The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Jason E Camp - One of the best experts on this subject based on the ideXlab platform.
-
A one-pot synthesis of a-formyl-a-allylacetates via Nucleophilic Catalysis
2020Co-Authors: William Chung, Petra Lindovska, Jason E CampAbstract:abstract A step-economical one-pot Nucleophilic Catalysis/thermal Claisen-rearrangement protocol for the directsynthesis of a -formyl- a -allylacetates from allylic alcohols and activated alkynes has been developed. Theproduct a -formyl- -allylacetates were further reacted in situ to give either protected enol ethers or b-hydroxy-4-pentenoates. 2011 Elsevier Ltd. All rights reserved. a -Formyl- a -allylacetates are found in a number of biologicallyactivenaturalproducts 1 andareimportantintermediatesinthesyn-thesis of peptide inhibitors, 2 as well as biologically active uracils 3 and pyrimidines. 4 These compounds are challenging substrates tosynthesize via conventional enolate chemistry due to their propen-sity to undergo dimerization reactions and multiple allylations. 5,6 The most common method for a -formyl- a -allylacetate formationis via formylation of a c ,d-unsaturated ester, 2 which itself must besynthesized. Thus, a more step-economical methodto these impor-tant compounds from commercial starting materials would behighly beneficial. A one-pot synthesis would be an ideal approachas it minimizes the transfer of material and avoids the purificationsteps.
-
synthesis of 2 4 disubstituted imidazoles via Nucleophilic Catalysis
Synlett, 2020Co-Authors: Dmitrii A Shabalin, Simbarashe Ngwerume, Jason E Camp, Jay J Dunsford, Alexandra Rose Saunders, Duncan M GillAbstract:A convergent, microwave-assisted protocol for the synthesis of disubstituted NH-imidazoles via Nucleophilic Catalysis is described. The substituted imidazoles are accessed via the intramolecular addition of a variety of amidoxime substrates to activated alkynes followed by a thermally induced rearrangement of the in situ generated O-vinylamidoxime species. The unprotected imidazoles contain an aryl group at the 2-position as well as an ester moiety at the 4-position.
-
a one pot synthesis of α formyl α allylacetates via Nucleophilic Catalysis
Tetrahedron Letters, 2011Co-Authors: William Chung, Petra Lindovska, Jason E CampAbstract:Abstract A step-economical one-pot Nucleophilic Catalysis/thermal Claisen-rearrangement protocol for the direct synthesis of α-formyl-α-allylacetates from allylic alcohols and activated alkynes has been developed. The product α-formyl-α-allylacetates were further reacted in situ to give either protected enol ethers or β-hydroxy-4-pentenoates.
-
A one-pot synthesis of α-formyl-α-allylacetates via Nucleophilic Catalysis.
2011Co-Authors: William Chung, Petra Lindovska, Jason E CampAbstract:A step-economical one-pot Nucleophilic Catalysis/thermal Claisen rearrangement protocol for the direct synthesis of I±-formyl-I±-allylacetates from allylic alcs. and activated alkynes has been developed. The product I±-formyl-I±-allylacetates were further reacted in situ to give either protected enol ethers or I²-hydroxy-4-pentenoates. [on SciFinder(R)]
-
synthesis of highly substituted pyrroles via Nucleophilic Catalysis
ChemInform, 2011Co-Authors: Simbarashe Ngwerume, Jason E CampAbstract:The procedure renders possible a convenient and regioselective access to 2,4-disubstituted, 2,3,5-trisubstituted and tetrasubstituted pyrrole structures as interesting pharmaceutical scaffolds.
Alexei V Demchenko - One of the best experts on this subject based on the ideXlab platform.
-
regenerative glycosylation under Nucleophilic Catalysis
ChemInform, 2014Co-Authors: Swati S Nigudkar, Keith J Stine, Alexei V DemchenkoAbstract:Glycosylation in the presence of difluorooxindole proceeds in a regenerative manner, allowing to use only catalytic amounts of this activator.
-
regenerative glycosylation under Nucleophilic Catalysis
Journal of the American Chemical Society, 2014Co-Authors: Swati S Nigudkar, Keith J Stine, Alexei V DemchenkoAbstract:This article describes 3,3-difluoroxindole (HOFox)-mediated glycosylation. The uniqueness of this approach is that both the in situ synthesis of 3,3-difluoro-3H-indol-2-yl (OFox) glycosyl donors and activation thereof can be conducted in a regenerative fashion as is a typical reaction performed under Nucleophilic Catalysis. Only a catalytic amount of the OFox imidate donor and a Lewis acid activator are present in the reaction medium. The OFox imidate donor is constantly regenerated upon its consumption until glycosyl acceptor has reacted.
