3,4-Dihydroxypyrrolidines via Modified Tandem Aza-Payne/Hydroamination Pathway

Kulshrestha, Aman; Marzijarani, Nastaran Salehi; Ashtekar, Kumar Dilip; Staples, Richard J.; Borhan, Babak

doi:10.1021/ol301204w

Cited by 18 publications

(6 citation statements)

References 19 publications

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“…Intriguingly, intramolecular animation has been explored using NaH, KO t Bu and (dimethyl (oxo)-λ-sulfanylidene) methane bases for the synthesis of isothiazoles, indoles and pyrrolidines, respectively (Scheme G–I). The Borhan group has established a tandem aza-Payne pathway followed by a hydroamination reaction via a latent nucleophile.…”

Section: Progress In Base-mediated Hydroamination Chemistrymentioning

confidence: 99%

Base-Mediated Hydroamination of Alkynes

2017

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Inter- or intramolecular hydroamination reactions are a paradigmatic example of modern sustainable organic chemistry, as they are a catalytic, 100% atom-economical, and waste-free process of fundamental simplicity in which an amine is added to an alkyne substrate. Many enamines are found in many natural and synthetic compounds possessing interesting physiological and biological activities. The development of synthetic protocols for such molecules and their transformation is a persistent research topic in pharmaceutical and organic chemistry. Hydroamination is conspicuously superior to the other accessible methods, such as the imination of ketones or the aminomercuration/demercuration of alkynes, that involve the stoichiometric use of toxic reagents. Additionally, the hydroamination of alkyne substrates has been successfully employed as a key step in synthesizing target molecules through total syntheses containing substituted indoles, pyrroles, imidazoles, and other heterocycles as core moieties. Many research groups have explored inter- or intramolecular hydroamination of alkynes for the synthesis of diversely substituted nitrogen heterocycles using expensive metal catalysts. However, in contrast to metal-catalyzed hydroamination, the base-mediated hydroamination of alkynes has not been extensively studied. Various inorganic (such as hydroxides, phosphates, and carbonates) and organic bases have been proven to be valuable reagents for achieving the hydroamination process. This method represents an attractive strategy for the construction of a broad range of nitrogen-containing compounds that prevents the formation of byproducts in the creation of a C-N linkage. The presence of a base is thought to facilitate the attack of nitrogen nucleophiles, such as indoles, pyrroles, and imidazoles, on unsaturated carbon substrates through the activation of the triple bond and thus transforming the electron-rich alkyne into an electrophile. In the past few years, we have been involved in the development of methods for the nucleophilic addition of N-heterocycles onto terminal and internal alkynes using alkali base catalysts to achieve new carbon-nitrogen bond-forming reactions. During our study, we discovered the regioselective preferential nucleophilic addition of N-heterocycles onto the haloarylalkyne over N-arylation of the aryl halide. In this Account, we summarize our latest achievements in regio-, stereo-, and chemoselective hydroamination chemistry of N-nucleophiles with alkynes using a superbasic medium to produce a broad range of highly functionalized vinyl and styryl enamines, which are valuable and versatile synthetic intermediates for the synthesis of bioactive compounds. Interestingly, the stereoselectivity of the addition products (kinetically stable Z and thermodynamically stable E isomers) was found to be dependent upon time. It is worthwhile to note that hydroaminated products formed by the addition reaction can further be utilized for the synthesis of indolo-/pyrrolo[2,1-a]isoquinolines, naphthyridines, and b...

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Section: Progress In Base-mediated Hydroamination Chemistrymentioning

confidence: 99%

Base-Mediated Hydroamination of Alkynes

2017

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“…Borhan and co-workers extensively studied the aza-Payne/hydroaminationmodified hydroamination reaction of aziridinols for the synthesis of highly substituted fused pyrrolidines [79][80][81][82]. They reported dimethylsulfoxonium ylidebased aza-Payne rearrangement of 2,3-disubstituted aziridinols for the synthesis of highly functionalized pyrrolidine derivatives [79].…”

Section: Synthesis Of Pyrrolidine Derivativesmentioning

confidence: 99%

Ring Expansions of Activated Aziridines and Azetidines

Ghorai

Bhattacharyya

Das

et al. 2015

Topics in Heterocyclic Chemistry

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Facile construction of small and normal-sized, or more precisely, four to seven-membered aza-heterocyclic ring systems is always a challenging yet rewarding task for the synthetic organic chemists. Fortunately, activated aziridines and azetidines provide a direct and convenient access to this coveted molecular architectures through several elegant ring-expansion approaches. This chapter presents some of the illustrative and contemporary examples to demonstrate the synthetic diversity and efficiency of the ring-expansion strategies of activated aziridines and azetidines towards a vast array of small to normal-sized aza-heterocyclic moieties.

