Carbon Dioxide-Catalyzed Stereoselective Cyanation Reaction

Roy, Tamal; Kim, Myungjo J.; Yang, Yang; Kim, Su Yeon; Kang, Gyumin; Ren, Xinyi; Kadziola, Anders; Lee, Hee‐Yoon; Baik, Mu‐Hyun; Lee, Jiwoong

doi:10.1021/acscatal.9b01087

Cited by 26 publications

(16 citation statements)

References 32 publications

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“…However, it is important to note that the employment of CO 2 can complicate the outcome of reactions due to undesired binding of nucleophiles therefore reducing the reactivity. Based on our investigation and previous studies [15,27,28], we presumed that the positive effects of CO 2 in catalyzing chemical reactions can be general, particularly in reactions involving reversible steps. In the current investigation with chalcones, the reaction is highly controlled by thermodynamics that allowed us to access various products in high yield.…”

Section: Discussionmentioning

confidence: 72%

“…The use of solid metal cyanide sources is desirable to avoid volatile HCN, however, it often requires high reaction temperature due to the low solubility and reactivity of alkali metal cyanides [14]. Recently our group demonstrated the employment of catalytic amounts of CO 2 for 1,4-conjugate cyanide addition reaction of coumarin substrates [15]. The use of ammonium cyanide as a nucleophile was sufficient to quantitatively convert the starting materials to the desired products under 1 atm of CO 2 (Scheme 1A).…”

Section: Introductionmentioning

confidence: 99%

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A CO2-Mediated Conjugate Cyanide Addition to Chalcones

et al. 2020

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Carbon dioxide is an intrinsically stable molecule; however, it can readily react with various nucleophilic reagents. In the presence of a cyanide source, CO2 was proven to be useful to promote addition reactions. Here we report the use of CO2 to facilitate 1,4-conjugate cyanide addition reaction to chalcones to generate organonitriles. Nitriles are key component in organic synthesis due to their utility in numerous functional group transformation, however, conjugation addition of cyanide has been a challenge in this substrate class due to side reactions. To mitigate this, we employed simple ammonium and metal cyanide sources as nucleophiles under carbon dioxide atmosphere where high selectivity toward the desired product was obtained. The presented reaction is not feasible under inert atmosphere, which highlights the important role of CO2, as a Lewis and Brøndsted acidic catalyst. Further derivatization of organonitriles compounds were performed to showcase the utility of the reaction, while an unprecedented dimerization reaction was identified and characterized, affording a cyclopentanone scaffold.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

A CO2-Mediated Conjugate Cyanide Addition to Chalcones

et al. 2020

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“…Recent applications of carbon dioxide in organic synthesis showed fruitful success particularly in CO 2 ‐incorporation, [5] CO 2 as a temporal protecting group for C−H activation, [6] CO 2 for asymmetric catalysis [7] and oxidation reactions [8] . We recently investigated the role of CO 2 in a cyanation reaction, [9] where CO 2 can be used in catalytic amounts to facilitate the stereoselective transformation of activated electrophiles via 1,4‐conjugate addition reactions. Cyanohydrin synthesis −1,2‐cyanide addition reactions to carbonyls—is one of the oldest C−C bond‐forming reactions using HCN as a cyanide source [10] .…”

