Y-alkylations

Those derived from isobutane are the 2-methylpropyl (isobutyl) group and the 1,1-dimethylethyl (tert-butyl) group. Isobutyl is a primar y alkyl group because its potential point of attachment is to a primary carbon. tert-Butyl is a tertiary alkyl group because its potential point of attachment is to a tertiary carbon. 

In practice, this reaction is difficult to cany out with simple aldehydes and ketones because aldol condensation competes with alkylation. Furthermore, it is not always possible to limit the reaction to the introduction of a single alkyl group. The most successful alkylation procedures use p-diketones as starting materials. Because they are relatively acidic, p-diketones can be converted quantitatively to then enolate ions by weak bases and do not self-condense. Ideally, the alkyl halide should be a methyl or prirnar-y alkyl halide. 

Few other reactions of series of substituted pyridines have been investigated extensively. Dondoni, Modena, and Todesco have measured the rate of N-oxidation of a limited series of pyridines and found a good correlation with normal u-values with a p-value of — 2.23. The A-alkylation of pyridines with alkyl iodides in nitrobenzene has been studied by Brown and Cahn and by Clarke and Rothwell. Unfortunately, the only data available are for the parent compound and for alkyl derivatives, and, since the a-values for the various alkyl groups in a given position are substantially constant, this leaves a correlation of only three independent points. However, the rates of A-alkylation of the j8- and y-alkyl derivatives are so nearly equal that it appears as if no correlation existed. Clarke and Rothwell have also studied the alkylation with allyl bromide in nitromethane at various temperatures, and in this case a more extensive series is available. The authors state that no overall Hammett correlation is obtained however, the j8-substituted derivatives fall on one straight line and the y-derivatives on another one with a different slope. The data are shown in Fig. 2. The line for the j8-compounds, p = — 2.53 0.31, r = 0.95, is seen not to be very good the line for the y-derivatives, p = — 1.42 0.06, r = 0.99, is much more satisfactory. It does not seem likely that the discrepancy is due to the intervention of resonance effects, since in this case one would expect the correlation for the y-derivatives to be poorer than that for the j8-analogs. More extensive studies with a wider variety of substituents would seem very desirable. 

In summary, the leaving groups which coordinate strongly to copper give the y-alkylation product even in the presence of a sterically bulky substituent at the y-position. 

Organocopper-boron trifluoride (RCu BF3) reacts with allylic alcohols, such as 3-phenyl-2-propenol, 2-butenol, 3-buten-2-ol, 2,4-hexadienol, 3-methyl-2-butenol, to give the y-alkylation... 

Tabic 2. Conjugate Addition to y-Alkyl-a./l-Unsaturaled Carbonyl Derivatives... 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

The extent of restricted rotation about the amide band of (38) was used to compare the electron-withdrawing process of phosphonium salts (38, Y = alkyl) and chalcogenides (38, Y = O or S) with the more conventional electron-withdrawing groups. These phosphorus groups were found to exert a — A7 effect comparable with that of a nitro-group. 

Deprotonation of allylic aryl sulfoxides leads to allylic carbanions which react with aldehyde electrophiles at the carbon atom a and also y to sulfur . With benzaldehyde at — 10 °C y-alkylation predominates , whereas with aliphatic aldehydes at — 78 °C in the presence of HMPA a-alkylation predominates . When the a-alkylated products, which themselves are allylic sulfoxides, undergo 2,3-sigmatropic rearrangement, the rearranged compounds (i.e., allylic sulfenate esters) can be trapped with thiophiles to produce overall ( )-l,4-dihydroxyalkenes (equation 24). When a-substituted aldehydes are used as electrophiles, formation of syn-diols 27 occurs in 40-67% yields with diastereoselectivities ranging from 2-28 1 (equation 24) . ... 

