Addition of Carboxylic Acids to gem-Difluoroalkenes for the Synthesis of gem-Difluoromethylenated Compounds.

We herein describe a straightforward protocol for the synthesis of carboxylic esters containing a gem-difluoromethylene unit. Readily available carboxylic acids can act as nucleophiles to add regioselectively to tetrasubstituted or trisubstituted ß,ß-difluoroacrylates (formal hydroacetoxylation) for the construction of RCO2-CF2 bonds. Thermal conditions are sufficient without the use of catalysts or additives.

Artificial Intelligence-Powered Construction of a Microbial Optimal Growth Temperature Database and Its Impact on Enzyme Optimal Temperature Prediction.

Accurate prediction of enzyme optimal temperature (Topt) is crucial for identifying enzymes suitable for catalytic functions under extreme bioprocessing conditions. The optimal growth temperature (OGT) of microorganisms serves as a key indicator for estimating enzyme Topt, reflecting an evolutionary temperature balance between enzyme-catalyzed reactions and the organism's growth environments. Existing OGT databases, collected from culture collection centers, often fall short as culture temperature does not precisely represent the OGT. Models trained on such databases yield inadequate accuracy in enzyme Topt prediction, underscoring the need for a high-quality OGT database. Herein, we developed AI-based models to extract the OGT information from the scientific literature, constructing a comprehensive OGT database with 1155 unique organisms and 2142 OGT values. The top-performing model, BioLinkBERT, demonstrated exceptional information extraction ability with an EM score of 91.00 and an F1 score of 91.91 for OGT. Notably, applying this OGT database in enzyme Topt prediction achieved an R2 value of 0.698, outperforming the R2 value of 0.686 obtained using culture temperature. This emphasizes the superiority of the OGT database in predicting the enzyme Topt and underscores its pivotal role in identifying enzymes with optimal catalytic temperatures.

Palladium-Catalyzed Stereoselective Defluoroborylation of gem-Difluoroalkenes with Unsymmetrical Diboron: Access to Tetrasubstituted Monofluorinated Vinyl-B(dan) Derivatives.

The stereoselective C-F bond borylation of tetrasubstituted ß,ß-difluoroacrylates has been achieved. In contrast to the previously used B2pin2 reagent, which only led to dimerization products, this work employs the unsymmetrical diboron reagent (pin)B-B(dan) under the palladium(0)-catalyzed conditions to access novel boronamides containing the monofluorinated vinyl-B(dan) functionality. These compounds can cross-couple directly with gem-difluoroalkenes without reactivation in Suzuki-Miyaura reactions to afford vincinal difluoro 1,3-dienes with modular control of the substituents.

Palladium-Catalyzed Stereoselective Defluorosilylation of gem-Difluoroalkenes for the Synthesis of Tetrasubstituted Monofluorinated Vinylsilanes.

Stereoselective synthesis of tetrasubstituted vinylsilanes is a challenging task. We herein report a novel palladium(0)-catalyzed defluorosilylation of ß,ß-difluoroacrylates to access tetrasubstituted vinylsilanes containing the monofluoroalkene motif in excellent diastereoselectivities (>99:1). This is our first example of C-heteroatom bond formation from the C-F bond under such a Pd catalytic manifold.

Stereoselective Rhodium(I)-Catalyzed C-F Bond Arylation of Tri- and Tetrasubstituted gem-Difluoroalkenes with Boronic Acids.

We herein describe a highly diastereoselective rhodium(I)-catalyzed C-F bond functionalization of gem-difluoroalkenes with arylboronic acids. In contrast to previously developed Pd(II)- and Pd(0)-catalyzed methods, the Rh(I)/BINAP catalytic system enabled the C-F bond arylation of both trisubstituted ß,ß-difluorostyrenes and tetrasubstituted ß,ß-difluoroacrylates in >99:1 dr toward the synthesis of valuable monofluoroalkenes. Experimental and computational studies suggested a plausible migratory insertion/ß-F elimination mechanism with the [Rh(I)-Ar] species.

Highly Selective C-F Bond Functionalization of Tetrasubstituted gem-Difluoroalkenes and Trisubstituted Monofluoroalkenes Using Grignard Reagents.

We herein describe selective C-F bond functionalizations of tetrasubstituted gem-difluoroalkenes and trisubstituted monofluoroalkenes using Grignard reagents without the transition metal catalyst. ß,ß-Difluoroacrylates react with Grignard reagents under mild conditions to afford tetrasubstituted (E)-ß-monofluoroacrylates. Experimental and computational studies revealed that the selectivity stems from the intrinsic reactivity difference between the (E)- and (Z)-isomers toward excess Grignard reagent, which leads to the resolution of the two products.

Rhodium(I)-Catalyzed Defluorinative Coupling of Boronic Acids with Monofluoroalkenes.

We herein describe a highly selective Rh(I)-catalyzed defluorinative coupling of boronic acids with (E)-ß-monofluoroacrylates. In contrast to previous methods, the trisubstituted (Z)-alkene products were obtained in excellent dr with an inversion of double bond geometry. Experimental and computational studies established that Rh(I)-facilitated ß-F elimination is favored over competing ß-H elimination and protodemetalation.

Nucleophilic Vinylic Substitution (SNV) of Trisubstituted Monofluoroalkenes for the Synthesis of Stereodefined Trisubstituted Alkenes and Divinyl Ethers.

We herein describe a nucleophilic vinylic substitution (SNV) of trisubstituted monofluoroalkenes with excellent stereocontrol (d.r. > 99:1). Starting from (E)-ß-monofluoroacrylates, various trisubstituted (E)-alkenes containing O/N/S-substituent groups at the vinylic position can be obtained under simple conditions. Furthermore, (E,E)-divinyl ethers can be generated through dimerization of the monofluoroalkenes, triggered by adventitious water in the reaction mixture.