Asymmetric radicals

Despite the usual loss of optical activity noted above, asymmetric radicals can be prepared in some cases. For example, asymmetric nitroxide radicals are known. An anomeric effect was observed in alkoxy radical (31), where the ratio of 31a/31b was 1 1.78. ... 

Mg11 complexes are also effective for controlling asymmetric radical reactions.33,34 Moreover, enantioselective radical reactions using chiral Mg11 complexes have been studied, and high enantioselectivities have been realized in the presence of stoichiometric or catalytic amounts of chiral auxiliaries such as bis-oxazolines (Scheme 8).35-39 In most cases, substrates having bidentate chelating moieties are required. 

The asymmetric radical alkylation was briefly mentioned in Section 8.06.6.6. It is shown in Equation (56) and gives the products in over 98% diastereomeric excess <2003CC426>. 

Asymmetric radical reactions. Curran et al,3 report several asymmetric reactions of radicals derived from Oppolzer s camphorsultam. Thus the reaction of the iodosultam 1 with allyltributyltin initiated by triethylborane provides an epimeric... 

Asymmetric radical reactions. Several groups have reported asymmetric radical reactions observed with (S,S)- or (R,R)-1 as the chiral auxiliary. Thus the iodide 2 in the presence of BuySnH and AIBN cyclizes mainly to two diastereomeric endo-cyclic products 3 in the ratio 14 1.2... 

New methods for the preparation of germanes and stannanes reported since 1995 are dealt with in Section n. In Section III, radical chain chemistry involving trialkyltin hydrides is examined. In particular, the synthetic utility of tributyltin hydride will be reviewed, as well as that of other stannanes. Recent advances in the area of asymmetric radical chemistry involving chiral non-racemic stannanes are also included. Section IV details a limited number of examples of non-radical stannane chemistry, while Section V covers recent advances in germane and plumbane chemistry. While we have restricted ourselves largely to the literature since the beginning of 1996, some salient features of earlier work are included when relevant to the discussion. 

Akaboshi M, Noda M, Kawai K et al (1979) Asymmetrical radical formation in d- and L-alanines irradiated with yttrium-90 P-rays. Orig Life Evol Biosph 9 181-186... 

Although there exist numerous ground state reactions, photochemically induci asymmetric radical additions can be very efficient and even highly stereoselectr [125]. Furthermore, no particular functionalization of the starting material is n< essary prior to the formation of a C-C bond. In this context, the photosensiti addition of alcohols, cyclic acetals, and tertiary amines to electron-deficient kenes has been particularly studied. This will be illustrated by a few exampli First attempts to induce chirality in the photoinduced addition of ket radicals (e.g., U) involved a, 3-usaturated carbonyl compounds such as 208 rived from carbohydrates (Scheme 56) [126]. With benzophenone as sensitizi these radicals could be added stereoselectively, and similar reactions were carri out with dioxolane and a, 3-usaturated nitropyranones [127]. 

Abstract This review covers recent advances in the field of radical chemistry on solid phase. Intermolecular processes using both immobilized radicals with solution-phase acceptors and immobilized acceptors with radicals in solution are discussed, as are radical cyclization reactions on polymer supports. Progress in the development of solid-phase asymmetric radical processes and the design of linkers cleaved by radical processes are also discussed. 

Enholm [26] has reported the first examples of asymmetric radical cy-clizations on soluble polymer supports. The stereocontrol element employed consists of a (+)-isosorbide group attached by a 4-carbon chain to each subunit of a soluble succinimide-derived ROMP backbone. Treatment of the radical cychzation substrate 162 with tributyltin hydride in the presence of zinc chloride followed by hydrolysis of the resulting polymer-supported ester 163 gave the desired product 164 in 80% yield and > 90% ee (Scheme 38). The use of alternative Lewis acids, such as magnesium bromide etherate and ytterbiiun (III) triflate, resulted in lower enantioselectivities, 84% and 72% respectively. No such decrease in selectivity was observed in analogous reactions carried out off-support [27], suggesting that the polymer backbone is somehow responsible for this phenomenon. 

Asymmetric Radical Reactions. Several reports have documented the utility of nonracemic fra/w-2,5-dimethylpyrrolidine as a chiral auxiliary in asymmetric radical reactions. For example, the addition of -hexyl, cyclohexyl, and f-butyl radicals to the chiral acrylamide of 4-oxopentenoic acid provided four diastere-omeric products resulting from a- and p-addition (eq 7). The isomers resulting from p-addition were formed with no diastereoselectivity however, the isomers resulting from a-addidon were formed in ratios of 16 1,24 1, and 49 1. Unfortunately, the application of this chemistry is limited due to the poor regioselectivity in the addition and difficulty in removal of the chiral auxiliary. 

