Correlation Between pK<sub>a</sub> and Reactivity of Quinuclidine‐Based Catalysts in the Baylis—Hillman Reaction: Discovery of Quinuclidine as Optimum Catalyst Leading to Substantial Enhancement of Scope.

Aggarwal, Varinder K.; Emme, Ingo; Fulford, Sarah Y.

doi:10.1002/chin.200320031

Cited by 4 publications

(6 citation statements)

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“…Spectral data is consistent with literature values. 24 1 H NMR (400 MHz, CDCl 3 ) δ 8.27-8.15 (m, 2H), 7.64-7.54 (m, 2H), 6.77 (t, J = 4.3 Hz, 1H), 5.66 (d, J = 4.9 Hz, 1H), 4.44-4.33 (m, 2H), 3.63 (d, J = 5.5 Hz, 1H), 2.62-2.47 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 164.5, 148.3, 147.6, 141.8, 134.2, 127.5, 123.8, 71.8, 66.5, 24.3.…”

Section: Methodsmentioning

confidence: 99%

“…Testament to its catalytic power, BH32.14 can even promote enantioselective transformations of unsaturated lactones (product 5b ), which are notoriously challenging as MBH substrates. 24 , 25 BH32.14 also accepts a range of mono- and di-substituted aromatic aldehydes as substrates, although has a clear preference for para -substituted derivatives. While a modestly electron-donating p -Me substituent is well tolerated ( 5i ), introduction of a strongly donating p -OMe group leads to a significant reduction in activity ( 5j ).…”

Section: Synthetic Utility Of Engineered Mbhasesmentioning

confidence: 99%

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Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

et al. 2021

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The combination of computational design and directed evolution could offer a general strategy to create enzymes with new functions. To date, this approach has delivered enzymes for a handful of model reactions. Here we show that new catalytic mechanisms can be engineered into proteins to accelerate more challenging chemical transformations. Evolutionary optimization of a primitive design afforded an efficient and enantioselective enzyme (BH32.14) for the Morita-Baylis-Hillman (MBH) reaction. BH32.14 is suitable for preparative scale transformations, accepts a broad range of aldehyde and enone coupling partners, and is able to promote selective mono-functionalizations of dialdehydes. Crystallographic, biochemical and computational studies reveal that BH32.14 operates via a sophisticated catalytic mechanism comprising a His23 nucleophile paired with a judiciously positioned Arg124. This catalytic arginine shuttles between conformational states to stabilize multiple oxyanion intermediates and serves as a genetically encoded surrogate of privileged bidentate hydrogen bonding catalysts (e.g. thioureas). This study demonstrates that elaborate catalytic devices can be built from scratch to promote demanding multi-step processes not observed in Nature.

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Section: Methodsmentioning

confidence: 99%

Section: Synthetic Utility Of Engineered Mbhasesmentioning

confidence: 99%

Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

et al. 2021

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“…The 1 H NMR comparison of PTHF-1b with PTHF-Ib (see Figure S3, top and middle, respectively) showed the shift of the N + -adjacent methylene proton signals from 3.90/4.10 ppm to 4.30/4.82 ppm and of the phenyl proton signal from 7.43 to 7.70 ppm, respectively, for PTHF-Ib. The one-step production of a zwitterionic poly(THF) precursor PTHF-Ia was reasoned by the significantly high basicity of an aliphatic amine of quinuclidine (pK a of 11.38) 35 against an aniline derivative of N-phenylpyrrolidine (pK a of 5.22). 36 The deprotonation of PTHF-1b was confirmed also by the IR examination, where the triflate absorptions at 638 and 1030 cm −1 were removed along with the DBU treatment (Figure S4).…”

