Enediynes, enyne‐allenes, their reactions, and beyond

Abstract

Enediynes undergo a Bergman cyclization reaction to form the labile 1,4-didehydrobenzene (p-benzyne) biradical. The energetics of this reaction and the related Schreiner-Pascal reaction as well as that of the Myers-Saito and Schmittel reactions of enyne-allenes are discussed on the basis of a variety of quantum chemical and available experimental results. The computational investigation of enediynes has been beneficial for both experimentalists and theoreticians because it has led to new synthetic challenges and new computational methodologies. The accurate description of biradicals has been one of the results of this mutual fertilization. Other results have been the computer-assisted drug design of new antitumor antibiotics based on the biological activity of natural enediynes, the investigation of hetero-and metallo-enediynes, the use of enediynes in chemical synthesis and materials science, or an understanding of catalyzed enediyne reactions. C 2013 John

Mechanism of the Intramolecular Hexadehydro-Diels–Alder Reaction

“…This is in contrast, then, to the Bergman cycloaromatization of an enediyne, 30 which generates a diradical p -benzyne intermediate that is incapable of further closure owing to the instability of what would be a “Dewar benzyne” product. 31 The intramolecular HDDA is also in contrast with the Myers-Saito 32 and Schmittel 33 cycloaromatizations of enyne-allenes, which lead to α,3-didehydrotoluene and extracyclic fulvenoid diradical intermediates, respectively, 31e,34 and with the cycloaromatization of the enyne-cumulene neocarzinostatin chromophore, which leads to a 1,5-didehydroindene. 35 In none of these other cases are the radical centers able to react (intramolecularly) with one another to form a new bond (and ring): geometric constraints prevent such a closure.…”

Recent advances of the Bergman cyclization in polymer science

“…The therapeutic applications of these enediyne antitumor antibiotics have also triggered a series of research efforts in connection with enediyne chemistry including quantum chemical theory, thermodynamics, and kinetics studies of the Bergman cyclization [14]. Based on these studies, the activation barrier of the Bergman cyclization is influenced by three dominant factors: (1) the proximity effect [15], stating that the critical distance between the two enediyne carbon atoms forming the new bond should be in the range of 3.31-3.20 Å for a spontaneous Bergman cyclization at physiological temperature; (2) molecular-strain differences [16,17], leading to a significant activation of some cyclic enediynes; (3) electronic effects [18], influencing the stability of the rearranged enediyne, the transition state, and the biradical that is produced.…”

Synthesis and reactivity of anthracenyl-substituted arenediynes

“…19,20 Thus, we have also varied the size of the ortho substituents (-H, -CH 3 , and -TMS) on the phenyl ring and studied its impact on the conformation of anthracenyl groups and the cyclization reaction. 9-Anthracenylethynyl arenediyne derivatives 1-3, possessing ortho substituents of increasing steric demand -H (1), -CH 3 (2), and -TMS (3) were synthesized (Scheme 2). Compounds 1 and 2 were prepared starting from 9-bromoanthracene (5).…”

“…[1][2][3][4] Single crystals of molecules 1-3 were grown to determine the distance between alkyne groups and the preferred intramolecular orientation of anthracenyl moieties (Fig. 2).…”