation 11) . ... 

The arachidonic acid cascade is a biological free radical oxidation of unsaturated fatty acids leading to formation of the prostaglandins (equation 102). Cyclization of a peroxy radical intermediate 66 leading to endoperoxide 67 was proposed as a pathway for this process, and this was demonstrated in chemical model systems, in which the peroxyl radical 66 was generated by hydrogen abstraction from the hydroperoxide corresponding to 66. 

Hydrogen abstraction can occur from a position within the ketone molecule, and this generates a biradical that may cyclize by combination of the radical centres. The overall photocydization process is observed for a wide variety of compound types, and it has been used extensively to make cyclic or polycyclic systems, in an unconstrained system a ketone (n,n ) excited state shows a preference tor abstraction from the y-position (4.42), which can be understood on... 

Although all the products can be rationalized on the basis of 7-hydrogen abstraction followed by cyclization or rearrangement-cyclization of 1,4-biradical intermediates, the mechanism has been shown to involve analogous zwitterionic intermediates [299b, 301], Although they are not strictly Norrish II reactions, transformations of 98 will be considered so for the purposes of discussion since the photoproducts and the mechanisms of their formation are very similar to those expected of Norrish II processes. 

The corresponding photocyclization of S-arylvinyl sulfides to dihydro-thiophens has been shown to proceed via short-lived thiocarbonyl ylide intermediates, formed in turn by cyclization of triplet excited states. 1-Phenylthio-3,4-dihydronaphthalene (49), for example, affords the colored thiocarbonyl ylide (50)44 the isolated products are derived by processes involving hydrogen abstraction and migration. The greater efficiency of the photocyclization of 2-thioaryloxyenones (51) to dihydrothiophens (52) has been attributed to the additional stabilization afforded to the ylide (53) by the carbonyl group.45 Other similar photocyclizations have been reported.46... 

There are four distinct processes initiated by y-hydrogen abstraction in excited carbonyl compounds Norrish type II photoelimination, Yang photo-cyclization (cyclobutanol formation), Yang photoenolization (o-xylylenol formation), and (3-cleavage of radicals from carbons adjacent to the radical sites of the 1,4-biradicals. Some of these require unique structures and generate distinct products. 

Two other examples of the synthesis of bicyclic compounds whose skeleton consists only of carbon atoms are shown in Sch. 24, each of them is instructive in its own way. Upon irradiation of the cyclohexane derivative 65, not the expected product from a hydrogen abstraction from the allylic position, but the bicyclo[3.3.1]heptane 67 was obtained by cyclization of the less stable biradical 66-B [57]. The reason for this is the exclusive hydrogen back-transfer of the more stable biradical and it underlines the importance of this process in regioselectivity phenomena of the Norrish-Yang reaction. 

Tandem reactions may also occur by initial allylic hydrogen abstraction (with 1,5-hydrogen transfer) by a vinylic radical, followed by a cyclization process. This methodology has been used to synthesize bicyclic and tricyclic systems (equations 135 and 136)778,793,807-809. Electron-withdrawing groups conjugated to the vinylic halide increase the yields and decrease reaction times considerably. 

In the absence of 7-hydrogen, other intramolecular hydrogen abstraction processes can become competitive. For example, a highly diastereoselective pho-tocyclization to cw-3-hydroxyproline derivatives is observed with substituted N-(2-benzoylethyl)-N-tosylglycine esters 155. The products 156-157 involve a 8-hydrogen abstraction by the excited carbonyl and a cyclization of the 1,5-biradical intermediate. In the presence of a (3-substituent, a high asymmetric induction is observed. The observed selectivity can be deduced from the preferred conforma-... 

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