FORMATION AND ALKYLATION

Mazur " obtained 2a-alkyl-5a-H (3) or 4 -alkyl-5 -H products (6) by direct alkylation of either 5a-H (1) or 5 -H-3-keto steroids (4) with alkyl halides under basic conditions. In general, formation and alkylation of the more stable enolate ion is observed in this procedure. 

By Production of Azepinium Salts, Protonation, Complex Formation and Alkylation... 

Alkylation of dianions occurs at the more basic carbon. This technique permits alkylation of 1,3-dicarbonyl compounds to be carried out cleanly at the less acidic position. Since, as discussed earlier, alkylation of the monoanion occurs at the carbon between the two carbonyl groups, the site of monoalkylation can be controlled by choice of the amount and nature of the base. A few examples of the formation and alkylation of dianions are collected in Scheme 1.7. In each case, alkylation occurs at the less stabilized anionic carbon. In Entry 3, the a-formyl substituent, which is removed after the alkylation, serves to direct the alkylation to the methyl-substituted carbon. Entry 6 is a step in the synthesis of artemisinin, an antimalarial component of a Chinese herbal medicine. The sulfoxide serves as an anion-stabilizing group and the dianion is alkylated at the less acidic a-position. Note that this reaction is also stereoselective for the trans isomer. The phenylsulfinyl group is removed reductively by aluminum. (See Section 5.6.2 for a discussion of this reaction.)... 

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

Many opportunities conversely are supported by reversible reactions of QM despite the noted complications. One example includes the synthesis and chiral resolution of binaphthol derivatives by two cycles of QM formation and alkylation.77 The reversibility of QM reaction may also be integrated in future design of self-assembling systems to provide covalent strength to the ultimate thermodynamic product. To date, QMs have already demonstrated great success in supporting the opposite process, spontaneous disassembly of dendrimers (Chapter 5). 

FORMATION AND ALKYLATION OF SPECIFIC ENOLATE ANIONS FROM AN UNSYMMETRICAL KETONE 2-BENZYL-2-METHYLCY-CL0HEXAN0NE AND 2-BENZYL— 6-METHYLCYCLOHEXANONE, 52,... 

Polynitroaliphatic alcohols containing nitro groups on the carbon fi to the hydroxy functionality are less basic than their alkyl counterparts. This decreased basicity of the hydroxy group makes reactions such as esterification, acetal formation and alkylation much slower than usual, and in some cases, these reactions may not proceed without catalysts. To add to the problem, normal base catalysts cannot be used in conjunction with 2,2-dinitroalkanols and l,l,l-trinitro-2-alkanols because of their facile dissociation in alkaline solution. 

Alkylation reactions of dianions occur at the more basic carbon. This technique allows alkylation of 1,3-dicarbonyl compounds to be carried out cleanly at the less acidic position. Because, as discussed earlier, alkylation of the monoanion occurs at the carbon between the two carbonyl groups, the site of monoalkylation can be controlled by choice of the amount and nature of the base. A few examples of the formation and alkylation of dianions are collected in Scheme 1.8. 

The alkylation of enolates from some recently developed 2-oxazolidinone auxiliaries will be briefly discussed. The Diels-Alder reaction of the enantiomerically pure 3-(apocamphane-carbonyl)-2(3//)-oxazolone 13 with anthracene gives, diastereoselectively, a 97 3 ratio of diastereomeric adducts63. Recrystallization followed by removal of the apocamphanecarbonyl auxiliary and acylation gives the diastereomerically pure enantiomer 14 in good yield. Subsequent enolate formation and alkylation gives highly diastereoselective reactions and easily purified products due to the fact that the major product is readily crystallized. Thus alkylation... 

The enantiomerically pure substituted 1,2-dihydro-4(3//)-pyrimidinone 11 has been employed as a chiral auxiliary for diastereoselective alkylation reactions2. Thus, acylation, followed by enolate formation and alkylation with reactive halides such as halomethanes. (balomethyl)benzenes, 3-halopropenes and 3-halopropynes, affords the alkylation products with high diastereoselectivity (d.r. 93 7 to 99 1) . 

Fig. 5.10 Carbanion formation and alkylation via interfacial deprotonation using concentrated aqueous hydroxide solution.

Scheme 5.31. Formation and alkylation of chelate-stabilized a-oxygen and a-sulfur carbanions [55, 272-274].

