Regioselective functionalization

The new family of phospholes with 2,4,6-trialkylphenyl substituent on the phosphorus atom show, in many respects, a special reactivity. Due to the flattening of the P-pyramid, the arylphospholes exhibit aromaticity and hence underwent Friedel-Crafts reactions. The regioselective functionalization through reaction with phosphorus tribromide gave a variety of phospholes with an exocyclic P-moiety. Novel phosphole platinum and rhodium complexes were prepared and a part of them was tested in hydroformylation reactions. 

The key precept for any strategy would involve complete stereochemical control and precision in the degree of sulfidation. Accordingly, we envisioned that the epipolysulfides could arise from the ionization of a C15 hemiaminal derivative and subsequent cyclization of a polysulfane onto the resultant /V-acyliminium ion. The polysulfane would be derived from the corresponding thiol accessed by regioselective functionalization of the Ca(Trp) position. 

Alkyl groups of compounds other than alkanes can be regioselectively functionalized using C-H activation chemistry. For example, acyclic and cyclic ethers can be activated by Ir(m) complexes to yield carbene complexes (Equation (25)).35... 

The total synthesis of ( )-yohimbine via regioselective functionalization of 18,19-dehydroyohimbinone (434) has been reported by Ninomiya et al. (231). Key intermediate 434 was prepared by enamide photocyclization of 432, fol-... 

KOBu-f in hexane gives a precipitate of butylpotassium" " , the reactivity of a slurry of BuLi—KOBu-f does not match that of BuK. Simplistically, superbases can be considered to be organolithiums solvated by very electron-donating ligands (much more so than THF or TMEDA). As synthetic tools they provide a useful top end to the armoury of bases for regioselective functionalization by deprotonation. 

Stereoselective alkylation with aliphatic bromides and iodides of the Schiff bases of tert-butyl glycinate with (—)-(15,25,55)-2-hydroxypinan-3-one or (+)-(lR,2R,5R)-2-hydroxy-pinan-3-one 150 was reported to produce lipidated amino acids as d- and L-enantiomers in 80 to over 90% ee. 151 Similarly, the asymmetric synthesis of a derivative of arachidonic acid (4) has also been reported. The pure enantiomer was obtained via regioselective functionalization of a chirally pure glutamic acid. 152 ... 

An interesting series of transformations have been reported which demonstrate a variety of selecti-vities of organopalladium chemistry. 1,3-Dienes can be regioselectively functionalized in a 1,4-fashion... 

Intramolecular hydrosilylation of oj-dimethylsiloxyalkynes such as 114, readily derived from alkynol 113, provides a convenient method for the regioselective functionalization of internal alkynes in combination with the Tamao oxidation and other transformations. An example of such a process giving 117 via 115 and 116 is illustrated in Scheme 1487. 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

Breslow s template-directed remote oxidation of steroids utilizes an aryl iodide as a template to direct the oxidation of steroid tertiary carbons by the radical relay mechanism, in which a chlorine radical is transferred from a [9-1-2] [PhICl] radical to the iodine atom of the template and then relayed to a geometrically accessible hydrogen atom. This method allows a highly regioselective functionalization of nonactivated carbon atoms of steroids [Eq. (78)] [137,138]. 

Besides the 1,3-dipolar cycloaddition of azomethine ylides to C60, the Bingel cycloprop anation reaction is widely used for regioselective functionalization of fullerenes. In principle, this versatile modification involves the generation of carbon nucleophiles from a-halo esters and their subsequent addition to C60 [19]. The addition takes place exclusively on double bonds between two six-membered rings of the fullerene skeleton, yielding methanofullerenes. As shown in Scheme 2, addition of diethylbromomalonate to C60, in the presence of an auxiliary base... 

Cyclodextrins, described in Chapter 1, are naturally occurring macrocycles that exist in a number of different sizes. Externally they are decorated with hydroxyl groups but have hydrophobic central cavities that can bind appropriately sized guests. In fact they appear to be ideal molecules to use as a basis for an enzyme mimic. Furthermore the hydroxyl groups can be regioselectively functionalized. 

Again, benzyne derivatives could be considered as reactive alkynes and we have studied the anionic cyclization reactions of functionalized vinyl- and aryllithiums to these intermediates. We have developed a useful methodology that gives rise to a wide range of regioselectively functionalized heterocycles161. For instance, 4-functionalized indoles 379 have been prepared from simple A-2-bromoallyl-2-fluoroanilines 378. Treatment of these... 

The regioselective functionalization of A -pyirolines at the 2-position by metalatitm of the derived r-butylfomuunidine (21) is shown in Scheme 27." Metalation at the 2-position of a pyirole having an ortho director at the 3-position is readily achieved. Functionalization of a pyrrole at the 3-position by ortho metalation of a 2-substituted derivative is more problematic, with a mixture of 3- and 5-substituted... 

It is possible to achieve some selectivity using this method. As illustrated above, tertiary C—H sites are much more reactive than primary C—H sites. Radical-stabilizing functional groups also impart selectivity, as illustrated by the regioselective functionalization of (9 equation 4). ... 

Efficient procedures for the regioselective functionalization of calix[5]arenes are scarce. Only recently was the 1,2,4-triester obtained in 49% by reaction of 2b with camphor-sulphonyl chloride . (For crown ethers see Section IV.D.)... 

Allylic and dienyl sulfones have been prepared by conjugate addition to 1,3-dienes ". Phenylsulfonyhnercuration of conjugated dienes gives mercury adducts which can be treated with base to afford phenylsulfonyldienes. 2-(Phenylsulfonyl)-l,3-dienes can be stereo- and regioselectively functionalized via Michael addition of nucleophiles to give allylic sulfones. A key intermediate in the synthesis of a Monarch butterfly pheromone 4 was prepared by BackvaU and Juntunen by alkylation and subsequent palladium-catalyzed substitution of the allylic sulfone formed by Michael addition of dimethyl malonate to 2-(phenylsulfonyl)-l,3-butadiene (equation 10). 

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