Practical Implications of Boron‐to‐Zinc Transmetalation for the Catalytic Asymmetric Arylation of Aldehydes

Jimeno, Ciril; Sayalero, Sonia; Fjermestad, Torstein; Colet, Gisela; Maseras, Feliu; Pericàs, Miquel À.

doi:10.1002/anie.200703103

Cited by 85 publications

(32 citation statements)

References 38 publications

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“…Dimethyl (polyethylene glycol) (DiMPEG, 10 mol %, MW∼2,000) was used as an additive to inhibit the background reaction caused by achiral Lewis acidic ZnPh 2 or ZnBr 2 43,49,50. Further study and optimization by the groups of Pericàs and Magnus significantly reduced the transmetallation time 51,52. Braga demonstrated that the acceleration could be achieved by microwave irradiation 53.…”

Section: Introductionmentioning

confidence: 99%

Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl-, and Diheteroarylmethanols

2009

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Enantioenriched diaryl-, aryl heteroaryl-and diheteroarylmethanols exhibit important biological and medicinal properties. One-pot catalytic asymmetric syntheses of these compounds beginning from readily available aryl bromides are introduced. Thus, lithium-bromide exchange with commercially available aryl bromides and n-BuLi was followed by salt metathesis with ZnCl 2 to generate ArZnCl. A second equivalent of n-BuLi was added to form the mixed organozinc, ArZnBu. In the presence of enantioenriched amino alcohol-based catalysts, ArZnBu adds to aldehydes to afford essentially racemic diarylmethanols. The low enantioselectivities were attributed to a LiCl-promoted background reaction. To inhibit this background reaction, the chelating diamine TEEDA (tetraethylethylene diamine) was introduced prior to aldehyde addition. Under these conditions, enantioenriched diarylmethanols were obtained with >90% ee. Arylations of enals generated allylic alcohols with 81-90% ee. This procedure was unsuccessful, however, when applied to heteraryl bromides, which was attributed to decomposition of the heteroaryl lithium under the salt metathesis conditions. To avoid this problem, the metathesis was conducted with EtZnCl, which enabled the salt metathesis to proceed at low temperatures. The resulting EtZn(Ar Hetero ) intermediates (Ar Hetero =2-and 3-thiophenyl, 2-benzothiophenyl, 3-furyl, and 5-indolyl) were successfully added to aldehydes and heteroaryl aldehydes with enantioselectivities between 81-99%. These are the first examples of catalytic and highly enantioselective syntheses of diheteroarylmethanols. In a similar fashion, ferrocenyl bromide was used to generate FcZnEt and the ferrocenyl group added to benzaldehyde and heteroaromatic aldehydes to form ferrocene-based ligand precursors in 86-95% yield with 96-98% ee. It was also found that the arylation and heteroarylation of enals could be followed by diastereoselective epoxidations to provide epoxy alcohols with high enantio-and diastereoselectivities in a one-pot procedure.

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Section: Introductionmentioning

confidence: 99%

Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl-, and Diheteroarylmethanols

2009

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“…Ethylation/cyclopropanation of α-phenyl enals Scheme 3. One-pot method for the synthesis of 1,2,3-substituted cyclopropanes from enals Initially, the phenyl(ethyl)zinc species was generated in situ through transmetallation between triphenylboroxin and diethylzinc in toluene at 60ºC for 30 min, 21 and subsequently the addition of the aldehyde to the reaction mixture in the previously reported optimal conditions 18b was carried out. Next, instead of quenching the zinc alkoxide, the cyclopropanation of the double bound was performed at room temperature in light exclusion without the need of removing the boron species.…”

Section: Resultsmentioning

confidence: 99%

Tandem diastereo- and enantioselective preparation of aryl and alkyl cyclopropyl carbinols with three adjacent stereocenters using perhydrobenzoxazines and diethylzinc

2014

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The enantio-and diastereoselective one-pot ethylation/cyclopropanation is efficiently promoted by a chiral perhydrobenzoxazine. The catalytic system tolerates a wide range of di-and trisubstituted α,β-unsaturated aldehydes and has been found to be highly diastereo-and enantioselective. Enals leading to intermediates lacking allylic strain or with either A 1,2 or A 1,3 strain afford the corresponding syn hydroxycyclopropanes very selectively. While α-methyl enals are successfully ethylated/cyclopropanated, the presence of bulky substituents at alpha position of the enal constitutes a limitation to the substrate scope. The use of 1,1-diiodoethane allows the obtention of the corresponding enantioenriched cyclopropylcarbinol, which bears carbon-substituents at all three positions of the ring, with good enantiocontrol, although moderate diastereoselectivity. A procedure for the asymmetric one-pot arylation/cyclopropanation of enals is proposed, which involves the use of triarylboroxin, diethylzinc and diiodomethane.

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“…In 2008 we published that triarylboroxins undergo a scrambling process with Et 2 Zn that generates in situ the corresponding arylzinc species. This strategy greatly simplified the arylation of aldehydes, avoiding the use of expensive and difficult to prepare diarylzinc derivatives . Hence, we reasoned that integrating this approach with the knowledge acquired on the previous work with ligand 25 would allow to carry out the enantioselective continuous arylation of aldehydes with triarylboroxins as the ultimate source of aryl groups.…”

Section: Immobilized Ligands and Metal‐based Catalysts For Work In Flowmentioning

confidence: 99%

Catalytic Enantioselective Flow Processes with Solid‐Supported Chiral Catalysts

Rodríguez‐Escrich

Pericàs

2018

The Chemical Record

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Sustainability concerns are the wind in the sails for the development of novel, more selective catalytic processes. Hence, chiral catalysts play a crucial role in the green production of enantioenriched compounds. To further increase the green profile of this approach, the use of solid-supported catalytic species is appealing due to the reduced generation of waste, as well as the possibility of reusing the precious catalyst. Even more attractive is the implementation of flow processes based on these immobilized catalysts, a flexible strategy that allows to generate from milli- to multi-gram amounts of chiral product with a reduced footprint set-up. Herein, we will present the efforts devoted in our laboratory towards the immobilization of chiral catalysts and their use in single-pass, highly enantioselective, flow processes. Proline, diarylprolinols, other aminocatalysts, squaramides, thioureas, phosphoric acids and even chiral ligands and metal-based catalysts constitute our current toolkit of supported species for enantioselective catalysis.

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Practical Implications of Boron‐to‐Zinc Transmetalation for the Catalytic Asymmetric Arylation of Aldehydes

Cited by 85 publications

References 38 publications

Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl-, and Diheteroarylmethanols

Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl-, and Diheteroarylmethanols

Tandem diastereo- and enantioselective preparation of aryl and alkyl cyclopropyl carbinols with three adjacent stereocenters using perhydrobenzoxazines and diethylzinc

Catalytic Enantioselective Flow Processes with Solid‐Supported Chiral Catalysts

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