Pyrrolidine hydrogen donor

Nitrogen-containing heterocyclic compounds, including 1,2,3,4-tetrahydroqui-noline, piperidine, pyrrolidine and indoline, are also popular hydrogen donors for the reduction of aldehydes, alkenes, and alkynes [75, 76]. With piperidine as hydrogen donor, the highly reactive 1-piperidene intermediate undergoes trimer-ization or, in the presence of amines, an addition reaction [77]. Pyridine was not observed as a reaction product. 

Visible light irradiation of l,2-dihydro-2-thioxo-l-pyridinyl jV-(4-alkenyl)-A-alkylcarbamates (PTOC carbamates) produces substituted pyrrolidines by a radical chain reaction (see Section 7.2.5.1). In the absence of hydrogen donors, the intermediate pyrrolidinylmethyl radical reacts with the PTOC carbamate itself to afford 2-[(2-pyridinylthio)methyl]pyrrolidines, e.g., 1, 2, 4 and 521,22. On the other hand, in the presence of a good transfer reagent, another functionality can be introduced. In the presence of diphenyl diselenide, the phenylseleno-sub-stituted products were obtained in good yield, e.g., 3 and 622. In every case, however, a low degree of diastereoselectivity of the cyclization products is observed. 

L-Prolinamides (71) with a pendant alcohol act as recoverable bifunctional catalysts of direct nitro-Michael addition of ketones to -nitrostyrenes, giving syn-de s up to 94% and ees up to 80%.204 The pyrrolidine provides enamine catalysis, and the side-chain donors can hydrogen-bond the nitro oxygens. 

One of the best methods for the controlled generation of alkenaminyl radicals is via PTOC carbamates (Section II,E). These precursors react in efficient radical chain reactions with hydrogen atom donors to form amines and pyrrolidines. They are stable to anhydrous acids and, therefore, are suitable precursors for aminium radicals produced by protonation of the first-formed neutral aminyl radical. 

A radical chain reaction initiated by visible light irradiation occurs with l,2-dihydro-2-thioxo-1-pyridinyl 4-alkenylcarbamates (PTOC carbamates) 1 in the presence of a carboxylic acid and a hydrogen-atom donor, preferably tert-butyl mercaptan after homolytic cleavage of the weak N—O bond and a decarboxylation step, the aminyl radical is protonated by the carboxylic acid and cyclizes to give a carbon radical. After reaction with tert-butyl mercaptan and a base the pyrrolidine 2 is obtained. In competition with trapping by tert-butyl mercaptan, or in the absence of this, the carbon radical can react with the PTOC carbamate 1 in a chain-propagating step to give the sulfide 3 (Section 7.2.5.9.)127. 

In the case of the hydrosilylation of C=N bonds, extremely high levels of enantioselectivity were dramatically realized by use of the (tetrahydroinde-nyl)titanium(IV) fluoride T4 (Fig. 12) by Buchwald in 1996 [55]. The in situ catalyst uniquely derived by mixing the titanocene fluoride T4 (1.0-0.02 mol %) with phenylsilane PhSiHj (1.5 eq referred to ketone) as hydrogen atom donor reduces the imines 13-17 (Fig. 13) to the amines A3-A7 in 80-96% yields (Table 3). An alternative activation method for the titanocene by addition of methanol and pyrrolidine was also described. In this case, the imine from acetophenone and methylamine, 13, was converted at room temperature to 35 °C to give the corresponding secondary amine in 94-95% yield with 97-99% ees (S). Moreover, alkylimines were also reduced in 92-99% ees. 

The most widely accepted hypothesis to explain the regio- and stereo outcome of the prolinamide-catalysed aldol reactions supposes the formation of the most stable enamine (generally E-anti) by reaction of the donor carbonyl compound with the pyrrolidine nucleus, and simultaneous activation of the acceptor by hydrogen-bond formation with the carboxamide substituent. Then, the major product is formed by preferential attack of the enamine re-face to the re-face of the carbonyl, as summarised in the ternary complex A (Scheme 6.1). 

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