Radical reactions stereoselectivity

Most radicals located on saturated bonds are jt-radicals with a planar configuration and may be depicted with the free spin located in a p-orbital (1). Because such radical centers are achiral, stereochemical integrity is lost during radical formation, A new configuration will be assumed (or a previous configuration resumed) only upon reaction. Stereoselectivity in radical reactions is therefore dependent on the environment and on remote substituents. 

Synthetic strategies based on multistep radical reactions have steadily grown in popularity with time. The knowledge of radical reactivity has increased to such a level as to aid in making the necessary predictions for performing sequential transformations.Silanes, and in particular (TMSlsSiH, as mediators have contributed substantially in this area, with interesting results in terms of reactivity and stereoselectivity. ... 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

Stereospecificity of this reaction reaches 15 1 for telomer T3. Telomer T3 is a crystalline product, this allowed the authors to use X-ray diffraction analysis for studying stereochemistry. Stereoselectivity observed in the formation of T3 shows that both addition step and the step of halogen transfer to the growing radical proceed stereoselectively in this case. 

Thus, this first example of stereoselective radical reaction, initiated with the system based on Fe(CO)5, shows opportunities and prospects of using the metal complex initiators for obtaining the stereomerically pure adducts of bromine-containing compounds to vinyl monomers with chiral substituents. 

A stereoselective radical reaction of the ester of M-hydroxy-2-pyridinethione (see also Sect. 4.1) to chiral vinylphosphine oxides has also been described and moderate to good diastereomeric ratios have been obtained for the compound 112 [70] (Scheme 33). 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

Attainment of higher chemoselectivity (cross-coupling) and stereoselectivity in both radical reactions is expected to be one of the coming goals in this field. 

Optically active iV-unprotected-2-pyrrolidinones 194 were obtained from selenocarboxylate or allylamine via radical cyclization and subsequent one-step cleavage of the C-O and C-N bond of the inseparable mixture of the two bicyclic oxyoxazolidinones 192 and 193 with -Bu4NF. The initial radical reaction is highly stereoselective. Products were obtained with ee up to 90%. The mandelic acid 195, which served as the chiral auxiliary in this method, was recovered with no loss of optical activity (Equation 33) <2003T6291>. 

Anomeric halides follow the typical reactivity order F < Cl < Br < I for nucleophilic substitutions. They have been used in stereoselective O-glycosylation, nucleophilic displacement, and carbanion as well as in radical reactions. 

Triethylborane in the presence of very small amounts of oxygen is an excellent initiator for radical chain reactions. For a long time it has been known that trialkylboranes R3B react spontaneously with molecular oxygen to give alkyl radicals (Reaction 4.7), but only recently has this approach successfully been applied as the initiation [22]. The reactions can be run at temperatures as low as — 78 °C, which allow for a better control of stereoselectivity (see below). 

The general concepts of stereoselectivity in radical reactions have been illustrated in a number of recent books. Readers are referred to those books for a thorough treatment [1,2]. The following sections deal with a collection of applications where silanes act as mediators for smooth and selective radical strategies, based on consecutive reactions. 

Stereoelectronic effects can be invoked for the radical reaction at anomeric centre of carbohydrates. The high stereoselective preparation of a-substituted C-glycosyl phosphonates in a a p ratio of 98 2 was achieved by reductive addition of bromide 2 to a-phosphonoacrylate (Reaction 7.5) [10]. Yields (in parentheses) depend on the sugar configuration D-galacto (80%), D-manno (47 %), D-gluco (30 %) and L-fuco (62 %). 

Only a few radical reactions have been applied to the functionalization of 1,3-dioxanes or 1,3-dithianes bearing one exo- or mdo-Ao ih c bond. In all cases, ring formation was the goal. The common reagent system, BusSnH/AIBN, was used to achieve a stereoselective ring closing hydrostannylation of an alkenyl alkyne subunit (AIBN = 2,2 -azobisiso-butyronitrile Equation 36) <1998JOC9626>. 

In addition to allylsilanes, CM can also be applied to allylstannanes, which serve as valuable reagents for nucleophilic additions and radical reactions.To date, only eatalyst 1 has been shown to demonstrate CM reactivity in the preparation of 1,2-disubstituted allylstannanes, as ruthenium catalysts were found to be inactive in the presence of this substrate class.Poor stereoselectivities were generally observed, with the exeeption of one instance of >20 1 Z-selectivity in the reaction of allyltributylstannane with an acetyl-protected allyl gluco-side. 

B. Giese, The stereoselectivity of intramolecular free radical reactions, Angew. Chem. Int. Ed. Engl. 28 969 (1989). 

B. Giese and T. Witzel, Stereoselective radical reactions with enolones, Tetrahedron Lett. 28 2571 (1987). 

Photoinitiation of free-radical reactions.2 Use of thermal initiators for radical sources, such as AIBN or dibenzoyl peroxide, requires temperatures >50°. This perester, in contrast, decomposes at room temperature or below on irradiation at 360 nm. This mode of initiation can be useful when stereoselectivity is enhanced at lower temperatures. 

The radical mechanism has also been proposed as a general mechanism for oxidation of alkenes and aromatics, but several objections have been raised because of the absence of products typically associated with radical reactions. In classical radical reactions, alkenes should react also at the allylic position and give rise to allyl-substituted products, not exclusively epoxides methyl-substituted aromatics should react at the benzylic position. The products expected from such reactions are absent. Another argument was made against the radical mechanism based on the stereoselectivity of epoxidation. Radical intermediates are free to rotate around the C C bond, with the consequence that both cis- and /rani-epoxides are formed from a single alkene isomer, contrary to the evidence obtained with titanium silicates (Clerici et al., 1993). 

This section presents some general chemoselectivity considerations for designing substrates and planning experimental conditions for radical reactions. More detailed concerns of chemo-, regio- and stereoselectivity are addressed for each specific technique in the individual sections below. 

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