Alkylation carbonyl compound nitrogen derivatives

In the oxaziridines (1) ring positions 1, 2 and 3 are attributed to oxygen, nitrogen and carbon respectively. The latter almost always is in the oxidation state of a carbonyl compound and only in rare cases that of a carboxylic acid. Oxaziridinones are not known. The nitrogen can be substituted by aryl, alkyl, H or acyl the substituent causes large differences in chemical behavior. Fused derivatives (4), accessible from cyclic starting materials (Section 5.08.4.1), do not differ from monocyclic oxaziridines. 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Condensation of ethyl anthranHates with isothiocyanates provides entry to a closely related compound in which the carbonyl at the 2 position is replaced by a thione. The sequence starts with the alkylation of pyrrolidine nitrogen in (92-1) with 2-bromoethylamine. Reaction of the primary amine in the product (92-2) with thiophosgene leads to the isothiocyanate derivative (92-3). Reaction of that reactive intermediate with methyl anthranilate (92-4) leads initially to the transient... 

Deprotonation of BSMA imines followed by trapping with an electrophile of the intermediate anion has been described (see Section IV.C.4). However, when these imines derive from conjugated carbonyl compounds, attack of the base takes place at the end of the conjugated system to give delocalized bis(allyl) anion that could be alkylated or silylated in the (3-position from the nitrogen.227... 

Abstraction of a proton from the methylene of an MSMA leads to an a-silyl-a -nitrogen carbanion that can be silylated or alkylated (see Section IV.C) when reacted with a carbonyl compound vinyl amino derivatives were readily obtained.157,158... 

Whereas isolated imines are relatively unstable and readily undergo hydrolysis to form carbonyl compounds, alkylated imines and imino derivatives are found as stable compounds in a variety of situations. Thus a number of nitrogen derivatives of aldehydes and ketones, such as the oxime, semicarbazone and hydrazone, contain an imino fragment. 

Asymmetric Alkylations. The use of nitrogen derivatives of carbonyl compounds (imines, imides, amides, sultams, oxazo-lines) is often the most efficient procedure for achieving a-alkylations. Chiral auxiliaries bearing heteroatoms in a 1,2-relationship appear to work best, as they have chelation sites for the metal cation. High levels of asymmetric induction can thus be achieved due to the system rigidity. Cyclic ketones have been alkylated via the lithiated enamine formed from L-f-leucine f-butyl ester (eq 1). High enantiomeric excesses and predictability of absolute configuration make this method attractive. 

ALKYLATIONS OF CARBONYL COMPOUNDS VIA THEIR NITROGEN DERIVATIVES... 

J.l Regiochemistry and Stereochemistry of Alkylations of Nitrogen Derivatives of Carbonyl Compounds... 

There have been several papers dealing with the oxidation reactions of nitrogen and sulfur-based compounds. Hindered amines, such as substituted 2,2,6,6-tetramethylpiperidines, are easily oxidized by electron-transfer reactions to the corresponding cation, by the sulfate radical anion, and by sensitized electron transfer to carbonyl triplets. Radicals derived from tertiary piperidines were observed directly by optical spectroscopy and deprotonated to a-alkylamine radicals. The amine radical cation derived from secondary piperidines deprotonated to give aminyl radicals. In the presence of oxygen, both classes were oxidized to give nitroxyl radicals, but by different proposed mechanisms. Both oxidation and fragmentation pathways have been observed in the photochemical reaction of alkyl phenyl sulfides with tetranitromethane. The oxidation of various A-(arylthio)-4-substituted-2,6-diarylanilines (18) with PbOa yielded, in most cases, persistent radicals that could... 

As mentioned above, a range of enantioselective transformations have been established using chiral phosphoric acids via the activation of imines and related nitrogen-substituted substrates. In contrast, the activation of carbonyl compounds, including a,P-unsaturated carbonyl compounds, by chiral phosphoric acids has been limited. In 2008, Zhou, He, and coworkers achieved the asymmetric Friedel-Crafts alkylation reaction of indole derivatives with 1,3-diaryl a,p-unsaturated... 

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