The first catalytic asymmetric radical-mediated allylation was reported in late 1997 by Hoshino and coworkers, who studied the allylation of an a-iodolac-tone substrate, Eq. (19) using trimethylaluminum as Lewis acid and a silylated binaphthol as the chiral catalyst, with triethylborane as radical initiator [62]. Use of one equiv. of diethyl ether was crucial for high enantioselectivity, providing an ee up to 91% in the presence of one equiv. of catalyst, with only a 27% ee in the absence of ether, and poorer ee s when other ethers were employed. In the catalytic version, the ee s dropped off vs. the stoichiometric reaction, with an ee of 81% with 0.5 equiv., and 80% with 0.2 equiv., and 72% with 0.1% catalyst. As in the above example, the presumed chiral intermediate involves complexation of the lactone radical with the Lewis acid-binaphthol complex, with the diethyl ether perhaps as a ligand on the aluminum. 

The N-Trifluoromethanesulfonyl group increases Lewis acidity of (S,S) diazaaluminolidine (85a), which associates with 3-acryloyl-l,3-oxazolidine-2-one conformationally tightly so as to control the preferred one-side access of the diene in the transition state 86 of the reaction of 87 with 88, as shown in Scheme 5.23 [8]. The same catalysts (85a-c) have been employed for asymmetric radical allylation on the quaternary carbon of coumarin derivatives [9]. Highly trifluoromethylated diols (90 and 91) have... 

A decade ago, radical reactions were thought to be of little use in synthesis due to lack of selectivity. Much progress has recently been made in this domain, and it has even become possible to control the stereoselectivity in many radical reactions [1469]. Curran, Giese, Porter and their coworkers initiated the study of asymmetric radical addition reactions by introducing chiral residues either on the radical precursor or on the alkene. 

Another application of asymmetric radical additions, proposed by Giese, Porter and coworkers [276, 334, 1475], is the addition of c-CgHji or ferf-Bu radicals to chiral acrylamides 7.124 (R = H) and 7.125 (R = H) followed by trapping of the initial radical adduct by an acceptor such as a thiopyridone or allyltribu-tylstannane. These reactions are carried out between -35 and + 80°C, and they are highly diastereoselective (Figure 7.78). The adduct radicals are trapped on the least hindered face of the conformation in which A(l,3) strain and dipolar interactions are minimized [454],... 

The photolysis of an optically active acetyl silane 1 (eq. [1]) implies the formation of an asymmetric radical 2 which retained its configuration upon trapping by carbon tetrachloride (17). The chlorosilane 3 was then reduced to the hydrosilane 4 with inversion of configuration. 

Chiral auxiliary for asymmetric radical addition and allylation. Curran, Re-bek et al.1 have prepared the chiral auxiliary 2 from 1 by manipulation of the carboxylic acid groups to provide ( )-2, enr/o-7-(2-benzoxazolyl)-l,5,7-trimethyl-3-azabicyclo[3.3.1]nonan-2-one. The racemic auxiliary is then resolved via its menthyl carbamate to provide both (R)- or (S)-2. 

One important application of Lewis acid to asymmetric radical reactions is in the control of tacticity in free radical polymerizations. Recently, Porter [38] showed that Sc(OTf)3 modulates the polymerization of oxazolidinone acrylamides to produce highly isotactic copolymers (Scheme 12). The same study described homopolymerizations in which the m/r dyad ratio was dependent on the reaction temperature. 

The second key step is lactone formation from the carboethoxy substituted cyclohexanone unit in 44. The third key step is construction of the tricyclic ring system by asymmetric radical cyclization of 43, and construction of 43 from 2-isopropylphenol (42) using alcohol chiral auxiliaries (R OH) was designated as the fourth key step. This disconnection scheme represents Yang s specific approach using key chemical transformations such as radical cyclization (see sec. 13.7). Clearly, other disconnections are possible, and at each stage other disconnections could lead to alternate synthetic trees. 

Scheme 39. Asymmetric radical coupling reaction with molybdenum boroxycarbenes.

Scheme 2.20 Organocatalytic asymmetric radical-mediated polyene cyclization reactions reported by MacMillan.

DBPAMA) ([a]365+74° using (+)-NMT [a]36s -53° using (-)-NMT) was obtained. The specific rotation values suggest that the helical-sense excess (ee) may be -30-40%. In contrast to the asymmetric radical polymerization of PDBSMA, the optically active product was completely soluble in this case. 

This topic has been reviewed by Malacria, Pelhssier, and their coworkers [5] in two excellent articles. The present section deals with asymmetric radical domino processes covering chiral auxihary-directed and chiral catalyst-driven processes mainly developed in the past several years. However, chiral reagentradical domino reactions have rarely been reported. 

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