Enantioselective atom-transfer

Ruthenium complexes are capable of catalyzing halogen atom transfer reactions to olefins. This has been illustrated in the enantioselective atom transfer reactions of alkane and arene-sulfonyl chlorides and bro-motrichloromethanes to olefins using chiral ruthenium complexes. Moderate ee s up to 40% can be achieved for these transformations [74-77]. These specific reactions are believed to follow a radical redox transfer chain process. 

Chiral Lewis acid promoted atom transfer reaction (Kharasch reaction) of a-halo oxazolidinone imide 90 and 1-octene 92 has been reported by Porter et al. (Scheme 23) [78]. The enantioselective atom transfer utilizing Zn(OTf)2 and phenyl bisoxazoline ligand 93 as a chiral Lewis acid. The yields of the products, however, were quite low ranging from 5-15% and only moderate enantioselectivities were achieved (up to 40%). 

Highly enantioselective atom transfer radical cydization reactions catalyzed by chiral Lewis acids have been reported by Yang et al. [80]. Two main advantages of these enantioselective cyclizations include installing multiple chiral centers and retaining a halogen atom in the product, which allows for further functionalization. 

We first tested enantioselective introduction of the isopropyl group and methyl group using the highly enantioselective atom-transfer radical cycliza-... 

Yang D, Gu S, Yan YL, Zhu NY, Cheung KK. Highly enantioselective atom-transfer radical cychzation reactions catalyzed by cbiral Lewis acids. J. Am. Chem. Soc. 2001 123 (35) 8612-8613. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

In this chapter, metal-mediated asymmetric oxygen-, nitrogen-, and carbon-atom transfer reactions were described. The substrates were limited to olefins. Owing to limited space, examples of the reactions were collected with the priority given to enantioselectivity, except for some germinal... 

Fig. 31.17 (a) Experimental observation of dihydrides in the PHOXIr+ system by NMR (S = THF). (b) The DFT-derived mechanism for Ir-catalyzed enantioselective hydrogenation involving the sequential addition of two molecules of dihydrogen, with a single H-atom transfer from each one (S = CH2CI2). 

Radical chemistry has seen tremendous progress in the past two decades and can now be considered as an eminent sub discipline in synthetic organic chemistry [1-6]. Diastereoselective radical chemistry is well established and many examples of enantioselective radical reactions have appeared in the recent literature. For reviews on diastereoselective radical chemistry see [7-11] for reviews on enantioselective radical chemistry see [12-16] and for reviews on conjugate additions, see [17,18]. This review will detail different ways to introduce asymmetry during a radical reaction. These transformations can be broadly classified into atom transfer reactions, reductive alkylations, fragmentations, addition and trapping experiments, and electron transfer reactions. 

Hydrogen atom transfer implies the transfer of hydrogen atoms from the chain carrier, which is the stereo-determining step in enantioselective hydrogen atom transfer reactions. These reactions are often employed as a functional group interconversion step in the synthesis of many natural products wherein an alkyl iodide or alkyl bromide is converted into an alkane, which, in simple terms, is defined as reduction [ 19,20 ]. Most of these reactions can be classified as diastereoselective in that the selectivity arises from the substrate. Enantioselective H-atom transfer reactions can be performed in two distinct ways (1) by H-atom transfer from an achiral reductant to a radical complexed to a chiral source or alternatively (2) by H-atom transfer from a chiral reductant to a radical. 

Scheme 6 Sultam templates in enantioselective H-atom transfer...

Scheme 7 Enantioselective hydrogen atom transfer to sulfones...

Enantioselective synthesis of /1-amino acids is important as they are present in various natural products and in many biologically active compounds [26,27]. Several methods exist for the enantioselective synthesis of -substituted /1-amino acids (/l3-amino acids) however, synthesis of a-substituted /1-amino acids (/l2-amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize /l2-amino acids (Scheme 9) has recently been described [30]. 

An interesting intramolecular radical cyclization followed by enantioselective hydrogen atom transfer has recently been reported (Scheme 11) [40]. This reaction is carried out in the presence of a chiral complexing agent 38, which... 

Scheme 11 Enantioselective H-atom transfer reaction with hydrogen bonding catalyst... 

Scheme 24 shows the atom transfer radical cyclizations of unsaturated /3-keto esters 94 using MgfCKLh and chiral ligand 96. It was found that toluene as a solvent generally gave higher enantioselectivities than CH2CI2... 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

Asymmetric amidation of sp C—H bonds was reported in good yields and moderate enantioselectivities (Scheme 5.27)." ° When benzylic or allylic C—H bonds were used, similar results were also obtained." In these reactions the prepared nitrenes, PhI=NTs, and/or PhI(OAc)2+NH2Ts were used as nitrogen atom transfer sources. The studies showed that Ru=NTs was formed in situ and acted as a possible active intermediate when a ruthenium catalyst was used (Figure 5.12), whereas a radical intermediate might be involved when a manganese catalyst was used. 

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