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“…Me 2 PhSiBpin, 3 and McQuade's catalysts L3•CuCl 13b and L4•CuCl 14a were prepared according to reported procedures. Standard literature procedures were used for the preparation of allylic alcohols en route to 1a, 18 1b, 19 and 1c. 20 Phosphorylation of allylic alcohols was carried out according to our previous communication.…”

Section: Scheme 2 Regio-and Enantioselective Copper(i)-catalyzed S N mentioning

confidence: 99%

“…However, lowering the reaction temperature to -35°C yielded (R)-2a with 93% ee and 91:9 selectivity in favor of the γ-regioisomer in reasonable 43% yield; the temperature was detrimental to conversion. Next, the position of the methyl substituent was changed from the β-to the γ-carbon atom [1b → (R)-2b, Table 1, entries [11][12][13][14][15][16][17][18]. Allylic silylation would lead to the installation of the silicon group at a fully substituted carbon atom.…”

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confidence: 99%

McQuade’s Six-Membered NHC–Copper(I) Complexes for Catalytic Asymmetric Silyl Transfer

2014

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A full account of our work on enantioselective silylation of typical prochiral acceptors employing chiral six-membered NHC-copper(I) complexes introduced by McQuade and co-workers is presented. With these precatalysts, asymmetric branched-selective substitution of allylic phosphates and 1,2-addition to imines had become possible for the first time. The successful application of these catalysts in two fundamentally different reactions raised the question whether these are a privileged ligand motif for catalytic asymmetric silyl transfer. To assess their generality, these were utilized in the related 1,2-addition to aldehydes and in conjugate addition to representative α,β-unsaturated acceptors, but with limited success in both cases. This study also includes an optimization of the allylic silylation, now overcoming the limited scope of the previous protocol. The scope of the imine addition is extended to heteroaryl-substituted aldimines.The formation of silicon nucleophiles by activation of the silicon-boron interelement linkage through transmetalation with transition metal-oxygen bonds has added an invaluable tool to the arsenal of catalytic carbon-silicon bond-forming processes. 1,2 Among the transformations on the basis of this concept, catalytic asymmetric variants are particularly desirable, but had remained underdeveloped just until recently. Studies from our laboratory revealed that a chiral diphosphine-[Rh I -OH] complex activates Suginome's silyl boronic ester, Me 2 PhSiBpin (pin = pinacolato), 3 and subsequently transfers the rhodium(I)-bound silyl anion to α,β-unsaturated cyclic carbonyl/carboxyl as well as Z-configured acyclic carboxyl compounds in highly enantioselective fashion. 4 Regrettably, we had not been able to apply this catalytic system to reactions other than conjugate addition. By changing the transition metal from rhodium(I) to copper(I), Hoveyda and co-workers elaborated a related, broadly applicable 1,4-addition catalyzed by an in situ-generated chiral NHC-[Cu I -Ot-Bu] complex (Scheme 1, upper left). 5-7 Parallel to this development, our group demonstrated that transmetalation with [Cu I -OR] complexes is not limited to conjugate addition. The straightforward combination of CuCN/NaOMe without any phosphine or NHC as supporting ligand releases a highly reactive silicon-based cuprate from the silicon-boron pronucleophile that cleanly adds to allylic 8 and propargylic substrates 9 by selective S N 2′ displacement as well as to imines 10 and aldehydes 11 by 1,2-addition. The latter was later rendered enantioselective by Riant and co-workers using an unprecedented copper(I) bifluoride complex with DTBM-Segphos (L2) as chiral ligand and an excess of MeOH (Scheme 1, lower left). 12 Both aryl-and alkylsubstituted aldehydes were converted into the corresponding α-hydroxysilanes with high enantiomeric excesses and in good chemical yields. During our attempts to perform the branched-selective copper(I)-catalyzed allylic substitution enantioselectively, we became aware of the chiral six-membered NH...

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3,4-Dihydroxypyrrolidines via Modified Tandem Aza-Payne/Hydroamination Pathway

Cited by 18 publications

References 19 publications

Base-Mediated Hydroamination of Alkynes

Base-Mediated Hydroamination of Alkynes

Ring Expansions of Activated Aziridines and Azetidines

McQuade’s Six-Membered NHC–Copper(I) Complexes for Catalytic Asymmetric Silyl Transfer

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3,4-Dihydroxypyrrolidines via Modified Tandem Aza-Payne/Hydroamination Pathway

Cited by 18 publications

References 19 publications

Base-Mediated Hydroamination of Alkynes

Base-Mediated Hydroamination of Alkynes

Ring Expansions of Activated Aziridines and Azetidines

McQuade’s Six-Membered NHC–Copper(I) Complexes for Catalytic Asymmetric­ Silyl Transfer

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Product

Resources

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McQuade’s Six-Membered NHC–Copper(I) Complexes for Catalytic Asymmetric Silyl Transfer