Electrophilic addition chemoselectivity

The concept of armed/disarmed glycosyl donors was subsequently extended by other groups to thioglycosides21 and selenoglycosides.64 A similar strategy has been used by Friesen and Danishefsky to achieve chemoselectivity in electrophilic addition to glycal double bonds.65... 

Fig. 5.4. Enthalpy profile for the electrophilic addition of Br2 (reactions proceeding towards the left) and for the electrophilic substitution by Br2 (reactions proceeding towards the right) of cyclohexene (top) and of benzene (bottom). Altogether, the facts presented here are likely to be prototypical of the chemoselectivity of all electrophilic reactions on alkenes versus benzenoid aromatic compounds. In detail, though, this need not be true both in the alkene and the aromatic compound AWSubstitution as well as AWadditio depend on the electrophile, which is why an electrophilic dependency can in principle also be expected for AAH = AWsubstitution - A//a(1(l t. ol. ...

Ally lie sulfides react with DMTSF chemoselectively at the sulfur atom, generating thiosulfonium ions. This ion formation is reversible and the allylic thiosulfonium ion is capable of a [2,3]-sigmatropic rearrangement before subsequent electrophilic addition to the alkene. ... 

With this mechanistic scheme, the chemoselectivity of the addition and the formation of rearranged chlorides (but not acetates) have been chosen as criteria to differentiate the ion pair mechanism from the purely ionic one and, on the basis of both criteria, the authors suggest the involvement of a tight ion pair for the addition of ArSCl in AcOH to diene 62 and of solvent separated ion pairs to triene 108. The effects related to the presence of added electrolytes, which favor the formation of rearranged acetates, have been considered in this work127 as evidence that even a larger separation of ions, which should lead to more electrophilic species, is possible. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

Compared with aldehydes, ketones and esters are less reactive electrophiles in the addition of dialkylzincs. This makes it possible to perform a unique reaction that cannot be done with alkyllithium or Grignard reagents, which are too reactive nucleophiles. For example, Watanabe and Soai reported enantio- and chemoselective addition of dialkylzincs to ketoaldehydes and formylesters using chiral catalysts, affording enantiomerically enriched hydroxyketones 30 (equation 12)43 and hydroxyesters 31 in 91-96% , respectively (equation 13). The latter are readily transformed into chiral lactones 3244. 

The addition of carbonylated electrophiles to the 2-lithio derivative of 4-oxazolinyloxazole 132 allowed the efficient preparation of 5-phenyloxazoles 134 bearing a variety of hydroxyalkyl groups at C-2 position and a carboxyl (or formyl) function at C-4. This protocol suppresses the troublesome electrocyclic ring-opening reaction and allows access to the target compounds by simple chemical transformation of the oxazoline moiety of 133 <02JOC3601>. A direct chemoselective C-2 silylation of oxazoles was performed by treatment of the lithiated parent compounds with silyl triflates <02TL935>. 

The apparent chemoselectivity for the addition of the electrophilic S-centered radicals to the less electron-rich alkyne moiety in enyne 138 can be rationalized by the fact that addition of S radicals to both aUcenes and alkynes proceeds smoothly (the rate constants for addition of S radicals to alkenes are about three orders of magnitude larger than those for the addition to alkynes), but is also reversible. However, the reversibility is less pronounced for the radical addition to alkynes, due to the high reactivity of the vinyl radicals formed (compared to alkyl radicals), which undergo subsequent reactions at faster rates than undergoing fragmentation back to the S... 

The intramolecular conjugate addition of in situ, chemoselectively generated amines 2 bearing an electrophilic double bond in the cu-position leads to functionalized pyrrolidines and piperidines 3 under very mild conditions34. The cyclization step occurs smoothly and the piperidine and pyrrolidine derivatives are obtained as a mixture of diastereomers with good diastereose-lection in most cases. The reactions are under kinetic control and the geometry of the starting alkene does not seem to have an influence on the stereochemical outcome of the cyclization step. 

Chemoselectivity is affected by electronic factors as well. Cross experiments show that small changes in the electrophilic nature of the carbonyl group are responsible for marked differences in the nucleophilic reactivity of Ti and Zr reagents (equations 22 and 23). The electronic nature of the nucleophilic moiety of the metal reagent also affects the chemoselectivity of the nucleophilic addition. This is the case for some special titanium(IV) triisopropoxide derivatives [e.g. (53)-<56)] which are selective towards aldehydes and give high addition yields, due to their resonance-stabilized residues acting as nucleophiles. ... 

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