Gregory C Fu - One of the best experts on this subject based on the ideXlab platform.
-
enantioselective Nucleophilic Catalysis the synthesis of aza β lactams through 2 2 cycloadditions of ketenes with azo compounds
Angewandte Chemie, 2008Co-Authors: Jacob M Berlin, Gregory C FuAbstract:Although aza-β-lactams have attracted interest due to their biological activity[1] and to their utility as intermediates in organic chemistry (e.g., for the generation of α-amino acids[2] and of hydantoins[3]),[4] only limited progress has been described with regard to the enantioselective synthesis of this family of heterocycles.[5] One attractive, convergent approach to the formation of aza-β-lactams is the [2+2] cycloaddition of a ketene with an azo compound [Eq. (1)].[6] To the best of our knowledge, no stereoselective variants of this process have yet been reported. (1) We have been exploring the use of chiral derivatives of PPY (PPY = 4-(pyrrolidino)pyridine; e.g., 1 and 2) as enantioselective catalysts for an array of transformations,[7] including couplings of ketenes with imines[8] and with aldehydes.[9,10] Although there are no reports of Nucleophilic Catalysis of [2+2] cycloadditions of ketenes with azo compounds, we were intrigued by the possibility that our planar-chiral pyridines might be effective in this role. In this investigation, we establish that PPY derivative 1 can achieve the first catalytic asymmetric synthesis of aza-β-lactams, via [2+2] cycloadditions of ketenes with azo compounds [Eq. (2)]. (2) As part of our initial study, we examined the cycloaddition of phenyl ethyl ketene with dimethyl azodicarboxylate (1.0 equiv). We were pleased to determine that planar-chiral PPY derivative 1 serves as an effective catalyst for the desired coupling, generating the aza-β-lactam in good ee and yield (Table 1, entry 1; in the absence of a catalyst, there is no reaction: entry 2). Under the same conditions, a related catalyst (2), as well as a variety of chiral phosphines and cinchona alkaloids, provide poor enantioselectivity or little of the cycloaddition product (e.g., entries 3–5).[11,12] The substituents of the azo compound have a significant impact on the ee and the yield, with the methoxycarbonyl group affording the best results (entry 1 vs. entries 6–9). If ClCH2CH2Cl, rather than CH2Cl2, is employed as the solvent, then formation of the aza-β-lactam proceeds less efficiently (entry 1 vs. entry 10). The reaction temperature of choice appears to be −20 °C (entry 1 vs. entries 11–12).[13] Table 1 Nucleophile-catalyzed enantioselective synthesis of aza-β-lactams: Effect of reaction parameters. The optimized conditions can be applied to the enantioselective synthesis of aza-β-lactams from a variety of ketenes (Table 2). If the alkyl group is small (Me or primary), the desired heterocycle is generally produced with good, not excellent, enantioselectivity (~85% ee; entries 1–7). Fortunately, the ee of the aza-β-lactams is readily enhanced by recrystallization (e.g., the product generated from phenyl ethyl ketene can be obtained in >99% ee after a single crystallization; see entry 2 of Table 2). In the case of ketenes that bear a secondary alkyl group, catalyst 1 typically furnishes the aza-β-lactam with very good enantioselectivity and yield (>90% ee; entries 8–13).[14] Table 2 Nucleophile-catalyzed enantioselective synthesis of aza-β-lactams (for the reaction conditions, see [Eq. (2)]). A plausible mechanism for this new nucleophile-catalyzed method for the synthesis of aza-β-lactams is illustrated in Figure 1. Interestingly, the configuration at the quaternary stereocenter is different from that produced in Staudinger reactions that are catalyzed by PPY derivative 1 [Eq. (3)],[8b] which are believed to proceed through a similar pathway.[15] Figure 1 Possible mechanism for the nucleophile-catalyzed synthesis of aza-β-lactams. (3) In conclusion, we have developed a new process, the nucleophile-catalyzed [2+2] cycloaddition of ketenes with azo compounds to generate aza-β-lactams. In addition, we have established that planar-chiral PPY derivative 1 achieves this convergent transformation with good enantioselectivity, thereby providing the first catalytic asymmetric synthesis of this useful family of heterocycles.
