Arylations and a-Alkylations

The catalytic enantioselective direct alkylation reaction of enolates is a less developed field. Early research from Evans group demonstrated that preformed titanium enolates derived from chiral Af-acyloxazolidinones reacted with orthoesters to provide the alkylated adducts with high levels of diastereo-control. In2005, the same group reported the enantioselective nickel-catalysed 

Shibata, T. Horikawa, S. Suzuki, S. Nakamura, T. Toru and M. Shiro, Chem.-AsianJ., 2009, 4,1411-1415. 

Williams, Synthesis of Optically Active a-Amino Acids, Pergamon, Oxford, 1989 (b) R. O. Duthaler, Tetrahedron, 1994, 50, 1539-1650  

Comelles, A. Pericas, M. Moreno-Manas, A. Vallribera, G. Drudis-Sole, A. Lledos, T. Parella, A. Roglans, S. Garcia-Granda and L. Roces-Fernan-dez,/ Org. Chem., 2007, 72, 2077-2087. 

Kanger and T. Pehk, Tetrahedron Lett, 1997, 38, 5051-5054. 

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X-ray analysis of an optically active oxaziridine substituted at nitrogen with the 1-phenylethyl group of known configuration led to the absolute configuration (+)-(2R,3R)-2-(5-l-phenylethyl)-3-(p-bromophenyl)oxaziridine of the dextrorotatory compound as expected, C-aryl and A-alkyl groups were trans to each other (79MI50800). 

The versatility of 5-nitrosopyrimidines in pteridine syntheses was noticed by Pachter (64MI21603) during modification of the Timmis condensation between (262) and benzyl methyl ketone simple condensation leads to 4-amino-7-methyl-2,6-diphenylpteridine (264) but in the presence of cyanide ion 4,7-diamino-2,6-diphenylpteridine (265) is formed (equation 90). The mechanism of this reaction is still uncertain (63JOC1187) it may involve an oxidation of an intermediate hydroxylamine derivative, nitrone formation similar to the Krohnke reaction, or nucleophilic addition of the cyanide ion to the Schiff s base function (266) followed by cyclization to a 7-amino-5,6-dihydropteridine derivative (267), oxidation to a quinonoid-type product (268) and loss of the acyl group (equation 91). Extension of these principles to a-aryl- and a-alkyl-acetoacetonitriles omits the oxidation step and gives higher yields, and forms 6-alkyl-7-aminopteridines, which cannot be obtained directly from simple aliphatic ketones. 

Thy hydrolyzable ether units in the lignin are P-aryl, a-aryl, and a-alkyl ether linkages. 

By using catalyst Ir-41, Han etal. [50] hydrogenated A -aryl and A -alkyl ketimines with good to excellent enantioselectivities (up to 98% ee) under mild reaction conditions (Scheme 25). 

Zinc enolates of (V -bissilylglycine esters, according to van Koten and coworkers, condense with N-silylimines with high anti selectivity (Table 20 entries 18-20). °° These results parallel those previously described in Section 4.1.3.2.2.i using N-ary - and A/-alkyl-imines and are consistent with a C(Z,E)t transition state. Reactions of N-silylimines are slightly less anti selective, however, than those of N-aryl- and A/-alkyl-imines. Retroaldolization prior to cyclization has been cited as a possible cause for the erosion in stereoselectivity based on the slow rates of cyclization found in the reactions of entries 19 and 20. 

An umpolung reaction at the a-carbon of carbonyl compounds has been reported, in which nucleophilic o -arylation and a-alkylation of ketones is effected by polarity inversion of V-alkoxyenamines, without isolation of enamines or imines being necessary. The mild conditions for a-arylation do not require transition-metal species. ... 

Negishi coupling of jV-ethynylzinc tosylamides derivatives 92, prepared from 1,1-dichlorovinylamide 91 with aryl iodides in the presence of Pd2(dba)3 and triphenylphosphine afforded A-aryl and A -alkyl arylynamides 93. ... 

Miyoshi T, Miyakawa T, Ueda M, Miyata O (2011) Nucleophilic a-arylation and a-alkylation of ketones by polarity inversion of A-alkoxyenamines entry to the umpolung reaction at the a-carbon position of carbonyl compounds. Angew Chem Int Ed 50 928-931... 

The Fittig Reaction, in which sodium reacts with a mixture of an aryl and an alkyl halide, forming the sodium halide and the corresponding hydrocarbon ... 

Esters Saturated Aryl and a,/3-unsaturated Diesters Oxalates Phthalates C=C—CO—o— Carbamates 1741-1725 1727-1714 1763-1761 1738-1728 1716-1708 1694-1688 Alkyl branching on carbon adjacent to C=0 lowers frequency by 5-15 cm k... 

Both methyl aryl and methyl alkyl ethers are cleaved under these conditions. A methylenedioxy group, used to protect a catechol, is cleaved under similar conditions in satisfactory yield methyl and ethyl esters are stable (0-20°, 2 h). °... 

A number of 2-aryl and 2-alkyl derivatives of 5,6-dihydro-l,3-4i/-oxazine have been prepared in a similar An analogous re-... 

Similar conclusions were reached for sulfoxides 157. Conformation 158 was preferred for (RS/SR)-157 but with some contribution from conformer 159. The (RR/SS) dias-tereomers preferred the reverse conformer 161 was preferred to 160161. An attractive force between Ph/Ar and Ph/R was thought to be the primary factor in determining the conformational preference of sulfoxides 152 and 157. MM2 calculations were carried out on a series of molecules of general structure PhCHR—X—R with X equal to CHOH, C=0, S and S=0151. The main conformers of these molecules have the Ph (or aryl) and R (alkyl) groups gauche. The calculations supported the existence of CH-tr attractive interactions with minor contributions from other effects. 

