Amines free radical-mediated

DKR of Amines by Biocatalysis and In Situ Free-radical-mediated Racemization 153... 

Gastaldi, S., Escoubet, S., Vanthuyne, N., Gil, G. and Bertrand, M.P., Dynamic kinetic resolution of amines involving biocatalysis and in situ free radical mediated racemization. Org. Lett., 2007, 9, 837-839. 

Viswanathan R, Prabhakaran EN, Plotkin MA, Johnston JN (2003) Free radical-mediated aryl amination and its use in a convergent 3-1-2 strategy for enantioselective indoline alpha-amino acid synthesis. J Am Chem Soc 125 163-168... 

Prabhakaran EN, Nugent BM, Williams AL, Nailor KE, Johnston JN (2002) Free radical-mediated vinyl amination access to N, N-diaDcyl enamines and their beta-staimyl and beta-thio derivatives. Org Lett 4 4197-4200... 

Pigza, J. A., Han, J. S., Chandra, A., Mutnick, D., Pink, M., Johnston, J. N. (2013). Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a p-Stannyl Enamine Linchpin. 

During the time frame covered by this chapter, stannanes have been reported to have been involved in radical chemistry not involving the more traditional functionalities. For example, Marzi and coworkers reported that the reduction of cyclic thionocarbonates (e.g. 82) with BusSnH under standard radical conditions affords cyclic acetals that can then be further transformed into 1,2-diols (equation 57)219. This transformation represents a new approach to the protection of these diols. Zehl and Cech described the use of Bu3SnH in the reduction of azide (83) to the corresponding amine (equation 58)305, while Hanessian and his associates reported the Ph3SnH-mediated free-radical reduction of the tertiary oxalate (84) (equation 59)309. This transformation represents a departure from the more typical reduction of a pyridinethioneoxycarbonyl (PTOC) oxalate ester321. 

Reversible hydrogen abstraction from a stereogenic centre adjacent to an amino group will result in a free radical which can then racemize to give either (R)- or (S)-amine depending on the biocatalyst used for the DKR. CALB mediates the preparation of (R)-amide while alkahne protease mediates the (S)-amide [59, 60). 

In the mid-1980s, the first technique that relies on the reversible termination of radicals with a stable free radical was developed in the group of E. Rizzardo at CSIRO in Australia. Rizzardo and co-workers found that nitroxide-stable free radicals were able to add to carbon-centered radicals to form alkoxy amines (9). In certain cases these alkoxy amines are thermally unstable, so that they enter into an equilibrium between (transient) carbon-centered radical and (persistent) nitroxide radical on one side, and alkoxy amine on the other side. TEMPO was initially the most frequently used nitroxide in conjunction with the polymerization of styrene and its derivatives. The TEMPO-polystyrene adduct requires temperatures of 120° C or above in order to establish an equilibrium at which polymerization takes place. Around the mid-1990s Georges and co-workers focused on the TEMPO-mediated pol5unerization of styrene (10), and developed various strategies to overcome intrinsic weaknesses of the system. They used camphor sulfonic acid to enhance the rate of polymerization (11). This rate enhancement was later elucidated to be due to the destruction of excess nitroxide that builds up during the polymerization. 

More recently controlled free radical polymerization methodologies have been employed for the preparation of novel smart AB diblock copolsrmers. Nitroxide-mediated polymerization was utilized for the synthesis of sodiiun 4-styrenesulfonate-block-sodium 4-vinylbenzoate block copolymer (133). These strong acid/weak acid species exhibit reversible pH-induced self-assembly, with the sodium 4-styrenesulfonate residues remaining ionized and thns permanently hydrophilic over the useful pH range whereas the sodium 4-vinylbenzoate block can be reversible protonated (the carboxylate residue has a pa s 4.0). The same block polymers can also be prepared via RAFT, albeit with somewhat more control. Other workers reported the preparation of such AB diblock copolymers as well as some analogous amine-based styrenic diblock copolymers, (48) shown in Figure 54. 

TEMPO is widely used as a radical trap, as a structural probe for biological systems in conjunction with EPR spectroscopy, as a reagent in organic synthesis, and as a mediator in controlled free radical polymerisation. As well as alcohol oxidation, TEMPO also finds use in the oxidation of other functional groups, including amines, phosphines, phenols, anilines, sulfides and organometallic compounds [144]. 

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