-
Enantioselective Nucleophilic Catalysis: The Synthesis of Aza‐β‐Lactams through [2+2] Cycloadditions of Ketenes with Azo Compounds
Angewandte Chemie, 2008Co-Authors: Jacob M Berlin, Gregory C FuAbstract:Although aza-β-lactams have attracted interest due to their biological activity[1] and to their utility as intermediates in organic chemistry (e.g., for the generation of α-amino acids[2] and of hydantoins[3]),[4] only limited progress has been described with regard to the enantioselective synthesis of this family of heterocycles.[5] One attractive, convergent approach to the formation of aza-β-lactams is the [2+2] cycloaddition of a ketene with an azo compound [Eq. (1)].[6] To the best of our knowledge, no stereoselective variants of this process have yet been reported. (1) We have been exploring the use of chiral derivatives of PPY (PPY = 4-(pyrrolidino)pyridine; e.g., 1 and 2) as enantioselective catalysts for an array of transformations,[7] including couplings of ketenes with imines[8] and with aldehydes.[9,10] Although there are no reports of Nucleophilic Catalysis of [2+2] cycloadditions of ketenes with azo compounds, we were intrigued by the possibility that our planar-chiral pyridines might be effective in this role. In this investigation, we establish that PPY derivative 1 can achieve the first catalytic asymmetric synthesis of aza-β-lactams, via [2+2] cycloadditions of ketenes with azo compounds [Eq. (2)]. (2) As part of our initial study, we examined the cycloaddition of phenyl ethyl ketene with dimethyl azodicarboxylate (1.0 equiv). We were pleased to determine that planar-chiral PPY derivative 1 serves as an effective catalyst for the desired coupling, generating the aza-β-lactam in good ee and yield (Table 1, entry 1; in the absence of a catalyst, there is no reaction: entry 2). Under the same conditions, a related catalyst (2), as well as a variety of chiral phosphines and cinchona alkaloids, provide poor enantioselectivity or little of the cycloaddition product (e.g., entries 3–5).[11,12] The substituents of the azo compound have a significant impact on the ee and the yield, with the methoxycarbonyl group affording the best results (entry 1 vs. entries 6–9). If ClCH2CH2Cl, rather than CH2Cl2, is employed as the solvent, then formation of the aza-β-lactam proceeds less efficiently (entry 1 vs. entry 10). The reaction temperature of choice appears to be −20 °C (entry 1 vs. entries 11–12).[13] Table 1 Nucleophile-catalyzed enantioselective synthesis of aza-β-lactams: Effect of reaction parameters. The optimized conditions can be applied to the enantioselective synthesis of aza-β-lactams from a variety of ketenes (Table 2). If the alkyl group is small (Me or primary), the desired heterocycle is generally produced with good, not excellent, enantioselectivity (~85% ee; entries 1–7). Fortunately, the ee of the aza-β-lactams is readily enhanced by recrystallization (e.g., the product generated from phenyl ethyl ketene can be obtained in >99% ee after a single crystallization; see entry 2 of Table 2). In the case of ketenes that bear a secondary alkyl group, catalyst 1 typically furnishes the aza-β-lactam with very good enantioselectivity and yield (>90% ee; entries 8–13).[14] Table 2 Nucleophile-catalyzed enantioselective synthesis of aza-β-lactams (for the reaction conditions, see [Eq. (2)]). A plausible mechanism for this new nucleophile-catalyzed method for the synthesis of aza-β-lactams is illustrated in Figure 1. Interestingly, the configuration at the quaternary stereocenter is different from that produced in Staudinger reactions that are catalyzed by PPY derivative 1 [Eq. (3)],[8b] which are believed to proceed through a similar pathway.[15] Figure 1 Possible mechanism for the nucleophile-catalyzed synthesis of aza-β-lactams. (3) In conclusion, we have developed a new process, the nucleophile-catalyzed [2+2] cycloaddition of ketenes with azo compounds to generate aza-β-lactams. In addition, we have established that planar-chiral PPY derivative 1 achieves this convergent transformation with good enantioselectivity, thereby providing the first catalytic asymmetric synthesis of this useful family of heterocycles.
-
asymmetric Catalysis with planar chiral derivatives of 4 dimethylamino pyridine
Accounts of Chemical Research, 2004Co-Authors: Gregory C FuAbstract:Whereas chiral Lewis acid Catalysis has been intensively investigated, chiral Lewis base (Nucleophilic) Catalysis has been comparatively neglected. We have developed “planar-chiral” derivatives of 4-(dimethylamino)pyridine (DMAP), a highly versatile Nucleophilic catalyst, that are effective in a diverse array of processes, including the Staudinger synthesis of β-lactams, the acylation of silyl ketene acetals, and the kinetic resolution of amines.
