Radicals from PTOC carbamates

C. Dialkyl Aminium Cation Radicals from PTOC Carbamates. 23... 

Lewis Acid Complexed Aminyl Radicals from PTOC Carbamates.. .. 29... 

The mechanism of aminyl radical generation from PTOC carbamates follows closely the radical chain mechanism of alkyl radical generation from PTOC esters. The chain reaction sequence involves the series of steps shown in Scheme 8. Several methods for inducing N —O bond cleavage are possible. Photochemical decomposition of 29 via visible light irradiation is used to initiate the chain reaction sequence at ambient or subambient temperature reactions have been run as low as -78°C (91TL6493). 

A variety of alkaloid skeletons can be prepared from 5-exo cyclizations of aminium cation radicals derived from PTOC carbamates, and some are listed in Table VI (90T2329). Perhydroindoles (entry 1), 1-, 2-, and 3-substituted pyrrolizidines (entry 2-4), tropanes (entry 5), and other pyrrolidine containing ring systems were obtained in 50-96% yields. Direct com-... 

Intermolecular addition and addition-cyclization reactions of aminium cation radicals with electron-rich alkenes such as ethyl vinyl ether (EVE) allow an entry into products containing the N—C—C—O moiety of 13-amino ethers 70 or the equivalent of /3-amino aldehydes 71. The mild conditions under which aminium cation radicals are generated from PTOC carbamates makes the reactions described in Scheme 22 possible. In the absence of hydrogen atom donors, the /3-amino ethoxy(2-pyridylthio) acetal 71 was the major product. The mixed acetal can easily be converted... 

Monoalkyl aminium radicals cannot be prepared from PTOC carbamates 29 due to an equilibrium in solution favoring 2-mercaptopyridine-Ar-oxide and an alkyl isocyanate [Eq.(ll)]. With Af-(monoalkyl)thiazole-2-thione carbamates, TTOC carbamates, the equilibrium lies far to the side of the carbamate 84, and these precursors can be prepared from an isocyanate and Ar-hydroxythiazole-2-thione [Eq. (12)]. Under UV photoinitiation in acidic media, TTOC carbamates are efficient precursors for monoalkyl aminium cation radicals (Scheme 26). Monoalkylaminium radical 85 ey-clizes as efficiently as its analogous dialkylaminium radical 66, and the resulting carbon radical 86 can be trapped by a variety of radicophiles (91JOC1309) to prepare substituted pyrrolidines. 

A wide application of Newcomb s method provides a variety of N-heterocyc-lic systems, such as perhydroindoles, pyrrolizidines and aza-brigded bicycles [59, W, 146], The mild reaction conditions are compatible with several funtional groups of the substrate and several trapping agents to functionalize the cyclized product. 2-Substituted pyrrolizidines 132 are accessible by tandem cyclization of iV-allyl-substituted PTOC carbamate 131. In this case the allyl group on the nitrogen serves as an internal trap for the intermediate carbon radical. The Af-methylcyclohept-4-enaminium radical cation, produced from the corres-... 

C. Amidyl Radicals from A-Acyl-A-alkyl PTOC Carbamates. 40... 

The PTOC carbamate method for efficient and controlled generation of aminyl radicals allows kinetic studies that previously were not possible with tetrazene precursors. As is the case with carbon radicals, optimum synthetic utility of chain reaction sequences is found when absolute rate constants or ratios of rate constants for competing reactions are known, i.e., Scheme 8, step D vs step E. If an absolute rate constant is known for one reaction, then other absolute rate constants can be determined for other reactions from the product distributions in competitions of the reactions of interest with the reaction with a known rate constant. 

The acid is also a critical factor. Acetic acid does not appear to protonate an aminyl radical completely even in acetonitrile. Under highly acidic conditions, the PTOC carbamate may be protonated as was indicated in a study of the simple (V,/V-dipropyl PTOC carbamate. In neat trifluoroace-tic acid (TFA), the long wavelength absorbance responsible for the yellow color of the precursor completely disappeared, presumably from protonation at the thione sulfur to form the thiol cation 68 (Scheme 19). The yellow PTOC carbamate was recovered upon neutralization of the TFA... 

Newcomb and coworkers have very elegantly demonstrated that N-hydroxypyridine-2-thione carbamates lc (PTOC carbamates, X = NR2) are directly analogous to the A-hydroxy-pyridine-2-thione esters la. They can be prepared readily from primary and secondary amines. Reaction of these carbamates in a radical chain process gives carbamoyl radicals that decarboxylate to give aminyl radicals, Scheme 40.66 71 In the... 

Surprisingly, however, monoalkylaminium cation radicals 104 have not been studied well. Newcomb found that they could not be prepared from respective PTOC carbamates due to instability of the precursors, nevertheless, the problem was solved via the isocyanate condensation with a different thio-hydroxamic acid 105a, as shown in Scheme 44. These deriva-... 

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