Synthesis radical additions

The recognition of the usefulness of radical reactions as a synthetic tool has prompted the exploration of this method for branched-chain sugars synthesis. Radical addition to an olefin is one of the most popular reactions yet investigated [10], Two approaches have been devised an intramolecular version, which is mostly a 5-exo cyclization and an inter-molecular version in which the radical is trapped by an activated olefin. 

This synthesis is only one example of a wide range of reactions which involve aryl (or alkyl) radical addition to electron-deficient double bonds resulting in reduction.The corresponding oxidative reaction using aryl radicals is the well known Meerwein reaction, which uses copper(II) salts. 

A radical approach to asymmetnc iildol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a tutroalkene, has been reported, as shown in Eq 4 93 The radical precursor is prepared from the corresponding carboxyhc acid by the Barton reaction, which has been used for synthesis of new fi-lactams ... 

Scheme 13. Intramolecular radical addition/fragmentation in Boger s synthesis of (+)-CC-1065.

Scheme 17. Danishefsky s radical addition/fragmentation process in a synthesis of (+)-3-demethoxyery-thratidinone [( )-93].

A radical carboxyarylation approach was introduced as the key step in the total synthesis of several biologically important natural products (Scheme 27). Treatment of thiocarbonate derivatives 112 (R = Me or TBS) with 1.1 equiv of (TMS)3SiH in refluxing benzene and in the presence of AIBN (0.4 equiv added over 6h) as radical initiator, produced compound 113 in 44% yield. This remarkable transformation resulted from a radical cascade, involving (TMSlsSi radical addition to a thiocarbonyl function (112 114), 5-era cyclization (114->115) and intramolecular 1,5-ipso substitution (115 116) with the final ejection of (TMSlsSiS radical. 

There are several procedures for synthesis of terminal alkenyl stannanes that involve addition to aldehydes. A well-established three-step sequence culminates in a radical addition to a terminal alkyne.150... 

Radical reactions used in synthesis include additions to double bonds, ring closure, and atom transfer reactions. Several sequences of tandem reactions have been developed that can close a series of rings, followed by introduction of a substituent. Allylic stannanes are prominent in reactions of this type. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The radical addition to a ketone has been used as a key step in the preparation of (E)-endo-begamoten-12-oic acids [115] and for the synthesis of carbacephams [118,119]. 

Dubois et al. [184] reported the synthesis of phosphorus based dendrimers terminated with multivalent palladium complexes. Iterative free radical addition... 

Scheme 3.34. Intermolecular domino radical addition procedure for the synthesis of silyl-protected allylic alcohols.

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

Carbon-carbon bond formation is a fundamental reaction in organic synthesis [1, 2,3,4], One way to form such a bond and, thus, extend a carbon chain is by the addition of a polyhalogenated alkane to an alkene to form a 1 1 adduct, as shown in Scheme 1. This reaction was first reported in the 1940s and today is known as the Kharasch addition or atom transfer radical addition (ATRA) [5,6], Historically, Kharasch addition reactions were conducted in the presence of radical initiators or... 

Dilworth, J.R., Griffiths, D.V., Hughes, J.M., and Morton, S., Synthesis of 2-S-(2-tetrahydropyranyl)thioethylphosphines and 2-mercaptoethylphosphines by free radical addition of phosphines to 2-(vinylthio)tetrahydropyran, Phos-ph Sulf, Silic. Relat. Elem., 71, 249, 1992. 

This reaction is very important for the synthesis of natural products and for the design of diversely substituted ligands. The use of Sml2 in radical additions of nitrones to 0.,j3-unsaturated amides and esters, constitutes a convenient synthesis of various functionalized y-amino acids with high enantiomeric excess (Schemes 2.114 and 2.115) (531-533). 

Michael-type radical cyclization." A short synthesis of 3-demethoxyerythra-tidinone (3) involves a Michael-type radical addition. Thus 1 on reaction with BujSnH (AIBN) affords 2 as a single isomer in 65% yield. This product is converted by a three-step sequence into 3. 

A modified version of the Brown-Negishi reaction using B-alkylcatechol-boranes was reported (Scheme 32). This novel method is based on a simple one-pot procedure involving the hydroboration of various substituted alkenes with catecholborane, followed by treatment with catalytic amount of oxygen/DMPU/water and a radical trap. Efficient radical additions to a,ft-unsaturated ketones and aldehydes have been reported. Primary alkyl radicals are efficiently generated by this procedure and the reaction has been applied to a 300 mmol scale synthesis of the y-side chain of (-)-perturasinic... 

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... 

Scheme 37 Application of enantioselective conjugate radical addition total synthesis of Ricciocarpin A and B...

Curran DP (1991) Radical Addition Reactions. In Trost BM, Fleming I, Semmelheck MF (eds) Comprehensive Organic Synthesis. Pergamon, Oxford, p 715-777... 

In view of this background, it is the aim of this chapter to organize the fundamentals of radical additions to 1,2-dienes and to present its state of the art in organic synthesis. All aspects of enyne allene cyclizations [19, 20] have been omitted since this topic is addressed in Chapter 20. In order to simplify the mechanistic discussion, the positions and Jt-bonds of allenes have been consistently numbered using the nomenclature outlined in Figure 11.1. 

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