Bifunctional Amine‐Squaramides: Powerful Hydrogen‐Bonding Organocatalysts for Asymmetric Domino/Cascade Reactions

Abstract

Organocatalytic domino/cascade reactions provide a convenient method for the construction of complex molecular structures bearing multiple stereocenters in a highly stereoselective fashion. Among various organocatalysts, bifunctional squaramides have emerged as powerful hydrogen‐bonding catalysts for promoting a wide array of useful asymmetric organocascade sequences. Higher activity and ease of preparation make these catalysts excellent alternatives for thiourea‐based organocatalysts. This review highlights the advances in the rapidly growing field of amine‐squaramide‐catalyzed domino/cascade reactions and their mode of action.magnified image

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…[17][18][19][20][21][22][23][24][25][26][27][28][29] However, due to the extremelyf ast growthi no rganocatalyzed domino reactions,m anyn ew developments keep showing up on ad aily basis,w hich makes these reviews somewhat outdated very quickly.I na ddition, many of recentlyp ublished review articles on this topic are quite narrow in terms of theirs cope,f ocusing on either the synthesis of specific scaffolds or the processesm ediated by as pecific type of organocatalyst. [20][21][22][23][24][25][26][27][28][29] Due to the importance of this research and the fast developments in this area, we believe an ew review is needed and, in the present review,w ea re going to summarize the most recent developments in organocatalyzeda symmetric domino reactions,c overing the literature published from the beginning of 2012 up to May,2 017. Althoughs ome of the name reactions,such as the Mannich reactionand Biginelli reaction, are domino in nature,t hey are generally not covered in this review unless they are part of the entire domino reactions,b ecause there are many upto-date reviews out there dedicated to these name reactions.…”

Tunable Bifunctional Phosphine–Squaramide Promoted Morita–Baylis–Hillman Reaction of N‐Alkyl Isatins with Acrylates

“…Lowering the reaction temperature could slightly enhance enantioselectivity (entries3,4and 9i np arenthesis). Moreover, other acrylate esters were also employed in this reaction affording the corresponding products 10 p-r in excellent ees (entries [16][17][18]. It is worth noting that the challenging substrate t-butyl acrylate 9d,w hich was reported to give moderate ee presumably due to the bulky t-butylg roup,g ave 95 % ee in our catalytic system( entry 18).…”

“…As part of our projects in developmento fh ydrogen bond donor chiral squaramide organocatalysts, [15][16] we are interestedi ne xploringt he potential of chiral squaramide organocatalyst [17] in the asymmetric MBH transformation.W ee nvisioned that having the squaramide motif and the highly tunable phosphine moiety within one molecule could synergistically activate the substrates in stereocontrolled manner, which might lead to high enantioselectivity.A ss hown in Figure 2, simplei ncorporation of various substituents into phenyl ring could alter the acidity of the squaramide. [18] Meanwhile,t he diversity of b-aminophosphines could tunet he catalytic activity by steric and electronic effect as well.…”

Weinreb β-Ketoamides in Enantioselective Organocatalysis: A Balance between Reactivity and Selectivity

“…24 We then turned our attention towards squaramide catalysts. 22a, 25 Catalyst D bearing an aromatic substituent on the nitrogen atom of the squaramide moiety performed also poorly (Entry 3), in sharp contrast with those flanked with a benzylic substituent (Entries 4-6). Indeed, the three catalyst E-G delivered the expected product not only with high yields (94-99%) and enantiomeric excesses (95-98% ee), but also excellent diastereomeric ratios (15:1-17:1 dr).…”