Addition of N-nucleophiles

Interesting examples of the addition of N-nucleophiles to nitrile oxides are syntheses of chelated Z-amidoxime, N-[2-(dimethylaminomethyl)phenyl]mesitylene-carboamidoxime (118), and pyranosyl amidoximes (119) from the respective nitrile oxides and amines. Aromatic aldoximes undergo unusual reactions with chloramine-T (4 equiv, in refluxing MeOH). N-(p-toly 1 )-N-(p-tosy 1 )benzamides are formed via addition of 2 equiv of chloramine-T to the intermediate nitrile oxide followed by elimination of sulfur dioxide (120). 

The Michael addition of N-nucleophiles to a./ -unsaturated carbonyl compounds is of obvious synthetic importance, e.g. for the preparation of / -amino acids [50a]. Several metal-containing catalysts have been devised, e.g. the chiral Al-salen... 

A similar strategy has been investigated by Barco et al. in their approach to the synthesis of piperidin-4-one derivatives 461 (Scheme 69). Starting from Merrifield-SH resin, Barco et al. prepared 4-benzylsulfonyl-l-triphenyl-phosphoranylidene-2-butanone 457 via addition of butanone/AcOH, oxidation of the sulfide to sulfone and selective bromination of the terminal methyl group. After reaction with aldehydes 458 to a. S-unsaturated ketones 459 a cyclization-elimination process occurs via addition of N-nucleophiles like benzylamine 460. 

Figure 7.31 Syntheses initiated through addition of N-nucleophiles to f Cfthiocyanate 7.2.5 Triethyl [ C]Orthoformate [H C(OEt)3]...

The addition-elimination mechanism uses one of the vacant n orbitals for bonding interaction with the nucleophile. This permits addition of the nucleophile to the aromatic ring without displacement of any of the existing substituents. If attack occurs at a position occupied by a potential leaving group, net substitution can occur by a second step in which the leaving group is expelled. 

Conjugate addition of strong nucleophiles to the >C=N—C=C< moiety, followed by ring opening of the resulting saturated 5 4H)-oxazolone. Thus, 57 reacts with simple or peptidic amino acid esters [Eq. (31)]. Similarly, 62 gives 63 in methanolic 7i-propylamine, and... 

The volumes of activation for some additions of anionic nucleophiles to arenediazonium ions were determined by Isaacs et al. (1987) and are listed in Table 6-1. All but one are negative, although one expects — and knows from various other reactions between cations and anions — that ion combination reactions should have positive volumes of activation by reason of solvent relaxation as charges become neutralized. The authors present various interpretations, one of which seems to be plausible, namely that a C — N—N bond-bending deformation of the diazonium ion occurs before the transition state of the addition is reached (Scheme 6-2). This bondbending is expected to bring about a decrease in resonance interaction in the arenediazonium ion and hence a charge concentration on Np and an increase in solvation. 

Iminium-catalyzed nucleophilic addition of N-methylindole to 2-hexenal, followed by enamine-catalyzed formation of product Star polymer encapsulation... 

A rather complex reactivity towards the cyclopropenone system is exhibited by N-nucleophiles. Thus, ammonia reacts with diphenyl cyclopropenone to yield either the enamino aldehyde 323222> or a mixture of the cis and trans isomeric diphenyl azetidinones 522223 depending on the reaction conditions these products result from primary addition of the nucleophile at C,(2 ... 

The irradiation of 5-amino-l,2,4-oxadiazoles 60 in the presence of nucleophilic nitrogen sources (primary amines, ammonia or hydrazine) produced l,2,4-triazolin-5-ones 62, a process which proceeds via cleavage of the N-O bond and addition of the nucleophile to form the intermediate 61 (Scheme 3) <1996JOC8397>. 

An alternative means of activating an activated r/>3-C-H bond is by the addition of a nucleophile to an allylic species as in aminations using catalytic amounts of Pd(n) (Equation (34)).43... 

Two structurally unrelated immunosuppressant drugs, cyclosporin A and FK506, have been shown to bind to separate proteins, which have in common the ability to catalyse the interconversion (8) of the cis and trans rotamers of peptidyl-proline bonds of peptide substrates. A profound change in the conformation, and hence the shape and binding properties of the protein, may result. The mechanism of this isomerization appears, on the basis of recent work (Rosen et al., 1990 Van Duyne et al., 1993 Albers et al., 1990), to involve simple twisting about the amide bond, rather than such alternatives as conversion to a C-N single bond by addition of a nucleophile to C=0.y The proteins which catalyse the reaction may be... 

NDA derivatization has also been automated for analysis of amino acids in brain tissue and microdialysates (Shah et al, 1999). NDA reacts with primary amines in the presence of cyanide to form a highly stable N-substituted l-cyanobenz[/] isoindole (GBI) derivative. Addition of a nucleophile, such as cyanide, hydrogen sulphite, isothiocyanate, or 2-mercaptoethanol, is essential for the formation of the derivative. 

With [ N2]hydrazinium hydrogen sulfate and potassium hydroxide, the 2, 3, 5 -tri-0-acetyl-l-( N-amino) (3- N) inosine 54 is obtained (Scheme III.29). The reaction follows the same reaction pathway as described in Scheme III.28 addition of the nucleophile at C-6, ring opening between C(6) and N(l), and ring closure with elimination of nitrous oxide and water. This Sn(ANRORC) reaction provides us with an good entry to N-ring-labeled purines. 

Concerning the mechanism of the rearrangement, it is proposed to involve the addition of the nucleophilic nitrogen of the 1,3-ambident nucleophiles to C-6 (see Section III,A,2,a). This covalent adduct is in equilibrium with the open-chain diamidino compound 83 (R = OCH3, SCH3). Cycliza-tion into 84, followed by a base-catalyzed fragmentation of the nitrogen-carbon bond at N-3 and expulsion of the thiomethyl or methoxy anion, yields the 2-amino-4(5)-phenylpyrimidines (Scheme III.47). 

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