Gall, M. House, H. O. The formation and alkylation of specific enolate anions from an unsymmetrical ketone 2-benzyl-2-methylcy-clohexanone and 2-benzyl-6-methylcyclohexa-none. Org. Synth. 1988, Coll. Vol. VI, 121-130. 

The thiolate-bridged diruthenium complex 101 can promote a cycloaddition reaction between propargylic alcohols and 1,3-dicarbonyl compounds to provide 3-acyM//-pyrans in excellent yield (Scheme 33). The reaction proceeds via formation and alkylation of the allenylidene complex 102 to form the vinylidene intermediate 103, which upon cyclization furnishes 4//-pyrans (Scheme 33) <2004JOC3408>. 

This section deals only with solvents whose reduction products are insoluble in the presence of lithium ions. The list includes open chain ethers such as diethyl ether, dimethoxy ethane, and other polyethers of the glyme family cyclic ethers such as THF, 2Me-THF, and 1,4-dioxane cyclic ketals such as 1,3-dioxolane and 1,3-dioxane, esters such as y-butyrolactone and methyl formate and alkyl carbonates such as PC, EC, DMC, and ethylmethyl carbonate. This list excludes the esters, ethyl and methyl acetates, and diethyl carbonate, whose reduction products are soluble in them (in spite of the presence of Li ions). Solutions of solvents such as acetonitrile and dimethyl formamide are also not included in this section for the same reasons. Figure 6 presents typical steady state voltammo-grams obtained with gold, platinum, and silver electrodes in Li salt solutions in which solvent reduction products are formed and precipitate at potentials above that of lithium metal deposition. These voltammograms are typical of the above-mentioned solvent groups and are characterized by the following features ... 

Mechanism 22-4 Base-Catalyzed Keto-EnolTautomerism 1047 Mechanism 22-5 Acid-Catalyzed Keto-EnolTautomerism 1047 22-3 Alkylation of Enolate Ions 1050 22-4 Formation and Alkylation of Enamines 1051 22-5 Alpha Halogenation of Ketones 1054... 

A milder alternative to direct alkylation of enolate ions is the formation and alkylation of an enamine derivative. An enamine (a vinyl amine) is the nitrogen analogue of an enol. The resonance picture of an enamine shows that it has some carbanion character. 

Castro A, Spencer TA. Formation and alkylation of anions of bis(methylsulfonyl.methane. J. Org. Chem. 1992 57 3496-3499. 

Oxidoalkylselenonium salts (Schemes 59-61) - - and B-oxidoalkyl selenones (Schemes 55 and 56) 9. o,i38.206 jjjg unstable too, and directly coll q>se to epoxides even at-78 C. The fonner reaction is limited to nonenolizable carbonyl compounds. In the case of acetophenone and trimethylselenonium iodide, for example, polymethylation of the carbonyl compound occurs (Scheme 122). The results can be rationalized by considering enolate formation and alkylation of the enolate by the selenonium salt. 

Fig. (20). Mechanism of radical formation and alkylation of a heme surrogate (Mnm-tetraphenyl-porphyrine) by ART as shown by Robert Meunier [96].

In contrast to liquid chromatography which is the technique of choice when considering high molecular mass constituents, gas chromatography (GC) is well-suited for the fractionation of low molecular mass species which are volatile, thermally stable and preferably neutral. Some species that do not already possess the above properties can be converted into forms that are amenable to GC. Various derivatization procedures that can be used to perform such conversions have been described by Poole and Schuette (1984). However, it Is worth mentioning that hydride formation and alkylation are the two most commonly used derivatization methods that have found application in the study of the speciation of various elements like As, Bi, Ge, Hg, Pb, Sb, Se, Sn, Te and Tl. Two points have to be considered when derivatization is performed first, the specificity of the chemical conversion second, the percentage yield of the reaction. A specific reaction is desirable in order to avoid the introduction of artefacts. Moreover, if a quantitative estimate of the amount of the original species is required, then it is essential that the extent of the conversion is known. 

For example, in a synthesis of the immunosuppressant (-)-sanglifehrin A, the alcohol 57 was converted into the chiral alcohol 58 as a single enantiomer (1.73). The procedure involves oxidation of the alcohol 57 with pyridinium chlorochro-mate (PCC) and conversion to the Evans oxazolidinone (via the mixed anhydride), followed by stereoselective enolate formation and alkylation, then reduction to remove the auxiliary. 

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