Bifunctional Hydrogen‐Bond Donors That Bear a Quinazoline or Benzothiadiazine Skeleton for Asymmetric Organocatalysis

Abstract

Hydrogen-bond (HB)-donor catalysts that bear a 2-aminoquinazolin-4-(1H)-one or a 3-aminobenzothiadiazine-1,1-dioxide skeleton have been developed, and it has been shown that these catalyst motifs act similarly to other HB-donor catalysts such as thioureas. The highly enantioselective hydrazination of 1,3-dicarbonyl compounds was realized even at room temperature with up to 96% ee for 2-aminoquinazolin-4-(1H)-one-type catalysts, which were more effective than the corresponding urea and thiourea catalysts. In addition, benzothiadiazine-1,1-dioxide-type catalysts were shown to promote the isomerization of alkynoates to allenoates with high enantioselectivity. To overcome the problem that the products were obtained as mixtures with the starting alkynoates, we developed the tandem isomerization and cycloaddition of alkynoates for the synthesis of advanced chiral compounds such as bicyclo[2.2.1]heptenes and 3-alkylidene pyrrolidine without a significant loss of enantioselectivity.

Bifunctional Guanidines as Hydrogen-Bond-Donating Catalysts

“…Therefore, there have been so far many reports on the asymmetric synthesis of optically active allenes [27,28]. Among them, we focused on the base-catalyzed isomerization of alkynylesters into allenoesters from the atom-economical perspective [8,9,[29][30][31]. …”

“…Under these conditions, the association constants of thiourea 1a, quinazoline 2a, and benzothiadiazine 3a were estimated to be 1.2 Â 10 3 (AE37), 4.9 Â 10 2 (AE18), and 1.9 Â 10 3 (AE44), respectively. Therefore, the relative abilities of these HB donors to associate with Lewis bases were remarkably different and followed the order 3a > 1a > 2a [8].…”

“…To avoid this problem, we designed new hydrogen-bond donors bearing cyclic guanidine motifs, in which the thiourea moiety and the aryl group of the catalyst 1a are linked as shown in Fig. 1 [8]. Furthermore, the acidities of two N-H protons of the guanidines can be enhanced by choosing a suitable tether (C¼O or SO 2 ) as well as a substituent (R ¼ F, CF 3 , etc.)…”

“…In this chapter, the asymmetric reactions using bifunctional guanidine catalysts as well as the chemical structure and design concept of these catalysts are described [8][9][10][11][12].…”

Diastereo- and Enantioselective [4+2] Cycloadditions of Cyclic Enones with Cyclic 1-Azadienes

“…与我们前面已报道的研究类 似 [4] , 采用含 OH 官能团的手性伯胺 C4 时 [9] , 同样可实 现非对映选择性的反转, 主要生成 exo-环加成产物 3a'(Entry 3). 我们进一步筛选了一系列含各种氢键供体 的双功能伯胺催化剂 [10] C5～C8 (Entries 4～7), 发现都 能够提高 endo-选择性, 特别是采用含苯并噻二嗪类结 构的催化剂 C8 [11] 果(Entries 11～13), 甚至包括烷基取代的 1-氮杂二烯 (Entry 14). 我们还进一步研究了含磺酸酯基的 1-氮杂二 烯底物 4 [12] , 也能顺利生成 endo-选择性的环加成产物, 但对映选择性有所下降(Entries 15 and 16).…”