Reactivity dialkylamino groups

Neunhoeffer and Lehmann have shown that it is possible to reverse the diene character of the 1,2,4-triazine ring by introducing alkoxy or dialkylamino groups into the ring. Alkoxy-, dialkoxy- and dialkylamino-1,2,4-triazines are therefore less reactive toward ynamines but they still react with these dienophiles. Bis(dialkylamino)-, trialkoxy- and tris(dialkylamino)-l,2,4-triazines (425) behave as electron-rich dienes and give cycloaddition reactions with acetylenedicarboxylate (426) but not with ynamines. Compounds (425) and (426) afford the 2,4-bis(dialkylamino)pyrimidine-5,6-dicarboxylates (427) (77LA1413). 

The tendency of Ti reagents like Ti(NR2)4 to release the yVJV-dialkylamino group is conveniently exploited to temporarily inactivate a carbonyl function which is fairly reactive (e.g. an aldehyde),thus enabling a second, less reactive carbonyl fiinction e.g. a ketone), to react with another nucleophilic reagent. This leads to a sort of reverse chemoselectivity which is highly effective in discriminating between different carbonyl compounds, as well as between carbonyls having different steric environments. 

Substituents in the alkyl chain of alkyl aluminum compounds, such as halogens, alkoxy, alkylmercapto, or dialkylamino groups, have varying effects on the stability of the aluminum alkyls to extents which depend on the position of the group in relation to the aluminum. Interaction between the substituents and aluminum leads to activation of both the A1—C and the C-substituent bonds. If, in the case of dialkyl halomethylalanes, the substituent (Cl, Br, or I) and the aluminum are linked to the same carbon atom, the compound is especially reactive. These compounds, since their etherates are stable, may be prepared readily in ethereal solution from dialkyl aluminum halides and diazomethane 97, 98) ... 

This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Bis(dialkylamino)sulfur difluorides, RjNSFaNRj, albeit less reactive than DAST, also substitute hydroxyl groups with fluorine [95, 97 /52]... 

Recently, Aumann et al. reported that rhodium catalysts enhance the reactivity of 3-dialkylamino-substituted Fischer carbene complexes 72 to undergo insertion with enynes 73 and subsequent formation of 4-alkenyl-substituted 5-dialkylamino-2-ethoxycyclopentadienes 75 via the transmetallated carbene intermediate 74 (Scheme 15, Table 2) [73]. It is not obvious whether this transformation is also applicable to complexes of type 72 with substituents other than phenyl in the 3-position. One alkyne 73, with a methoxymethyl group instead of the alkenyl or phenyl, i.e., propargyl methyl ether, was also successfully applied [73]. 

The hydroxy group is far more reactive to (dialkylamino)trifluoro-A4-sulfanes than most other functional groups. Thus, at low temperatures a hydroxy group can be selectively fluorinated in the presence of another functional group. This, coupled with the inertness of (dialkylamino)-trifluoro-A4-sulfanes towards most protection groups, and the mild reaction conditions required has enabled a vast array of functionalized fluorinated compounds to be synthesized, for example, carbohydrates,24-29,31 nucleosides,30 and steroids32 35 (see Table 3). 

A quantitative assessment of the effects of head group bulk on, S k2 and E2 reactions in cationic micelles has been made.148 The kinetics of the acid-catalysed hydrolysis of methyl acetate in the presence of cationic, anionic, and non-ionic surfactants has been reported on.149 The alkaline hydrolysis of -butyl acetate with cetyltrimethylammonium bromide has also been investigated.150 The alkaline hydrolysis of aromatic and aliphatic ethyl esters in anionic and non-ionic surfactants has been studied.151 Specific salting-in effects that lead to striking substrate selectivity were observed for the hydrolysis of /j-nitrophenyl alkanoates (185 n = 2-16) catalysed by the 4-(dialkylamino)pyridine-fimctionalized polymer (186) in aqueous Tris buffer solution at pH 8 and 30 °C. The formation of a reactive catalyst-substrate complex, (185)-(186), seems to be promoted by the presence of tris(hydroxymethyl)methylammonium ion.152... 

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