Organocatalyzed Cycloadditions

Abstract

Cycloadditions have been for a long time one of the most useful reactions in organic synthesis. Recently, the ability to promote the reactions by organocatalysts further expands the realm of its synthetic application. This review aims to highlight the recent advances in this area with particular emphasis on the asymmetric cycloaddition promoted by organocatalysts. IntroductionGenerating selectively the maximum number of bonds and stereogenic centers in a one-step (or one-pot) reaction constitute to be of key interest in synthetic chemistry. Among many methodologies for the objective, cycloaddition stand out. While searching for a better and tunable catalyst able to promote a wide spectrum of cycloaddition, organocatalysis was revealed as a powerful tool for efficient operations and many other merits, e.g., high stereoselectivity, moisture and air resistant, environmental benign and user friendly. Surprisingly, organocatalytic synthesis was virtually dominant for few decades until just the turn of this century [1]; nevertheless, it soon become the focal point, and it has occupied an important chapter in the modern synthetic chemistry [2]. In a very short period of time, more than hundred review articles of organocatalytic reactions were reported, and the papers are continuing to appear for summarizing up the thriving and robust subject. Several theoretical studies, including the computational Intramolecular CycloadditionsIn 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,b-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malimide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan's conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation), Scheme 3.2 [7]. In 2003, an interesting intramolecular organocatalytic [3 + 2] dipolar cycloaddition of an enynoate (19) catalyzed by PBu 3 was developed by Krische and his coworker in the total synthesis of (±)-hirsutene (21), Scheme 3.6 [12]. The intramolecular phosphane-catalyzed [3 + 2] dipolar cycloaddition provides a concise approach to the linear triquinane hirsutene, whereby three contiguous stereogenic centers are created and controlled in a single reaction step.A light-driven enantioselective organocatalysis intramolecular [2 + 2] photocycloaddition of quinolone (24) [4 + 2] cycloadditions. The enantioselectivity was rationalized by the fact that selective formation of the (E)-iminium isomer to avoid nonbonding interactions between the substrate olefin and the geminal methyl substituents and the benzyl group on the catalyst framework which effectively shields the re face of the dienophile, leaving the si face exposed to cycloadditio...

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D2 and (−)- and (+)-Microminutinin

“…In this context and in efforts to expand our interest in asymmetric organocatalytic annulations with cascade reactions and one-pot operations, we conceived a scenario in which an organocatalytic Michael–acetalization of nitroalkene ( 2 ) and aldehyde ( 3 ) followed by reduction and a Nef reaction sequence would provide an efficient platform for the construction of the functionalized aflatoxin system (Scheme ).…”

Organocatalytic Enantioselective Michael–Michael–Henry Reaction Cascade. An Entry to Highly Functionalized Hajos–Parrish-Type Ketones with Five to Six Contiguous Stereogenic Centers and Two Quaternary Carbons

“…Consequently, such an asymmetric catalytic cascade reaction for the synthesis of highly functionalized HPK analogues is unprecedented and is a compelling subject of investigation. In the context of this background and in an effort to extend our interest in multicomponent organocatalytic asymmetric annulations with cascade reactions or one-pot operations, we envisaged that a double Michael–Henry cascade of organocatalytic reactions of 2-alkylcyclopentane-1,3-dione ( 1 ), α,β-unsaturated aldehyde ( 2 ), and nitroalkene ( 3 ) might provide an appropriate protocol for the construction of highly functionalized HPK ( 4 ) containing six contiguous stereogenic centers (Scheme ). While the idea is straightforward and the preceding intramolecular HPESW reaction has been demonstrated in many variants, and even though the cascade intermolecular reaction with cyclopentane-1,3-dione remains elusive, other factors may impede the development of such a reaction sequence.…”

One-Pot Dichotomous Construction of Inside-Azayohimban and Pro-Azayohimban Systems via an Enantioselective Organocatalytic Cascade; Their Use as a Model to Probe the (Aza-)Indole Local Solvent Environment

“…In this proof-of-concept study, 7-azaindole instead of 2,7-diazaindole (or (2,7-aza)­Trp) was selected to avoid the reaction complexity (vide infra). We then strategically designed and synthesized a series of 7-diazaindole derivatives using organocatalytic Michael/Michael/Pictet–Spengler-lactamization as the key step , (Scheme ). To our surprise, with only subtle differences between 7-azaindole and indole, i.e., the N(7) versus C(7), the cascade reaction led to a very distinct outcome.…”