Ethyl Isocyanoacetate as a Useful Glycine Equivalent

a-Isocyanoacetates are well-known glycine templates for the synthesis of racemic a,a-disubstituted a-amino acids. [1] However, catalytic enantioselective alkylation of a-isocyanoacetates remains underexploited. Ito, Hayashi, and co-workers pioneered the field by discovering the first palladiumcatalyzed enantioselective allylation of methyl a-phenyl-aisocyanoacetate [Eq. (1), Scheme 1; DBU = 1,8-diazabicyclo-[5.4.0]undec-7-ene]. [2] The enantioselectivity of this reaction was, however, moderate (< 39 % ee). In contrast, a number of Lewis-acid-and small-organomolecule-catalyzed enantioselective [2+3] cycloadditions of a-isocyanoacetates with aldehydes, [3] imines, [4] azodicarboxylates, [5] and polarized carboncarbon double bonds, such as nitroalkenes, [6] a,b-unsaturated ketones, [7] and maleimides, [8] have been developed to access enantioenriched five-membered heterocycles. In contrast, catalytic enantioselective Michael addition of a-isocyanoacetates was met with only limited success. Indeed, it has been established that any Lewis acid catalyzed nucleophilic addition of a-isocyanoacetates to polarized double bonds inevitably provided the [2+3] cycloadducts. The same trend holds true for organocatalytic processes. [8] However, a recent paper from Xu, Wang, and co-workers [9] on a tertiary amine thiourea catalyzed enantioselective Michael addition of aphenyl-a-isocyanoacetate to N-aryl maleimides demonstrated that the aforementioned reaction can be stopped at the Michael adduct stage under appropriate reaction conditions [Eq.(2), Scheme 1].In connection with our ongoing total synthesis project, we needed rapid access to enantiomerically enriched a-aryl-a-(2'-FG-alkyl)-a-amino acids (FG = functional group). [10] We were aware of the seminal contributions of Deng and coworkers on the enantioselective Michael addition of aphenyl-a-cyanoacetate to vinyl phenylsulfone and the subsequent conversion of the enantiomerically enriched adduct into a,a-disubstituted amino acids [Eq. (3), Scheme 1]. [11] However, six steps were needed to convert both the cyano and sulfone groups into other organic residues. Stimulated by

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“…97:3). 1 . Keywords: asymmetric synthesis · heterocycles · natural products · organocatalysis · selenium…”

Section: Methodsmentioning

confidence: 99%

“…[1] However, catalytic enantioselective alkylation of a-isocyanoacetates remains underexploited. Ito, Hayashi, and co-workers pioneered the field by discovering the first palladiumcatalyzed enantioselective allylation of methyl a-phenyl-aisocyanoacetate [Eq.…”

mentioning

confidence: 99%

Catalytic Enantioselective Michael Addition of α‐Aryl‐α‐Isocyanoacetates to Vinyl Selenone: Synthesis of α,α‐Disubstituted α‐Amino Acids and (+)‐ and (−)‐Trigonoliimine A

2013

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“…Later, we have introduced a one-step method to synthesize various 9,10-diarylanthracenes 62 a-f in 2002 by using SM cross-coupling reaction with a variety of boronic acids 61 a-f (Scheme 22). [28] Next, this methodology has been extended to generate various 9,10-diaryl anthracene derivatives starting with the 9,10-dichlorooctafluroanthracene. Around same time, several substituted anthracene derivatives were synthesized and this work was published in 2002, [28] which serve as N-type organic semiconductors and they are useful as electroluminescent devices.…”

Section: Suzuki-miyaura Cross-coupling Reactionmentioning

confidence: 99%

“…To this end, an alternative protocol using a Stille coupling reaction was used to assemble the required 9,10-di(furan-2-yl) anthracene (DFA, 62 e) as a key precursor, assembled by our group. [28] Later, building block 77 was utilized for the synthesis of highly functionalized optical materials such as 2,2'-((5,5'anthracene-9,10-diyl)bis(furan-5,2-diyl))bis(methanylylidene))-dimalononitrile (DCNFA, 79) (Scheme 26).…”

Section: Suzuki-miyaura Cross-coupling Reactionmentioning

confidence: 99%

“…[114] In 1997, various indanebased AAA derivatives have been synthesized from suitable dibromides using ethyl isocyanoacetate (EICA, 222) as a glycine equivalent (Scheme 94). [115] Due to interesting biological properties of quinoxaline system, in 1997, we have demonstrated the synthesis of quinoxaline-containing AAA derivatives (Scheme 95). [116] Later, this strategy has been extended with solid support.…”

Section: α-Amino Acidsmentioning

confidence: 99%

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Development of New Synthetic Strategies, Tactics and their Applications

Kotha

Meshram

2019

The Chemical Record

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This account covers our work related to the development of various synthetic methodologies since 1994. We summarized our strategies and their application to design various functional molecules. In this regard, we also report the utility of our methodologies in others research work. These methods we report here are simple and efficient for the synthesis of a wide variety of intricate molecules such as heterocycles, polycycles, unusual α‐amino acids, star‐shaped molecules, and modified peptides. For this purpose, we used various transition metal‐based reagents and catalysts. Various popular reactions such as metathesis, Suzuki coupling, [2+2+2] cyclotrimerization were used to assemble these targets. Moreover, rongalite has been used to expand the Diels‐Alder chemistry.

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Bucherer–Bergs and Strecker Multicomponent Reactions

Marqués‐López¹,

Herrera²

2015

Multicomponent Reactions

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Ethyl Isocyanoacetate as a Useful Glycine Equivalent

Cited by 61 publications

References 35 publications

Catalytic Enantioselective Michael Addition of α‐Aryl‐α‐Isocyanoacetates to Vinyl Selenone: Synthesis of α,α‐Disubstituted α‐Amino Acids and (+)‐ and (−)‐Trigonoliimine A

Catalytic Enantioselective Michael Addition of α‐Aryl‐α‐Isocyanoacetates to Vinyl Selenone: Synthesis of α,α‐Disubstituted α‐Amino Acids and (+)‐ and (−)‐Trigonoliimine A

Development of New Synthetic Strategies, Tactics and their Applications

Bucherer–Bergs and Strecker Multicomponent Reactions

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