Catalytic Asymmetric [4 + 2] Cycloadditions of Ketenes and <i>N</i>-Thioacyl Imines:  Alternatives for Direct Mannich Reactions of Enolizable Imines

In the field of catalytic, asymmetric synthesis, there is a growing emphasis on multifunctional systems, in which multiple parts of a catalyst or multiple catalysts work together to promote a specific reaction. These efforts, in part, are result-driven, and they are also part of a movement toward emulating the efficiency and selectivity of nature's catalysts, enzymes. In this Account, we illustrate the importance of bifunctional catalytic methods, focusing on the cooperative action of Lewis acidic and Lewis basic catalysts by the simultaneous activation of both electrophilic and nucleophilic reaction partners. For our part, we have contributed three separate bifunctional methods that combine achiral Lewis acids with chiral cinchona alkaloid nucleophiles, for example, benzoylquinine (BQ), to catalyze highly enantioselective cycloaddition reactions between ketene enolates and various electrophiles. Each method requires a distinct Lewis acid to coordinate and activate the electrophile, which in turn increases the reaction rates and yields, without any detectable influence on the outstanding enantioselectivities inherent to these reactions. To place our results in perspective, many important contributions to this emerging field are highlighted and our own reports are chronicled. PAULL et al.

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“…This system affords the [4 + 2] cycloadducts in high yield with excellent stereochemical control. 32 …”

Section: Other Noteworthy Systemsmentioning

confidence: 99%

Bifunctional Asymmetric Catalysis: Cooperative Lewis Acid/Base Systems

et al. 2008

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“…Nelson and co-workers reported cinchona alkaloid-catalyzed [4 + 2] cycloaddition of ketenes and N-thioacyl imine, affording the 4,5-cis-disubstituted 1,3-thiazin-6-one derivatives 146 with high enantioselectivities (³95% ee) and diastereoselectivities (³95:5 cis:trans), Scheme 3.47 [63]. Ketene, in situ generated from acyl halide 143 and base, followed by addition to imine which was generated in situ via basic elimination of a-amido sulfone 144, providing the ketene-imine addition pathway toward the cycloadducts.…”

Section: Scheme 345 Bisoxazoline-catalyzed Diels-alder Reactionmentioning

confidence: 99%

Organocatalyzed Cycloadditions

Hong¹

2011

Enantioselective Organocatalyzed Reactions II

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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...

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“…In a preliminary study, it was found that some unidentified byproducts as well as the desired quinoxalinone were formed, which made the reaction sluggish and resulted With Zn(OTf) 2 (10 mol%) as the cocatalyst, the 3,4-dihydroquinoxalin-2-one products 4 were obtained in remarkably increased yields and with excellent enantioselectivities (>99% ee) in each case (Table 10.1, entries [1][2][3][4][5][6][7][8][9][10][11][12]. It is worth to note that the opposite enantiomer was obtained with similarly high enantioselectivity and yield for the cycloaddition reaction when benzoylquinine (BQN, 1b) was used instead of BQD 1a (entry 13).…”

Section: Asymmetric Cycloadditions Catalyzed By Quinuclidine Tertiarymentioning

confidence: 99%

“…It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkylsubstituted ketenes and aliphatic imine electrophiles (!95% ee, !95% cis : trans) [12].…”

Section: Asymmetric Cycloadditions Catalyzed By Quinuclidine Tertiarymentioning

confidence: 99%

Cinchona‐Catalyzed Cycloaddition Reactions

Liu

Chen

2009

Cinchona Alkaloids in Synthesis and Catalysis

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Asymmetric pericyclic reaction represents one of the most straightforward protocols to access enantioenriched cyclic compounds and triggers continuing interest in organic synthesis. Fruitful results have been achieved by the catalysis of chiral metal complexes over the past decades [1]. On the other hand, recently small organic molecules have also contributed a lot to this area owing to the rapid development of asymmetric organocatalysis [2].Cinchona alkaloids are readily available natural chiral compounds and have a long history to be utilized as organocatalysts in asymmetric catalysis [3,4]. They are multifunctional, tunable, and more importantly, they could promote a diversity of reactions through different catalytic mechanisms, which make them privileged catalysts in organocatalysis. In this chapter, the applications of cinchona alkaloids and their derivatives for asymmetric cycloaddition reactions after 2000, especially for the construction of a variety of five-and six-membered cyclic compounds, are discussed. Asymmetric Cycloadditions Catalyzed by Quinuclidine Tertiary AmineCinchona alkaloids possess a nucleophilic quinuclidine structure and can perform as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an acid scavenger. The resulting ketene enolates can react with electrophilic C¼O or C¼N bonds to deliver chiral b-lactones [5] or b-lactams [6], respectively, in a [2 þ 2] cycloaddition manner, which is discussed in Chapter 5 in detail. Gaunt et al. also developed practical one pot cyclopropanation processes mediated by the modified cinchona alkaloids via ammonium ylide intermediates [7]. Although the catalytic strategy has been well established, the utilization of ammonium enolate based [4 þ 2] cycloaddition is rare probably because of the relative unreactivity of the Cinchona Alkaloids in Synthesis and Catalysis, Ligands, Immobilization and Organocatalysis Edited by Choong Eui Song

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Catalytic Asymmetric [4 + 2] Cycloadditions of Ketenes and N-Thioacyl Imines: Alternatives for Direct Mannich Reactions of Enolizable Imines

Cited by 63 publications

References 11 publications

Bifunctional Asymmetric Catalysis: Cooperative Lewis Acid/Base Systems

Bifunctional Asymmetric Catalysis: Cooperative Lewis Acid/Base Systems

Organocatalyzed Cycloadditions

Cinchona‐Catalyzed Cycloaddition Reactions

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