Diazo Compounds: Versatile Synthons for the Synthesis of Nitrogen Heterocycles <i>via</i> Transition Metal‐Catalyzed Cascade C–H Activation/Carbene Insertion/Annulation Reactions

Xiang, Yunyu; Wang, Cong; Ding, Qiuping; Peng, Yiyuan

doi:10.1002/adsc.201800960

Cited by 205 publications

(66 citation statements)

References 151 publications

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“…32 Additionally, when treated with the appropriate transition metal, diazo compounds form amphiphilic metallocarbene reagents 26 capable of a wide range of transformations including cyclopropanations, C-H insertions, and 1,3-dipolar cycloadditions (Scheme 11a). 33,34 Of these transformations, cyclopropanations are of great interest due to their prevalence in pharmaceuticals, biologically relevant molecules, as well as reagents for organic synthesis. 35,36 The thermal ring expansion of vinyl cyclopropanes 27 is a powerful strategy for the formation of five-membered carbocycles 28, however, the high temperatures (500-600 °C) in addition to the tentative diradical intermediate 29 limit the efficacy of rendering the rearrangement stereo-and/or chemoselective (Scheme 11b).…”

Section: (4+1)-cyclizations Employing a Cyclopropanation/ring-expansion Sequencementioning

confidence: 99%

(4+1)-Cycloadditions Exploiting the Biphilicity of Oxyphosphonium Enolates and RhII/PdII-Stabilized Metallocarbenes for the Construction of Five-Membered Frameworks

Tucker¹,

Ashfeld²

2021

Synlett

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Abstract(4+1)-Cyclizations are an underutilized disconnect for the formation of five-membered heterocyclic and carbocyclic frameworks. Herein we analyze methods employing oxyphosphonium enolates and RhII/PdII-metallocarbenes as C1 synthons in the presence of several four-atom components for the synthesis of 2,3-dihydrobenzofurans, 2,3-dihydroindoles, oxazolones, cyclopentenones, and pyrrolones.1 Introduction2 (4+1)-Cyclizations Employing Kukhtin–Ramirez-Like Reactivity3 (4+1)-Cyclizations Employing a Cyclopropanation/Ring-Expansion Sequence4 Pd-Catalyzed (4+1)-Cyclizations through Carbene Migratory Insertion/Reductive Elimination Processes5 Summary

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Section: (4+1)-cyclizations Employing a Cyclopropanation/ring-expansion Sequencementioning

confidence: 99%

(4+1)-Cycloadditions Exploiting the Biphilicity of Oxyphosphonium Enolates and RhII/PdII-Stabilized Metallocarbenes for the Construction of Five-Membered Frameworks

Tucker¹,

Ashfeld²

2021

Synlett

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“…Therefore, a representative group of in-house made Escherichia coli overexpressed ADHs was evaluated ( Table 2), including the enzymes from Rhodococcus ruber (ADH-A) [38], Thermoanaerobium species (ADH-T) [39], Lactobacillus brevis (LB-ADH) [40,41], Ralstonia species (Ras-ADH) [42,43], Sphingobium yanoikuyae (Sy-ADH), [44,45], and Thermoanaerobacter ethanolicus (Tes-ADH) [46]. Unfortunately, poor activities (<10% conversion, entries [1][2][3][4][5][6] were observed for all these E. coli overexpressed ADHs, except for the Ras-ADH, which led to the formation of a complex mixture of unidentified products [47]. Next, diazo keto esters 2a-i were chemically reduced by employing sodium borohydride (NaBH 4 ) in tetrahydrofuran (THF) as the solvent at 0 • C for only 10 min to give the expected α-diazo-β-hydroxy esters 3a-i in moderate to high yields after column chromatography purification (62-85%, Table 1).…”

