Alkylation with Acid Derivatives

The gas-phase alkylation of toluene with alkyl chloroformates over Nafion-H was also reported to be an efficient transformation. It is interesting to compare the alkylating ability of methyl chloroformate with that of methyl alcohol on toluene under similar reaction conditions. For example, a 59% conversion with methyl chloroformate was observed,265 compared with 15% conversion with methyl alcohol. 

The gas-phase alkylation of toluene with dimethyl and diethyl oxalate over Nafion-H was also reported.265 The alkylating ability of diethyl oxalate is 

Alkylating Agent Temperature °C Isomer Distribution (%) Conversion (%) ortho meta para  

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Another catalytic application emanating from the Hieber base reaction was developed by Reppe and Vetter [108]. They showed that 1-propanol 126 could be generated by treatment of ethylene 125 with catalytic amounts of Fe(CO)5 78 under CO-pressure and basic reaction conditions (Scheme 33). Thereby, trimethylamine and V-alkylated amino acid derivatives mrned out to be optimal bases for this reaction. Like ethylene 125, propylene could be transferred mainly to 1-butanol diolefins like butadiene only reacted to monoalcohols. By employing these reaction conditions to olefins in the presence of ammonia, primary or secondary amines, mono-, di-, and trialkylamines were obtained whose alkyl chains were elongated with one carbon atom, compared to the olefins. 

Organoboranes can also be used to construct carbon-carbon bonds by several other types of reactions that involve migration of a boron substituent to carbon. One such reaction involves a-halo carbonyl compounds.20 For example, ethyl bromoac-etate reacts with trialkylboranes in the presence of base to give alkylated acetic acid derivatives in excellent yield. The reaction is most efficiently carried out with a 9-BBN derivative. These reactions can also be effected with (3-alkenyl derivatives of 9-BBN to give (3,y-unsaturated esters.21... 

In contrast to the high enantioselectivity achieved for the Z-isomeric substrates, hydrogenation of the E-isomers usually proceeds with lower rates and afford products with diminished enantioselectivities [92]. The rhodium-catalyzed hydrogenation of the - and Z-isomers, with BINAP as a ligand in THE, affords products with opposite absolute configurations [16]. Remarkably, the DuPhos-Rh system provides excellent enantioselectivity for both isomeric substrates with the same absolute configuration, irrespective of the /Z-geometry (Eqs. 1 and 2). This result is particularly important for the construction of alkyl dehydroamino acid derivatives, which are difficult to prepare in enantiomericaUy pure form. 

TABLE 7.14. 3-ALKYL ASPARTIC ACID DERIVATIVES EROM REACTION OF 5(277)-OXAZOLONES WITH YNAMINES"... 

TABLE 7.14 3-ALKYL ASPARTIC ACID DERIVATIVES FROM REACTION OF 5(2//)-OXAZOLONES WITH YNAME/ES, 149... 

The asymmetric halolactonization reactions of unsaturated L-proline amides, developed by Terashima and coworkers,184 has been extended to a-alkyl acrylic acid derivatives (equation 75 and Table 21).185 This allows for the synthesis of either enantiomer of an a-methyl-a-hydroxy acid using L-proline as the auxiliary. Less successful approaches to asymmetric induction with a chiral auxiliary include iodolac-... 

In the case ofo-methylbenzyl bromide (22), a substantial amount (34%) of an alkylated phenylpyruvic acid derivative (24) was formed along with the anticipated phenylacetic acid (23) (34). This novel double carbonylation reaction (to give 27) was later observed to a variable, but minor, ex-... 

Straight-chain alkyl carboxylic acids derived from petroleum that also have a terminal cyclohexyl or cyclopentyl group are known as naphthenic acids. They form complexes, presumably polymeric, with many transition metals, and these compounds are freely soluble in petroleum. Copper naphthenates are used as fungicides, aluminum naphthenate was used as a gelling agent in napalm, and cobalt naphthenates are used in paints. 

Azlactones have been used as nucleophiles to provide access to a variety of a-alkylated amino acid derivatives. This has been demonstrated with 3-acetoxycyclohexene and with geminal dicar-boxy lates (eq 2)." The enantiomeric and diastereoisomeric excess of the products increase with more bulky R groups. 

The gold-catalyzed aldol reaction of a-keto esters gives the corresponding oxazolines with up to 90% ee, which are converted into optically actice ) -alkyl-) -hydroxyaspartic acid derivatives (Scheme 2-55) [77]. 

New y-ethoxycarbonyl- and ot-amino-alkyl-hydroxyphosphinic acid derivatives (366) and (367) were conveniently prepared by Michael addition or Kabachnik-Fields reaction of a new precursor, benzyloxymethyl hydrogen-phosphinate (368), with a,p-unsaturated esters or imines (Scheme 94). " Phosphinic acid inhibitors (369) of Cathepsin C were synthesized by addition of methyl acrylate to the appropriate a-amino phosphinic acid and by... 

Similar information is available for other bases. Lithium phenoxide (LiOPh) is a tetramer in THF. Lithium 3,5-dimethylphenoxide is a tetramer in ether, but addition of HMPA leads to dissociation to a monomer. Enolate anions are nucleophiles in reactions with alkyl halides (reaction 10-68), with aldehydes and ketones (reactions 16-34, 16-36) and with acid derivatives (reaction 16-85). Enolate anions are also bases, reacting with water, alcohols and other protic solvents, and even the carbonyl precursor to the enolate anion. Enolate anions exist as aggregates, and the effect of solvent on aggregation and reactivity of lithium enolate anions has been studied. The influence of alkyl substitution on the energetics of enolate anions has been studied. ... 

Quirion has reported the first application of chiral carboxylic acids as activating agents and chiral inducers for a-lithiation of tetrahydroisoquinolines [67]. The diastereoselective lithiation and alkylation of acid-derived amides 78 provided 79 in 41-57% yields with moderate drs of up to 92 8 (Scheme 22). The chiral auxiliary can be removed under refluxing basic conditions (KOH/MeOH) in 60-70% yields. 

Hydrocarbon Mixtures with Alkyl Phosphoric Acid Derivatives... 

Doucet H. Suzuki-Miyaura cross-coupling reactions of alkyl-boronic acid derivatives or alkyltrifluoroborates with aryl, alkenyl or alkyl halides and triflates. Eur. J. Org. Chem. 2008 (12) 2013-2030. 

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