Chiral nitroxide radicals

Preparation of chiral nitroxide radicals is important because of their potential as molecules with unique optoelectronic properties. The radical enolate 151 was generated from 150 on treatment with samarium(II) diiodide at low temperatures [95JOC6820]. The intermediate enolate was acylated to provide the stable free radical 152 in good yield. 

A purely organic chiral nitroxide which shows liquid crystalline behaviour as well as intriguing magnetic properties and a dependence on the enantiomeric nature has been reported [180]. The reason for studying the compounds was to increase the sensitivity of mesophases to magnetic and electric fields. The racemic modification of the radical, which displays a nematic phase, proved to be more sensitive to alignment than the cholesteric phase with the enantiomers present. It was proposed that the compounds may also be used to study the dynamic nature of mesophases by electron paramagnetic resonance spectroscopy. 

Finally, chiral nitroxyl radicals can be synthesized by the intramolecular coupling of enones with nitro compounds under reductive conditions [109]. Thus reaction of appropriately substituted nitro enones with Sml2, followed by a quench with reactive acyl chloride electrophiles, provides a-asymmetric nitroxide radicals in excellent yields (Eq. 97). 

Stereoselective Trapping of Prochiral Radicals with Chiral Nitroxides... 

Prochiral carbon radicals have enantiotopic faces reaction with chiral nitroxides can result in two possible diastereomeric products (Scheme 9). Our laboratory has been investigating the ability of chiral nitroxides to differentiate between the two enantiotopic faces of a transient prochiral carbon radical. In many of the examples, the prochiral radical is generated by the lead dioxide oxidation of a secondary benzylic hydrazine. Early work utilized a camphor-derived nitroxide 27, which was coupled to a secondary benzylic prochiral carbon radical with low but reproducible stereoselectivity (Scheme 10) [26]. The stereoselectivity jumped dramatically upon moving to a conformationally rigid nitroxide in the form of the steroid doxyl radical... 

Scheme 9. Reaction of a chiral nitroxide with the enantiotopic faces of a prochiral radical...

Thus other chiral nitroxides were developed to probe the stereoselective coupling reaction. Two conformationally rigid doxyl nitroxides prepared from camphene, camphoxyl nitroxides 29, were synthesized and coupled to several prochiral carbon radicals. In this series, the results were disappointing very low diastereoselectivities were obtained (Scheme 11) [27]. 

A question that continually arises when the topic of stable free radical copolymerization is discussed is what is the composition and microstructure of the copolymers Scheme 1 shows the four possible propagation reactions for a stable free radical copolymerization based on the terminal model. It is expected that if in the uncapped form, the nitroxide leaves the vicinity of the propagating chain end the copolymer microstructure should not be affected by the presence of nitroxide. Unsuccessful attempts by Sogah and Puts to influence the microstructure of polymers prepared by the SFRP process using chiral nitroxides suggest that the nitroxide does leave the vicinity of the propagating chain end (3). This is in agreement with Fukuda s results, which show that the microstructure of styrene-acrylonitrile (SAN) copolymers... 

Minguet. M. Amabilino, D.B. Wurst, K. Veciana, J. Circular dichroism studies of crystalline chiral and achiral a-nitronyl nitroxide radicals in KBr matrix. J. Chem. Soc., Perkin Trans. 2 2001, (5), 670-676. 

DFT calculations at UB3LYP/6-31G(d,p), /6-31+G(d) or 6-31G-b(d,p) level and spectrometry analysis of enantioselective chiral amine-catalysed olefin epoxidation by H2O2 or oxone in MeCN-H20 (95 5) in the presence of NaHCOj suggest that the amine is first oxidized to nitroxide radical which is further oxidized to A,A(-dioxo-radical which is the effective oxidant for epoxide formation. The calculations also explain the formation of a large amount of diol during the epoxidation reaction A(,A(-dioxo-radical is protonated by HC03, and this protonated radical easily oxidizes olefin into diol. Pyridine suppresses the formation of diol because it suppresses the protonation of tV,tV-dioxo-radical." ... 

Ananchenko G, Matjgaszewski K. Controlled/living radical polymerization of tert-butyl acrylate mediated by chiral nitroxides. A stereochemical study. Macromolecules. 2002 35 8323-8329. 

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

A similar approach was followed with the eROP of 4-MeCL, followed by nitroxide mediated living free radical polymersation (NMP) of styrene using a bifunctional catalyst (Scheme 11.18) [62]. Styrene, the monomer for the NMP, was added already at the beginning since it proved to be a good solvent for the eROP of lactones. At low temperatures, no radical polymerization occurs thus the two polymerization mechanisms are thermally separated. When the eROP reached a conversion of 50%, a lipase inhibitor, paraoxon, was added to the reaction mixture to prevent further incorporation of the undesired enantiomer. Increasing the temperature to 95 °C started the nitroxide mediated LFRP, to afford block copolymers. After precipitation, the chiral block copolymers obtained showed two Tg s at-51 °C and 106 °C. The specific rotation [a]D25 of the block copolymer was -2.6°. 

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