-
enantioselective Nucleophilic Catalysis with planar chiral heterocycles
Accounts of Chemical Research, 2000Co-Authors: Gregory C FuAbstract:Although Lewis bases (e.g., tertiary phosphines, tertiary amines, and pyridines) serve as Nucleophilic catalysts for a wide array of reactions, there have been relatively few reports of enantioselective Nucleophilic catalysts. In this Account, we describe the design and synthesis of a new family of chiral Nucleophilic catalysts, specifically, planar-chiral heterocycles. These complexes provide good levels of enantiomeric excess in the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of secondary alcohols.
Simbarashe Ngwerume - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of 2 4 disubstituted imidazoles via Nucleophilic Catalysis
Synlett, 2020Co-Authors: Dmitrii A Shabalin, Simbarashe Ngwerume, Jason E Camp, Jay J Dunsford, Alexandra Rose Saunders, Duncan M GillAbstract:A convergent, microwave-assisted protocol for the synthesis of disubstituted NH-imidazoles via Nucleophilic Catalysis is described. The substituted imidazoles are accessed via the intramolecular addition of a variety of amidoxime substrates to activated alkynes followed by a thermally induced rearrangement of the in situ generated O-vinylamidoxime species. The unprotected imidazoles contain an aryl group at the 2-position as well as an ester moiety at the 4-position.
-
synthesis of highly substituted pyrroles via Nucleophilic Catalysis
ChemInform, 2011Co-Authors: Simbarashe Ngwerume, Jason E CampAbstract:The procedure renders possible a convenient and regioselective access to 2,4-disubstituted, 2,3,5-trisubstituted and tetrasubstituted pyrrole structures as interesting pharmaceutical scaffolds.
-
synthesis of highly substituted pyrroles via Nucleophilic Catalysis
Journal of Organic Chemistry, 2010Co-Authors: Simbarashe Ngwerume, Jason E CampAbstract:A Nucleophilic Catalysis method providing a concise synthesis of di-, tri-, and tetrasubstituted pyrroles is described. This regioselective one-pot method relies on Nucleophilic Catalysis of the intermolecular addition of oximes to activated alkynes and thermal rearrangement of the in situ generated O-vinyl oximes to form pyrroles that contain a functional group handle at the C3/C4 position.
Wenjing Xiao - One of the best experts on this subject based on the ideXlab platform.
-
direct sp3 c h acroleination of n aryl tetrahydroisoquinolines by merging photoredox Catalysis with Nucleophilic Catalysis
ChemInform, 2014Co-Authors: Zhujia Feng, Jun Xuan, Wei Ding, Jiarong Chen, Liangqiu Lu, Wenjing XiaoAbstract:The first example of sequence Catalysis by merging visible light photoredox Catalysis and Nucleophilic Catalysis is reported.
-
Direct sp3 C—H Acroleination of N-Aryl-tetrahydroisoquinolines by Merging Photoredox Catalysis with Nucleophilic Catalysis.
ChemInform, 2014Co-Authors: Zhu‐jia Feng, Jun Xuan, Wei Ding, Liangqiu Lu, Jia‐rong Chen, Wenjing XiaoAbstract:The first example of sequence Catalysis by merging visible light photoredox Catalysis and Nucleophilic Catalysis is reported.
-
direct sp3 c h acroleination of n aryl tetrahydroisoquinolines by merging photoredox Catalysis with Nucleophilic Catalysis
Organic and Biomolecular Chemistry, 2014Co-Authors: Zhujia Feng, Jun Xuan, Wei Ding, Jiarong Chen, Liangqiu Lu, Wenjing XiaoAbstract:Sequence Catalysis merging photoredox Catalysis (PC) and Nucleophilic Catalysis (NC) has been realized for the direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50–91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).
-
Direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox Catalysis with Nucleophilic Catalysis
Organic and Biomolecular Chemistry, 2014Co-Authors: Zhu‐jia Feng, Jun Xuan, Wei Ding, Liangqiu Lu, Jia‐rong Chen, Wenjing XiaoAbstract:Sequence Catalysis merging photoredox Catalysis (PC) and Nucleophilic Catalysis (NC) has been realized for the direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50–91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).