Scheme 1.8 shows some intramolecular enolate alkylations. The reactions in Section A involve alkylation of ketone enolates. Entry 1 is a case of a-alkylation of a conjugated dienolate. In this case, the a-alkylation is also favored by ring strain effects because y-alkylation would lead to a four-membered ring. The intramolecular alkylation in Entry 2 was used in the synthesis of the terpene seychellene. 

X-ray fluorescence spectra of tertiary phosphines (52 Ar = Ph, Y = alkyl) indicated that when the PY2 group is in the best geometry for p-it conjugation the interaction is still only 25% of that of the dimethylamino group.131... 

H NMR and 2H NMR spectra of fractionated coal products from El0 and El9 were recorded and analyzed to determine and 2H composition for each structural position. In our study, y y and 2Hx,v are defined as the fraction of the JH and 2H determined from the integrals of the NMR spectra of a given soluble fraction where y equals HS, BS or BMS and x = y-alkyl, 0-alkyl, a-alkyl or aromatic structural positions. The spectral range of the NMR integrations are given in Table V. 

It was found that treatment of a mixture of 120 and 121 with tris(diethylamino-sulfonium) trimethyldifluorosilicate [TASF(Et)] resulted in smooth addition-elimination to the naphthoquinone to form the y-alkylation product 125 (85 %). TASF(Et) is a convenient source of soluble, anhydrous fluoride ion [47]. It is believed that exposure of 121 to TASF(Et) results in fluoride transfer to generate a hypervalent silicate anion, as depicted in structure 124. The transfer of fluoride between TASF(Et) and 121 may be driven by stabilization of the anionic species 124 by delocalization of the carbon-silicon bond into the LUMO of the unsaturated ketone. 1,4-Addition-elimination of this species to the naphthoquinone 120 would then form the observed product. 

The 1,4-diazepane 87 has been used as a neutral 6-electron ligand for the support of cationic Group 3 metal (Sc,Y) alkyl catalysts <06CC3320>. 

Cp,Cp-IndoNOP 18 [15 p], have provided excellent enantioselectivity and reactivity for the enantioseiective hydrogenation of a-, / -, and y-alkyl amino ketone hydrochloride salts. 

Another formal total synthesis of ( )-yohimbine has been worked out by Wenkert et al. (229) by preparing O-methylhexadehydroyohimbine (420), which was first prepared by Kametani and co-workers (224-226) as a key intermediate toward ( )-yohimbine. In Wenkert s approach, pyridinium salt 427 was y-alkylated with acetoacetic ester anion. The product 428 then underwent intramolecular condensation, affording tetracyclic quinone 429. Methylation of 429... 

When thioxo (or thiol) derivatives (as part of a thiourea function incorporated into the heterocyclic system) are present, effective. Y-alkylation is observed. Thus, the 3-heteroaryl-substituted [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazole-6(5//)-thiones 37 dissolved in sodium hydroxide solution react with alkyl halides to afford the corresponding 6-alkylthio derivatives 38 (Equation 4) <1992IJB167>. The mesoionic compounds 39, inner salts of anhydro-7-aryl-l-methyl-3-methylthio-6-sulfonyl-[l,2,4]triazolo[4,3-A [l,2,4]triazolium hydroxides, are methylated with methyl iodide to give the corresponding quaternary salts 40 (Equation 5) <1984TL5427, 1986T2121>. 

Derivatives of diaminoanthrarufin (3.77 X = Y = H) and its 1,8-dihydroxy-4,5-diamino isomer (diaminochrysazin) have been among the most widely used anthraquinone dyes for ester fibres. For example, methylation of diaminoanthrarufin gives Cl Disperse Blue 26, a mixture of several components. Study of the pure N-alkylated derivatives from the base confirmed that monosubstitution (3.77 X = H, Y = alkyl) gives mid-blue dyes with excellent dyeing properties and acceptable fastness on polyester, but the bis-alkyl dyes (3.77 X = Y = alkyl) are greener and inferior in application properties. Mixtures of the unsubstituted base with alkylated components, as obtained industrially, were especially advantageous for build-up to heavy depths, however [93]. 

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