Rearrangement ambident nucleophiles

In a method for propargylating an alkyl halide without allylic rearrangement, the halide is treated with lithio-l-trimethylsilylpropyne (122) which is a lithium compound protected by an SiMca group.Attack by the ambident nucleophile... 

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). 

However, when it comes to thiopyrones an enormous range of substituents is known and almost any of the methods of ring synthesis outlined above may be used. It is especially easy to set up ambident nucleophilic species such as (143) which may be S-alkylated to (144). Thermolysis isomerizes such compounds to the 4,6-bis(alkylthio) analogues the rearrangement has been thoroughly investigated (67JOC3140). 

A major distinction for nucleophilic reactions with ambident anions is whether they proceed with kinetic or thermodynamic control.80 N-Substituted saccharins (10) should be thermodynamically more stable because of amide character than the isomeric pseudosaccharin (3) of imidate structure. In fact 3 may be rearranged thermally to 10 in an irreversible reaction.96 The threshold for thermodynamic control appears to be lowered for electrophiles with multiple bonds, e.g., formaldehyde, reactive derivatives of carboxylic acids, but also quaternary salts of N-heterocyclic compounds.80 It will be seen that in those cases substitution indeed occurs at the nitrogen, not necessarily through thermodynamic control. 

Other aspects of nucleophilicity toward vinyl cations are the site of capture of ambident ions and the easy intramolecular cyclization by o-methoxy and o-thiomethyl substituents on a P ring. The extensively studied P-aryl rearrangement across the double bond could be regarded as intramolecular substitution by the aryl ring, and data are available on the relative rate of rearrangement and capture by the solvent (69, 70). These topics are not discussed here for lack of space but should be addressed in a more complete discussion of the nucleophilicity. 

---