Organocatalytic Activation of Imines and Related Compounds Through Hydrogen-Bond Interactions

Merino, Pedro; Delso, J. Ignacio; Tejero, Tomás; Roca‐Lopez, David; Isasi, Aranzazu; Matute, Rosa

doi:10.2174/138527211796150660

Cited by 9 publications

(4 citation statements)

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“…Supporting protonation, not hydrogen‐bond activation, Houk et al. described a mechanism and origins of catalysis DFT and experimental study in which a similarly N ‐protonated, to 60 , reactive hydrazonium‐phosphoramide anion (not shown) was formed from a BINOL N ‐triflylphosphoramide and a hydrazone.…”

Section: Methodsmentioning

confidence: 99%

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

et al. 2017

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We report amulti-component asymmetric Brønsted acid-catalyzed aza-Darzens reaction whichi sn ot limited to specific aromatic or heterocyclic aldehydes.I ncorporating alkyld iazoacetates and, important for high ees, ortho-tertbutoxyaniline our optimized reaction (i.e.solvent, temperature and catalyst study) affords excellent yields (61-98 %) and mostly > 90 %o ptically active cis-aziridines.( + +)-Chloramphenicol was generated in 4s teps from commercial starting materials.Atentative mechanism is outlined.Such is the versatility of organocatalysis and its ability to mediate ap lethora of diverse reaction types [1] it is,n ow,a n indispensable "tool" in the synthetic chemists "toolbox". [2] Indeed, improving atom-and reaction-efficiencyi sakey driver to developing new reactions and protocols;i nt his context organocatalysis has demonstrated its importance by efficiently mediating many different convergent reactions or multi-component syntheses.T he work here supports these aspects by generating structure and function-diverse motifs via fewer synthetic, isolation and purification steps.Optically active aziridines have many diverse uses, especially as key intermediates [3] "on route" to important "secondary" products for example, a-/b-amino acids,p olymers,azasugars,auxilaries,oxazolidinones,imidazolidines, blactams and pyrrolidines.F urther applications include synthesis of non-aziridine containing bioactive compounds for example,k ainoids,( À)-mesembrine,( À)-platynesine,a ctinomycin and feldamycin, in addition to synthetic bioactive aziridines for example,NSC676892 as well as natural products for example,azinomycin and maduropeptide. [4] Using aB INOL N-triflylphosphoramide Brønsted acid a6 1-98 %y ielding asymmetric aza-Darzens reaction affords N-aryl-cis-aziridines in, mostly,9 0-99 % ee.T he reaction is straightforward to set up and has minimal requirements for strictly anhydrous or anaerobic conditions,f urthermore it does not require organocatalyst pre-generation or activation, or an "activated" arylglyoxal starting material. Exploiting the protocol synthesis of aziridines based on 4 uses readily generated or commercially available aldehydes (1), amines (2)a nd alkyl diazoacetates (3,Scheme 1).Activating the C = Nb ond of an imine with aB INOL phosphoric acid [5] lowers its LUMO energy and generates an imminium ion pair that can, but not always will, react with an ucleophile.S eminal work by Akiyama et al. established chiral BINOL phosphoric acids [pK a % 13 (CH 3 CN) [6] ]a ctivate aldimines (derived from, specifically,arylglyoxals and panisidine) and react with ethyl diazoacetate (EDA) affording cis-aziridines in 92-97 % ee.[7] Similarly,o ther Brønsted acids [8] and pyridinium triflate activate ad iverse array of imines,i ncluding for example,2 -pyridyl derived 5,e nabling the presumed imminium ion-pair (not shown) to react with EDAa nd afford cis-rac-aziridine (8,8 3% yield) (Scheme 2).[9] With these racemic studies complete our focus shifted to developing asubstrate enhanced and diverse, mult...

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Section: Methodsmentioning

confidence: 99%

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

et al. 2017

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“…In addition, in the previously developed stereoselective PEDA sequence (Figure ), we demonstrated that the photoenols could be stereoselectively trapped by activating the dienophiles by means of H‐bonding interactions with a suitable chiral organocatalyst. Since imines are primed to noncovalent mechanisms of organocatalytic activations, we considered it feasible to develop a stereoselective organocatalytic photoenolization/Mannich‐type process (Figure ). While linear imines proved unreactive, the highly electrophilic cyclic benzoxathiazine‐2,2‐diones 34 intercepted the photoenols generated upon irradiation of 33 by a single black‐light‐emitting diode (black LED, λ max = 365 nm).…”

Section: Organocatalysis For the Enantioselective Intermolecular Tmentioning

confidence: 99%

Organocatalytic Strategies to Stereoselectively Trap Photochemically Generated Hydroxy‐o‐quinodimethanes

Cuadros

Melchiorre

2018

Eur J Org Chem

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Light excitation of ortho‐alkyl aromatic ketones and aldehydes gives access to hydroxy‐o‐quinodimethanes. These reactive electron‐rich intermediates are sufficiently long‐lived to productively engage in chemical processes, mainly acting as dienes in [4+2]‐cycloadditions with electron‐poor alkenes. Since the early discovery of this photoenolization mechanism in 1961, a variety of transformations has been developed, providing a photochemical alternative to classical Diels–Alder chemistry. However, enantioselective catalytic versions of the photenolization/Diels–Alder sequence have remained elusive until recently. This review describes how the field of enantioselective organocatalysis has provided suitable tools to stereoselectively trap photochemically generated hydroxy‐o‐quinodimethanes. Recent studies have also demonstrated that the chemistry is not limited to cycloaddition‐type manifolds, but can be expanded in order to develop intermolecular enantioselective addition processes.

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“…The employment of chiral hydrogen bond donors is a major activation strategy within asymmetric organocatalysis. There are several valuable reviews ,,− that highlight this subject. The most widely employed hydrogen-bonding organocatalysts include chiral-(thio)ureas, diols, phosphoric acids, and various cinchona alkaloid derivatives.…”

Section: Noncovalent Catalysismentioning

confidence: 99%

Enantioselective Organocatalyzed Transformations of β-Ketoesters

et al. 2016

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The β-ketoester structural motif continues to intrigue chemists with its electrophilic and nucleophilic sites. Proven to be a valuable tool within organic synthesis, natural product, and medicinal chemistry, reports on chiral β-ketoester molecular skeletons display a steady increase. With the reignition of organocatalysis in the past decade, asymmetric methods available for the synthesis of this structural unit has significantly expanded, making it one of the most exploited substrates for organocatalytic transformations. This review provides comprehensive information on the plethora of organocatalysts used in stereoselective organocatalyzed construction of β-ketoester-containing compounds.

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Organocatalytic Activation of Imines and Related Compounds Through Hydrogen-Bond Interactions

Cited by 9 publications

References 0 publications

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

Organocatalytic Strategies to Stereoselectively Trap Photochemically Generated Hydroxy‐o‐quinodimethanes

Enantioselective Organocatalyzed Transformations of β-Ketoesters

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