Asymmetric radical additions

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]. 

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],... 

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. 

Scheme 5.52 Menthol-controlled asymmetric radical addition/cyclization reaction.

Scheme 19.63 Asymmetric radical addition catalysed by Al-BINOL.

The asymmetric radical addition of a-methylenebutyrolactone and Bui was reported by the Sato group in 1995 using (I )-BINOL-Al(iii) as the catalyst (Scheme 19.63). Although a low enantioselectivity was obtained, this is the first example of asymmetric radical reaction controlled by a chiral Lewis-acid catalyst. 

Bimetallic mthenium complexes with a chiral ligand (Ru-67) have been known to induce asymmetric radical addition reactions by enantiomeric selectivity during retrieving process of the halogen from the oxidized metal catalyst. 

Aluminum Lewis acid was also used in asymmetric radical addition of nucleophilic radical including alkyl radical to a,p-unsaturated carbonyls. Yonemitsu and CO workers reported diastereoselective radical cyclizationof alkynylacrylate equipped with 8-phenylmenthyl chiral auxiliary (Scheme 6.171) [201]. 

As the first example of asymmetric radical addition using chiral aluminum Lewis acid, in 1995, Urabe and Sato reported enantioselective inter molecular radical addition of butyl radical generated from iodobutane to exo-methylene lactone (Scheme 6.172) [202]. In this reaction, chiral Lewis acid (i )-(14) derived from (R)-BINOL and Et2AlCl gave only low enantioselectivity (up to 23% ee). Shortly after this report, Nishida and coworkers reported that in the presence... 

Stoffelbach F, Richard P, Poli R, Jenny T, Savary C. Half-sandwich Mo(III) complexes with asymmetric diazadiene ligands. Inorg Chim Acta. 2006 359 4447-4453. lizuka Y, Li ZM, Satoh K, et al. Chiral (-)-DIOP ruthenium complexes for asymmetric radical addition and living radical polymerization reactions. Eur J Org Chem. 

Toru T, Watanabe Y, Tsusaka M, Ueno Y. High 3-stereoselectivity in asymmetric radical-addition to a-sulfinylcyclopentenones. J Am Chem Soc. 1993 115 10464— 10465. 

Isoprene can be polymerized using free radical initiators, but a random polymer is obtained. As with butadiene, polymerization of isoprene can produce a mixture of isomers. However, because the isoprene molecule is asymmetrical, the addition can occur in 1,2-, 1,4- and 3,4- positions. Six tactic forms are possible from both 1,2- and 3,4- addition and two geometrical isomers from 1,4- addition (cis and trans) ... 

A similar but asymmetric variant of the reaction, involving the radical addition of alkyl iodides and trialkylboranes to chiral azirine esters derived from 8-phenyl-menthol and camphorsultam, in the presence of a Cu(i) catalyst, has subsequently been reported [64]. The diastereoselectivity of the addition is variable (0-92% de)... 

The first five telomers (n = 1 - 5) were isolated and identificated. The authors showed that telomers T2 and T3 are preferentially formed in one stereoisomeric form (with minor amounts of other possible isomers), i.e. the radical addition reaction makes it possible to perform asymmetric control at the steps of chain transfer and chain growth. The partial chain transfer constants Cn are given in this work, which are within the range from 0.3 to 0.5 for radicals C2-C5. We consider... 

Scheme 3.37. Domino radical addition/cyclization-reaction for the asymmetric synthesis of (3-aminobutyrolactones.

A radical approach to asymmetric aldol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a nitroalkene, has been reported, as shown in Eq. 4.93.113 The radical precursor is prepared from the corresponding carboxylic add by the Barton reaction,114 which has been used for synthesis of new (3-lactams.115... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

A recent application of enantioselective conjugate radical additions was seen in the synthesis of (+)-ricciocarpins A and B [95]. The key step in the synthesis was an asymmetric addition of a functionalized radical precursor 141 to afford intermediate 142 (Scheme 37). A chiral catalyst screening revealed that Mgt and bisoxazoline ligand 19 was optimal for achieving... 

CH2CI2, —78 °C (61) Catalyst for asymmetric 167 conjugate radical addition... 

D.4. CATALYTIC ASYMMETRIC MICHAEL ADDITION OF ALKYL RADICALS 587... 

TABLE 8D.5. Catalytic Asymmetric Michael Addition of Propyl Radical to A -Cinnamoyloxazolidinone... 

The combination of Baylis-Hillman reaction and tandem radical addition/ cyclization sequences [259], has been reported as a useful synthetic tool for the asymmetric synthesis of functionalized monocyclic and bicyclic (3-lactams (III and IV, Fig. 7). 

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