The first organocatalytic, ortho-regioselective inverse-electron-demand hetero-Diels–Alder reaction

Abstract

The development of the unprecedented ortho-regioselective inverse-electron-demand hetero-Diels-Alder (IEDHDA) reaction is described. It has been demonstrated that by proper choice of reactants and reaction conditions the inverse-electron-demand hetero-Diels-Alder cycloaddition can be realized with unprecedented regioselectivity arising from the reaction between the terminal carbon atom of the dienophile and the heteroatom of the heterodiene.

The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

“…The observed results of these reactions collected in Table 1 clearly demonstrate that the proportions of cycloadducts 11 and 14 formed under standard conditions reflect to some extent the composition of the "thiochalcone fraction". Introduction of an electron-donating group at the Ar 1 substituent (j, k, and l) in thiochalcone 1 (entries [13][14][15] or previous equilibration of "thiochalcone fractions" in CH 2 Cl 2 (entries 3 and 5) increases the content of the endo-4 dimer in the mixture, and hence, favors the formation of bis-heterocyclic products of type 14/14'. To the best of our knowledge, these are the first examples of [4+2]-cycloadditions of an electron-deficient heterodiene with dimeric thiochalcones of type 4 playing the role of the electron-rich C=S heterodienophile.…”

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

“…Despite the fact that thiochalcones exist in solution as mixtures of dimers [15–16], they enter into cycloaddition reactions not only as heterodienes [17–19], but also as heterodipolarophiles [15]. In two recent publications we reported new thia-Diels–Alder reactions of aryl, hetaryl and ferrocenyl-substituted thiochalcones with acetylenic dienophiles, which lead to the corresponding 4 H -thiopyrans in a regioselective manner [16,20].…”

Intramolecular [2+2]‐Cycloaddition in the Synthesis of Polycyclic Tetrahydrothiopyran Derivatives Bearing a Cyclobutane Scaffold

“…[7] Recently, we have developed a new strategy for the synthesis of dihydrothiopyrans 4 based on the inverseelectron-demand hetero-Diels-Alder reaction between dienamines [8] generated in situ form enals 1 under aminocatalytic conditions and thiochalcones 2 (Scheme 2, top). [9] This [4 + 2]-cycloaddition proceeded with unprecedented ortho-regioselectivity enabling access to interesting dihydrothiopyrans 4 with a unique substitution pattern. Taking advantage of the developed method, we envisioned that the substitution pattern present in 4 is suitable for the construction of cyclobutane framework incorporated into a complex and very interesting polycyclic architecture (Scheme 2, bottom).…”

“…However, we had to follow scope and limitations of the method according to our previous studies. [9] Therefore, dihydrothiopyrans 4 a-c bearing either electronpoor or electron-rich aromatic rings at the 3 position were synthesized by changing the structure of starting aldehydes 1. Similarly, the substitution pattern at the C-4 position of dihydrothiopyrans 4 d-f was readily modified by performing the [4 + 2]-cycloaddition with thiochalcones 2 bearing different aromatic groups in the β-position.…”