Section: Preparation Of Telechelic Poly(thf)s Having a Cyclicmentioning

confidence: 99%

Synthesis and Unimolecular ESA-CF Polymer Cyclization of Zwitterionic Telechelic Precursors

et al. 2019

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A series of zwitterionic polystyrene (PS) and poly(THF) telechelics having a pair of a cyclic ammonium and a carboxylate end groups have been prepared by making use of a living anionic and cationic polymerization technique, respectively, and have been applied for effective polymer cyclization through the unimolecular ESA-CF (electrostatic self-assembly and covalent fixation) protocol. Thus, a telechelic polystyrene (PS) having a hydroxyl and a methyl ester group (PS-1) was prepared by a living anionic polymerization technique, and the subsequent triflate esterification of the hydroxyl group and the quaternization either by quinuclidine or N-phenylpyrrolidine were conducted to give two types of telechelic precursors, PS-2a and PS-2b, having a respective cyclic ammonium unit and a methyl ester unit. The methyl ester end group in PS-2a and PS-2b was then converted into a carboxylic acid group by the treatment with boron tribromide to afford PS-3a and PS-3b, respectively. On the other hand, the relevant telechelic poly(THF)s having a pair of cyclic ammonium and carboxylic acid groups, PTHF-1a and PTHF-1b, were obtained conveniently through a living cationic ring-opening polymerization of THF with a triflate ester derivative having a carboxylic acid unit, followed by the end-capping by moderately strained cyclic amines. The effective unimolecular ESA-CF polymer cyclization was performed under various dilutions by employing zwitterionic telechelic PS and poly(THF) precursors, PS-Ia and -Ib as well as PTHF-Ia and -Ib, obtained in situ by the deprotonation of the carboxylic acid unit in PS-3 or PTHF-1 with a strong base like DBU or with an excess of quinuclidine to produce cyclic PS and poly(THF) products of different linking units, PS-IIa and -IIb as well as PTHF-IIa and -IIb, in satisfactory yields.

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“…In the past decades, remarkable advances in this area have led to the discovery of several new catalysts with superior activities and enantioselectivities [12 -20] . Meanwhile, efforts have also been made to investigate the reaction mechanism [21][22][23][24][25][26][27][28][29][30][31] . Generally, the reaction is catalyzed by a tertiary amine or tertiary phosphine, and the commonly accepted mechanism is shown in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

“…was proposed to be the aldol addition step based on kinetic isotope data. Later on, protic additives were found to promote the reaction [32][33][34][35][36][37][38][39][40][41] and autocatalysis was observed in the absence of protic additives [23] . A modified mechanism was then proposed by Aggarwal and coworkers.…”

Section: Introductionmentioning

confidence: 99%

Bifunctional catalysis of Morita-Baylis-Hillman (MBH) reaction with chiral primary-tertiary diamine: A non-typical MBH catalytic pathway

Zhang

Luo

Chen

et al. 2009

Sci. China Ser. B-Chem.

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Correlation Between pK_a and Reactivity of Quinuclidine‐Based Catalysts in the Baylis—Hillman Reaction: Discovery of Quinuclidine as Optimum Catalyst Leading to Substantial Enhancement of Scope.

Cited by 4 publications

References 1 publication

Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

Synthesis and Unimolecular ESA-CF Polymer Cyclization of Zwitterionic Telechelic Precursors

Bifunctional catalysis of Morita-Baylis-Hillman (MBH) reaction with chiral primary-tertiary diamine: A non-typical MBH catalytic pathway

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Correlation Between pKa and Reactivity of Quinuclidine‐Based Catalysts in the Baylis—Hillman Reaction: Discovery of Quinuclidine as Optimum Catalyst Leading to Substantial Enhancement of Scope.

Cited by 4 publications

References 1 publication

Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction

Synthesis and Unimolecular ESA-CF Polymer Cyclization of Zwitterionic Telechelic Precursors

Bifunctional catalysis of Morita-Baylis-Hillman (MBH) reaction with chiral primary-tertiary diamine: A non-typical MBH catalytic pathway

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Correlation Between pK_a and Reactivity of Quinuclidine‐Based Catalysts in the Baylis—Hillman Reaction: Discovery of Quinuclidine as Optimum Catalyst Leading to Substantial Enhancement of Scope.