Section: Bioreduction Of Ethyl 4-azido-2-diazo-3-oxobutanoate (2a)mentioning

confidence: 99%

“…α-Diazo carbonyl compounds are widely recognized as versatile reagents in organic synthesis and chemical biology [1][2][3][4][5]. The chemistry of α-diazo-β-hydroxy carbonyl compounds attracts particular attention, as these functionalized compounds have been employed in the synthesis of amino acid analogues and heterocycles of biological relevance [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Bioreduction of α-diazo-β-keto Esters

et al. 2020

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Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living systems. Much effort has been made in recent years to explore their accessibility and synthetic potential; however, their preparation through stereoselective enzymatic asymmetric synthesis has been scarcely reported in the literature. Alcohol dehydrogenases (ADHs, also called ketoreductases, KREDs) are powerful redox enzymes able to reduce carbonyl compounds in a highly stereoselective manner. Herein, we have developed the synthesis and subsequent bioreduction of nine α-diazo-β-keto esters to give optically active α-diazo-β-hydroxy esters with potential applications as chiral building blocks in chemical synthesis. Therefore, the syntheses of prochiral α-diazo-β-keto esters bearing different substitution patterns at the adjacent position of the ketone group (N3CH2, ClCH2, BrCH2, CH3OCH2, NCSCH2, CH3, and Ph) and in the alkoxy portion of the ester functionality (Me, Et, and Bn), were carried out through the diazo transfer reaction to the corresponding β-keto esters in good to excellent yields (81–96%). After performing the chemical reduction of α-diazo-β-keto esters with sodium borohydride and developing robust analytical conditions to monitor the biotransformations, their bioreductions were exhaustively studied using in-house made Escherichia coli overexpressed and commercially available KREDs. Remarkably, the corresponding α-diazo-β-hydroxy esters were obtained in moderate to excellent conversions (60 to >99%) and high selectivities (85 to >99% ee) after 24 h at 30 °C. The best biotransformations in terms of conversion and enantiomeric excess were successfully scaled up to give the expected chiral alcohols with almost the same activity and selectivity values observed in the enzyme screening experiments.

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“…In this context, a number of transition‐metals such as Fe, Cu, Pd, Pt, Ni, Rh, Ru, Ag, Au etc. have been used for generating metal‐carbene complex through the decomposition of diazo compounds or their equivalents to develop novel synthetic methodologies or to synthesize natural products and pharmaceutical molecules [7] . However, the low abundance and high cost of some of the transition metals e. g. Rh, Pd, Ru, Ir etc.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Iron‐Catalyzed Chemical and Enzymatic Carbene‐Transfer Reactions

Kaur

Tyagi

2021

Adv Synth Catal

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The use of diazo compounds in the transition‐metal‐catalyzed coupling reactions to form C−C and C−X (X=O, S, N, Si, P etc.) bonds have been a well established approach in organic synthesis. In this context, various transition metals such as Pd, Cu, Rh, Ni, Co, Fe, Ir etc. have proved useful to generate a metal‐carbene intermediate which subsequently undergoes carbene transfer or insertion to form C−C, C−Si or C‐heteroatom bonds. However, the use of most abundant, cheaper and environmentally benign metal such as iron to catalyze carbene‐transfer reactions has attracted considerable attention in the last few years. Iron is the second most abundant transition metal in nature and also an integral part of various biological systems which make it highly valuable to use as a catalyst in organic chemistry. This review summarizes the efforts made after 2013 in the area of iron‐catalyzed chemical and enzymatic carbene‐transfer reactions using diazo compounds as carbene precursor.

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Diazo Compounds: Versatile Synthons for the Synthesis of Nitrogen Heterocycles via Transition Metal‐Catalyzed Cascade C–H Activation/Carbene Insertion/Annulation Reactions

Cited by 205 publications

References 151 publications

(4+1)-Cycloadditions Exploiting the Biphilicity of Oxyphosphonium Enolates and RhII/PdII-Stabilized Metallocarbenes for the Construction of Five-Membered Frameworks

(4+1)-Cycloadditions Exploiting the Biphilicity of Oxyphosphonium Enolates and RhII/PdII-Stabilized Metallocarbenes for the Construction of Five-Membered Frameworks

Stereoselective Bioreduction of α-diazo-β-keto Esters

Recent Advances in Iron‐Catalyzed Chemical and Enzymatic Carbene‐Transfer Reactions

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