The direct reductive amination (DRA) is a useful method for the synthesis of amino derivatives from carbonyl compounds, amines, and H2. Precious-metal (Ru [130-132], Rh [133-137], Ir [138-142], Pd [143]) catalyzed reactions are well known to date. The first Fe-catalyzed DRA reaction was reported by Bhanage and coworkers in 2008 (Scheme 42) [144]. Although the reaction conditions are not mild (high temperature, moderate H2 pressure), the hydrogenation of imines and/or enam-ines, which are generated by reaction of organic carbonyl compounds with amines, produces various substituted aryl and/or alkyl amines. A dihydrogen or dihydride iron complex was proposed as a reactive intermediate within the catalytic cycle. 

The basicities of some phosphinamides (84) have been measured and the acid-catalysed hydrolysis studied. Unsubstituted and A -alkyl derivatives follow an A2 mechanism of reversible protonation followed by ratedetermining water attack. However, the rates for the A -aryl derivatives follow Hq (but with a slope of 0.5), and an A mechanism was suggested as most consistent with this fact and the solvent isotope effect. The anomalous dependence on Ho, together with the large negative value of A5, while not necessarily excluding an ionization mechanism, leaves the question in some doubt. 

In a separate study, Ohberg and Westman applied the same PS-DMAP in a one-pot microwave-induced base-catalyzed reaction of N-aryl and N-alkyl amino acids (or esters) and thioisocyanates for the library synthesis of thiohydantoins (Scheme 7.115) [136]. Thiohydantoins are of interest due to their ease of preparation and the range of biological properties associated with this heterocyclic ring system. The use of PS-DMAP as the base in this reaction gave slightly lower yields compared to when triethylamine (TEA) was used, but it resulted in a cleaner reaction mixture and an easier purification procedure. Cyclizations of a number of N-substituted... 

Vinyl cations of type 28 with a-aryl or a-alkyl substituents and two P-silyl groups and with an anion of very low nucleophilicity can be generated at room temperature in non-coordinating solvents from 30 by a Si-H to C-H hydride transfer reaction. For 29 (R = t-butyl), an X-ray structure determination has been reported (43, 52, 53). 

Di-2-pyridyl sulphite (343) (from 2-pyridone and thionyl chloride in the presence of triethylamine) transforms primary aliphatic and aromatic amines RNH2 into N-sulphinylamines RN=S=0 and it dehydrates amides ArCONH2 to aryl cyanides, aldehyde oximes RCH=NOH (R = Cxlf 7. 4-MeOCgH4 or PhCH=CH) to the cyanides RCN and A-alkyl- and TV-ary Iformamides RNHCHO to isocyanides RNC. Aliphatic and aromatic... 

A viable iron carbonyl-mediated reduction process converts acid chlorides and bromoalkanes into aldehydes [3, 6]. Yields are high, with the exception of nitro-benzoyl chloride, and the procedure is generally applicable for the synthesis of alkyl, aryl and a,(i-unsaturated aldehydes from the acid chlorides. The reduction proceeds via the initial formation of the acyl iron complex, followed by hydride transfer and extrusion of the aldehyde (cf. Chapter 8). 

Perhaloalkanes have been found to scramble halogen atoms via consecutive halophilic reactions following carbanion generation by halophilic attack by base. S l reaction of an allylsilane has been applied in a stereocontrolled synthesis of ( )-dihydronepetalactone, and functionalized aryl and arylmethyl carbanions have been generated by reductive cleavage of aryl and arylmethyl alkyl ethers by electron transfer from alkali metals. ... 

Finally, addition of the carbanions derived from 83 to non-enolizable aldehydes is a facile process. Aryl and tertiary alkyl aldehydes gave trimethylsilyl allyl ethers 85 by a [1,4]-Brook isomerization (equation 30). The stereochemistry of the intermediate alkoxides 84 dramatically influences the reaction conditions required . 

This procedure demonstrates a particularly effective method for controlling the relative and absolute stereochemistry of the aldol reaction. It is quite general in scope. Alkyl-, aryl, and a,6-unsaturated aldehydes all give good results. In addition to chiral propionates, a range of related aldol reactions may be carried out. For example, the analogous aldol reactions of thioalkyl, benzyloxy, or haloacetate, as well as succinate- and crotonate-derived carboximides, have been reported. 

Of course, the cleavage reactions of both 2-aryl- and 2-alkyl aziridines are stereoselective because only the trans-diastereomers of the corresponding regioisomers 1 and 2 are formed. In other words, 2-aryl substituted aziridines showed opposite regioselectivity to 2-alkyl aziridines. With bicyclic aziridines, exclusive formation of the trans diastereomer is observed in the case of symmetric bicyclic aziridines. Unsymmetrical aziridines such as styrene, octene, and undecene aziridines produce a minor amount of the other regioisomer. 

The immediate precursor of pentachlorothiophenol was assumed to be S-(PCP)Cys. Cysteine C-S lyase enzymes that convert S-aryl and S-alkyl derivatives of cysteine to pyruvate and a thioalcohol have been detected in some plant species (24,. When the... 

Polyakov VA, Nelen MI, Nazarpack-Kandlousy N, Ryabov AD, Eliseev AV. Imine exchange in 0-aryl and 0-alkyl oximes as a base reaction for aqueous dynamic combinatorial libraries. A kinetic and thermodynamic study. J Phys Org Chem 1999 12 357-363. 

Synthesis of a new dipyrido-l,4-thiazine 328 has been described involving a Smiles rearrangement, and A -alkylation, arylation and heteroarylation of 328 have been repotted as well as its promising anti-tumor activity <2007H(71)1347>. Phenothiazine derivatives such as 329 and 330 have been developed for use in dye-sensitized solar cells <2007CC3741>. 

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