Mechanistic Study on the Cleavage and Reorganization of C(sp³)H and CN Bonds in Carbodiimides: Synthesis of 1,2‐Dihydrothiopyrimidines and 2,3‐Dihydropyrimidinthiones through Four‐Component Coupling

Abstract

This study sheds light on the cleavage and reorganization of C(sp(3))-H and C=N bonds of carbodiimides in a three-component reaction of terminal alkynes, sulfur, and carbodiimides by a combination of methods including 1) isolation and X-ray analysis of six-membered-ring lithium species 2-S, 2) trapping of the oxygen-analogues (B-O and D-O) of both four-membered-ring intermediate B-S and ring-opening intermediate D-S, 3) deuterium labeling studies, and 4) theoretical studies. These results show that 1) the reaction rate-determining step is [2+2] cycloaddition, 2) the C=N bond cleavage takes place before C(sp(3))-H bond cleavage, 3) the hydrogen attached to C6 in 2-S originates from the carbodiimide, and 4) three types of new aza-heterocycles, such as 1,2-dihydrothiopyrimidines, N-acyl 2,3-dihydropyrimidinthiones, and 1,2-dihydropyrimidinamino acids are constructed efficiently based on 2-S. All results strongly support the idea that the reaction proceeds through [2+2] cycloaddition/4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing as key steps. The research strategy on the synthesis, isolation, and reactivity investigation of important intermediates in metal-mediated reactions not only helps achieve an in-depth understanding of reaction mechanisms but also leads to the discovery of new synthetically useful reactions based on the important intermediates.

Mechanistic Considerations of the Catalytic Guanylation Reaction of Amines with Carbodiimides for Guanidine Synthesis

“…Metal-catalyzed C–N bond formation by N–H bond activation to construct N-containing compounds is one of the most important chemical transformations in modern organic synthesis. − The catalytic guanylation reaction of amines with carbodiimides (hereafter denoted the CGAC reaction), which is also known as catalytic addition of an amine N–H bond to the CN double bond of carbodiimides (RNCNR′, which has been applied widely in organic synthesis − ) or hydroamination of carbodiimides, can be a straightforward and atom-economical route via C–N bond formation to prepare substituted guanidines (RNC­(NR′R″)­NHR). It is well-known that guanidine derivatives are an important class of N-containing compounds which may be utilized as building blocks in various drugs (Scheme ), natural products, agrochemicals, sweeteners, explosives, etc., as base catalysts in organic synthesis, and also as supporting ligands for various metal complexes. − Although this direct guanylation reaction of primary aliphatic amines with carbodiimides can be performed under rather harsh conditions without catalyst, the guanylation reaction of aromatic amines or secondary amines cannot be achieved without suitable catalysts, owing to their decreased nucleophilicity.…”

Insertion/Rearrangement Reactivity of a Lutetacyclopentadiene towards N,N′‐Diphenylcarbodiimide: Cooperative Effect of the Metal Center, Concentration of LiCl, and Solvent

“…This result indicatest hat one C=Nd ouble bond of one mole-cule of DPC was cleaved, thereby releasing a" C =NPh" species into the system. Although several examples of C=Nb ond cleavage in carbodiimides have been reported, [6] this is the first example of C=Nc leavage by al anthanide complex. This cleavage instigated the search for the missing "C=NPh" species.…”

“…The pentadentate N 5 dianionic linker ligand is composed of at ridentate N,N,N unit and ab identate N,N unit. The organic skeleton of the N 5 dianion can be described as aNbridged diguanidinate dianion, which formsafused [4,4,6] ring on incorporation of Lu and Li centers. [5] Only five nitrogen atoms were incorporated into the final complex 4,a lthough three molecules of DPC reactedw ith 1.…”

“…The major product was shown to be 4 by comparing the in situ NMR spectra with those of pure 4.T he other product could be crystallized from the mixture and its structure was determined to be that of 6.C omplex 6 could be obtained specifically by using Et 2 O, benzene, or toluene rathert han THF as solvent (Scheme 2d). Complex 6 precipitated from Et 2 Oa sayellow powderd uring the reaction, and pure 6 was easily collected by removing the Et 2 Os olution.D iene resonances were present in the 1 Ha nd 13 CNMR spectra of 6.X -ray analysis of 6 revealed that it is composed of two parts:t he Cl-bridged moiety [LuClLi] and the N 4 dianionic ligand.T he skeleton of the Clbridged moiety [LuClLi]i ss imilar to that of the corresponding moiety observed in 1.T he N 4 dianionic ligand, which contains a1 ,6-dihydropyridine ring, is composed of ad ienem oiety and two molecules of PhN=C=NPh and can be viewed as at ridentate pincer ligand.Afused [4,5,6] ring is formed by the coordination of the N 4 dianionic ligand to the Lu center.T his structure indicates that one trimethylsilyl (TMS) group on the diene moiety migrates to the nitrogen atom that is not coordinated to the Lu center. The resultingc oupling of the diene moiety and two molecules of DPC, as wella st he 1,3-silyl shift, are in sharp contrast to that observed in the 1:3r eactiono f1 with DPC for the formation of 4,i nw hich the C=Nd oubleb onds in DPC are cleaved and the diene moiety is released.…”

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

“…Introduction 2-Phenylmalonic acid (1) and its esters are useful and versatile intermediates in the synthesis of many practically important compounds, e.g., pharmacologically active substances [1][2][3][4][5], in asymmetric synthesis and catalysis [6][7][8], as precursors of heterocyclic compounds [9][10][11], as ligands in coordination chemistry [12][13][14][15][16] and for other applications [17,18]. Incorporation of fluorine atoms into an organic molecule is known to be one of the most powerful tools for fine tuning of chemical and physical properties [19,20].…”