C–H Insertion by Alkylidene Carbenes To Form 1,2,3-Triazines and Anionic [3 + 2] Dipolar Cycloadditions To Form Tetrazoles: Crucial Roles of Stereoelectronic and Steric Effects

Abstract

The synthesis of 1,2,3-triazines and bicyclic tetrazoles from α-azido ketones is described. The common intermediate generated from lithiated trimethylsilyldiazomethane and α-azido ketones diverges depending on the steric bulk of the substituents. The formation of 1,2,3-triazines via a C–H insertion of alkylidene carbene to form 3-azidocyclopropene, followed by its rearrangement, is supported by density functional theory calculations. Tetrazole formation proceeds via a facile anionic [3 + 2] dipolar cycloaddition between a lithiated diazo moiety and an azido group facilitated by the chelation of a lithium ion.

Systematic Evaluation of 1,2-Migratory Aptitude in Alkylidene Carbenes

“…The above findings on electronic matching add to a previous rather fragmentary body of evidence suggesting that the absolute migratory aptitude of a given substituent is not an intrinsic property but mutually dependent on the stationary substituent, or bystander . The synthetic ramifications of the matching effect, nevertheless, are not yet completely clear.…”

Synthesis and some reactions of 5-carbmethoxymethylidene-4-oxo-1,3-thiazol-2-ylguanidine

“…Another urgent task in organic chemistry is to study the reactions of polynucleophilic compounds with polyelectrophiles which, depending on the reaction conditions utilized, can lead to the formation of various heterocyclic systems. [13][14][15][16] In this regard, amidinothiourea is a polynucleophilic substrate that, depending on the structure of the electrophile, behaves like a 1,3-N,S-, [17][18][19] 1,3-N,N- [19][20] or 1,5-N,N- 21 binucleophile. In addition, imethylacetylene dicarboxylate is widely used in organic synthesis for the construction of five-, six-, and seven-membered heterocyclic systems.…”

DFT investigation of hydrogen atom-abstraction reactions of NHC-boranes by various carbon-centered radicals: barriers and correlation analyses

“…Therefore, it is somewhat unrealistic to derive the kinetic stereoelectronic and steric effects using the charges and spin densities alone, of the energy minimum structures of the radical reactants. [33][34][35] Furthermore, the spin density distribution of the product radical directly affects its thermodynamic stability, and further affects the thermodynamic reaction energy and thermal contribution to the kinetic barrier. Therefore, it is difficult to strictly correlate the relative reactivities of the radicals to their abilities for abstracting Hatoms from the NHC-boranes using their charges and spin density distributions.…”

“…The size of the radical or its substituent may directly reect the steric hindrance faced during the radical attack. However, this sterics-based judgment is only empirical, because of the multitude of factors involved, such as the variations in the reaction trajectory, 36 stereoelectronic and steric effects, [33][34][35] reaction thermodynamics. 32 Further, when the steric and electronic hindrances are not the dominant factors related to the Habstraction kinetics, this method is completely ineffective.…”