Absolute stereochemistry radical

The absolute stereochemistry at the sulfoxide sulfur atom in some /J-phenylsulfinyl radicals (prepared in situ by treating 2-bromo-3-phenylsulfinylbutanes with tributylstan-nane) controls the stereochemistry (i.e., cis vs. trans) of the olefinic products which are formed104. Implicit in this result is that loss of the sulfinyl group occurs more rapidly than rotation about C-2-C-3 of the intermediate radical105. 

The absolute stereochemistry of the products formed from radical addition onto 2-propenyl sulfone and 1-phenylethenyl sulfone were found to be opposite. The reactions proceed through a five-membered transition state... 

The absolute stereochemistry for 150 (entries 2 and 3) was determined by hydrolysis and conversion to known compounds. Assuming a tetrahedral or cis octahedral geometry for the magnesium [110], the product stereochemistry is consistent with si face radical addition to an s-cis conformer of the substrate. This is the same sense of selectivity as that obtained with oxazo-lidinone crotonates or cinnamates suggesting that the rotamer geometry of the differentially substituted enoates is the same. The need for stoichiometric amount of the chiral Lewis acid to obtain high selectivity with 148 in contrast to successful catalytic reactions with crotonates is most likely a reflection of the additional donor atom present in the substrate. 

The Diels-Alder reaction is one of the most powerful and efficient processes for formation of six-membered rings with the potential of controlling the relative and absolute stereochemistry at four newly created stereogenic centers [1]. Relative stereochemistry is usually well-defined because of the formation of a cyclic transition state arising from suprafacial-suprafacial interaction, with endo approach [2]. The reaction can be accelerated by Lewis acids, high pressure, or radical cations. Diels-Alder reactions catalyzed by Lewis acids are generally more regio- and stereoselective than their thermal counterparts [3]. 

Homolytic fission of the chiral ammonium ylide (143) generates two diastereomeric radical pairs which evolve by two different routes (a) cage recombination leads to the two diastereomeric ketoamines (161) and (162), where the migrating center has retained its absolute stereochemistry (b) radical escape gives achiral free radicals that combine to yield racemic products (Scheme 35). 

Lipoxygenase enzymes are known to oxidize arachidonic acid at six possible positions. The chemical requirement for this oxidation (Eq. 4.1) appears simply to be a skipped cis diene which can produce (via the enzyme) a stabilized allylic radical, which then traps molecular oxygen to form a conjugated cis-trans diene hydroperoxide. Chart 4.1 shows the six possible mono-oxidation products as members of the HETE family. All of these compounds have been shown to be natural products. Only in the cases of 8 and 9 HETEs is the absolute stereochemistry not definitively known. Nevertheless, it is speculated that 8-HETE has the alcohol in the (5)-configuration and 9-HETE is of the (R) absolute... 

Dussault has reported a remarkable example of stereocontrolled peroxyl radical rearrangement (cf. 35 36) in the context of his asymmetric total synthesis of the marine natural product plakortin and its C6-epimer, c t-chondrillin (Scheme 50) [89]. A systematic study of initiators and reaction conditions revealed that the yield of rearranged products can be substantially improved by using DTBN in conjunction with an excess of TBHP [89]. Equilibration of 35 under these conditions provided a 1 1.2 mixture of 35 and 36, which were obtained as single diastereoisomers after separation on silica gel in yields of 29 and 36%, respectively. The synthesis of c t-chondrillin allowed the assignment of absolute stereochemistry to the natural product chondrillin [89]. 

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). 

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

This section provides the rationale for the selection of the chiral cyclopropyl and vinyl systems in the investigation of the mechanism of organometallic compound formation. The absolute configurations and optical purities of these systems have been established. The ability of these systems to perform as effective probes in such mechanistic studies resides in the knowledge of the stereochemistry of their radical and carbanion intermediates. Do the radical and carbanion intermediates retain or lose their configurations ... 

The radical mechanism is further supported by several other results in which stereochemical scrambling and isotope scrambling are observed in the sMMO-catalyzed hydroxylation of hydrocarbons. Retention of stereochemistry is a valid measure of the concertedness of a reaction only if it can be assumed that the retention is not due to constrains imposed by the active site geometry of the enzyme. Loss of stereochemistry is absolutely indicative of a reaction requiring an intermediate and thus implies a nonconcerted reaction [2]. Scrambling of stereochemistry was observed with hydroxylation of c/5-l,4-dimethylcyclohexane and c/ -l,3-dimethylcyclohexane with sMMO system from Af. capsulatus (Bath) as shown in eqs. (7) and (8) [75]. This type of stereochemical scrambling was also observed in the hydroxylation of norbornane by rabbit liver microsomes and in the oxidation of camphor by cytochrome P-450 [2]. 

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