Section: Methodsmentioning

confidence: 99%

CO₂‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

Juhl

Petersen

Lee

2020

Chemistry A European J

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Thermodynamic andk inetic control of ac hemical process is the key to access desired products and states. Changes are made when ad esired product is not accessible;o ne may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere,t he reaction is essentially not operative due to the unfavored equilibrium. The utilityo f CO 2-mediated selective cyanohydrins ynthesis was further showcased by broadening Kiliani-Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl-a nd arylaldehydes, KCN and an atmospheric pressureo fC O 2. Achemical reaction is governed by kinetics and thermodynamics, and as imultaneous controlo fb oth parameters is a commonp ractice in designing and optimizing chemical reactions. The manipulation of thermodynamic stability of reactants and products will decide the outcome of ac hemical process, while variousr eactionp athways can lead to undesired products thus reducing overall efficiency of the process. [1] To circumvent unwanted reactionp athways, chemists have developed selectivec atalysis,p rotecting groups ("P" in Scheme1), trappingr eagents and reactivity-altered reactants (A' and B'), which in turn can limit the scopea nd generality of the original reaction. In our ongoing pursuit to implement CO 2 in the core of organic synthesis, we sought out ways in which equilibria can be controlled by the use of CO 2-a mild Lewis acid where anionic intermediates can be stabilized. Carbon dioxide is an intrinsicallys table molecule, [2, 3] however,i tc an readily and reversibly react with various nucleophiles. [2, 4] Recent applicationso fc arbond ioxide in organic synthesis showed fruitful successp articularly in CO 2-incorporation , [5] CO 2 as at emporal protecting group for CÀHa ctivation, [6] CO 2 for asymmetricc atalysis [7] and oxidation reactions. [8] We recently investigated the role of CO 2 in ac yanation reaction, [9] where CO 2 can be used in catalytic amountst of acilitate the stereoselective transformation of activated electrophiles via 1,4-conjugate addition reactions. Cyanohydrin synthesis À1,2-cyanide addition reactions to carbonyls-is one of the oldestC ÀCb ond-forming reactions using HCN as ac yanide source. [10] Despite the high utility of cyanohydrins in organic synthesis [11-14] the use of HCN reduces its application potential due to its volatile nature and health risks. Recent research activitiesi nc yanohydrin synthesis are mainly performed by using TMSCN 15] and cyanoformate [16] as aH CN surrogate. [11, 12, 17] These reagents suffer from poor atom economyw hen unprotected cyanohydrins are desired. Furthermore,t he cyanation reactions with in situ generated HCN (from am ixture of TMSCNa nd an alcohol) are limitedb yt he instability of the cyani...

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“…Although NaBH(OCHO) 3 is a congener of NaBH(OAc) 3 , the use of NaBH(OCHO) 3 as a reducing agent for reductive amination has to the best of our knowledge not yet been reported. Our on‐going research program to utilize CO 2 for controlling organic reactions [ 17 ] showed promising reactivity patterns in developing new chemical reactivity of nucleophiles while improving (stereo)selectivity. Although, the reactivity and selectivity of NaBH 4 can conveniently be modified through the addition of reagents or Lewis acidic metals to NaBH 4 , CO 2 has been overlooked for this purpose.…”

Section: Introductionmentioning

confidence: 99%

CO₂‐Controlled Reductive Amination Reactions with NaBH₄

2020

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We report the use of CO2 to curb the reactivity of NaBH4 enabling its use in reductive amination reactions. CO2 readily reacts with NaBH4 to decrease its capacity to reduce aldehydes to alcohols while remaining able to reduce imines and iminium ions for desired alkylation reactions. The formation of NaBH(OCHO)3 as a reducing reagent was critical to achieve the desired selectivity. A general protocol was established for C–N bond formation reactions and replacing NaBH4 with NaBD4 allowed for reductive amination with concomitant deuteration to be carried out.

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Carbon Dioxide-Catalyzed Stereoselective Cyanation Reaction

Cited by 26 publications

References 32 publications

A CO2-Mediated Conjugate Cyanide Addition to Chalcones

A CO2-Mediated Conjugate Cyanide Addition to Chalcones

CO₂‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

CO₂‐Controlled Reductive Amination Reactions with NaBH₄

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Carbon Dioxide-Catalyzed Stereoselective Cyanation Reaction

Cited by 26 publications

References 32 publications

A CO2-Mediated Conjugate Cyanide Addition to Chalcones

A CO2-Mediated Conjugate Cyanide Addition to Chalcones

CO2‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

CO2‐Controlled Reductive Amination Reactions with NaBH4

Contact Info

Product

Resources

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CO₂‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

CO₂‐Controlled Reductive Amination Reactions with NaBH₄