Photoredox-Catalyzed Preparation of Sulfones Using Bis-Piperidine Sulfur Dioxide - An Underutilized Reagent for SO2 Transfer.

Sulfonyl groups are widely observed in biologically relevant molecules and consequently, SO2 capture is an increasingly attractive method to prepare these sulfonyl-containing compounds given the range of SO2 -surrogates now available as alternatives to using the neat gas. This, along with the advent of photoredox catalysis, has enabled mild radical capture of SO2 to emerge as an effective route to sulfonyl compounds. Here we report a photoredox-catalyzed cross-electrophile sulfonylation of aryl and alkyl bromides making use of a previously under-used amine-SO2 surrogate; bis(piperidine) sulfur dioxide (PIPSO). A broad selection of alkyl and aryl bromides were photocatalytically converted to their corresponding sulfinates and then trapped with various electrophiles in a one-pot multistep procedure to prepare sulfones and sulfonamides.

Nitro-sulfinate Reductive Coupling to Access (Hetero)aryl Sulfonamides.

A method to assemble (hetero)aryl sulfonamides via the reductive coupling of aryl sulfinates and nitroarenes is reported. Various reducing conditions with sodium bisulfite and with or without tin(II) chloride in DMSO were developed using an ultrasound bath to improve reaction homogeneity and mixing. A range of (hetero)aryl sulfonamides bearing a selection of functional groups were prepared, and the mechanism of the transformation was investigated. These investigations have led us to propose the formation of nitrosoarene intermediates, which were established via an independent molecular coupling strategy.

Photoredox-Catalyzed Dehydrogenative Csp3-Csp2 Cross-Coupling of Alkylarenes to Aldehydes in Flow.

Executing photoredox reactions in flow offers solutions to frequently encountered issues regarding reproducibility, reaction time, and scale-up. Here, we report the transfer of a photoredox-catalyzed benzylic coupling of alkylarenes to aldehydes to a flow chemistry setting leading to improvements in terms of higher concentration, shorter residence times, better yields, ease of catalyst preparation, and enhanced substrate scope. Its applicability has been demonstrated by a multi-gram-scale reaction using high-power light-emitting diodes (LEDs), late-stage functionalization of selected active pharmaceutical ingredients (APIs), and also a photocatalyst recycling method.

Regioselective and Stereoselective Heck-Matsuda Arylations of Trisubstituted Allylic Alkenols and Their Silyl and Methyl Ether Derivatives To Access Two Contiguous Stereogenic Centers: Expanding the Redox-Relay Process and Application in the Total Synthesis of meso-Hexestrol.

Novel palladium-catalyzed redox-relay Heck arylation reactions of trisubstituted allylic alkenols were developed employing silyl and methyl ethers. The reactions proceeded under mild conditions in moderate to high yields in an excellent anti diastereoselectivity to form α,ß-disubstituted methyl ketones containing two contiguous stereocenters. The new redox-relay arylations using silyl and methyl ethers of the starting alkenols demonstrate that the presence of a free hydroxyl group is not a sine qua non condition for an effective redox-relay process as previously thought. Deuterium-labeled alkenols 2-d-10a, 2-d-10b, and 2-d-10c permitted tracking the palladium-hydride reinsertion steps in the conversion of the starting free alcohols, silyl, and methyl ethers into the corresponding methyl ketone 3-d-11a, with >98% deuterium retention. Moreover, the synthetic potential of the method was demonstrated with a straightforward synthesis of the meso-hexestrol in 4 steps, in 41% overall yield from alkenol 10a.

Synthesis of unprotected glyco-alkynones via molybdenum-catalyzed carbonylative Sonogashira cross-coupling reaction.

Herein we report a novel Mo-catalyzed carbonylative Sonogashira cross-coupling between 2-iodoglycals and terminal alkynes. The reaction displays major improvements compared to a related Pd-catalyzed procedure previously published by our group, such as utilizing unprotected sugar derivatives as starting materials and tolerance to substrates bearing chelating groups. In this work we also demonstrate the utility of the glyco-alkynone products as platform for further functionalization by synthesizing glyco-flavones via Au-catalyzed 6-endo-dig cyclization.

Synthesis of unprotected glyco-alkynones via molybdenum-catalyzed carbonylative Sonogashira cross-coupling reaction

Herein we report a novel Mo-catalyzed carbonylative Sonogashira cross-coupling between 2-iodoglycals and terminal alkynes. The reaction displays major improvements compared to a related Pd-catalyzed procedure previously published by our group, such as utilizing unprotected sugar derivatives as starting materials and tolerance to substrates bearing chelating groups. In this work we also demonstrate the utility of the glyco-alkynone products as platform for further functionalization by synthesizing glyco-flavones via Au-catalyzed 6-endo-dig cyclization.

Palladium-catalyzed thio- and selenocarbonylation of 2-iodoglycals

The carbonylative cross-coupling reactions of 2-iodoglycals with thiols and selenols in the presence of molybdenum hexacarbonyl as a solid source of carbon monoxide is described. This methodology permitted the synthesis of 29 C2-glycosides bearing thioester and selenoester functionalities in moderate to excellent yields and high functional group tolerance. Moreover, this communication describes the first catalytic carbonylative coupling reaction of selenols with a carbon electrophile.

Stereo- and regioselective cu-catalyzed hydroboration of alkynyl chalcogenoethers

A mild stereo- and regioselective Cu-catalyzed hydroboration method for the synthesis of (Z)-seleno-alkenyl boronates and (Z)-thio-alkenylboronates from internal alkynes in the presence of commercially available B2pin2 is presented. This highly selective transformation relies on the use of N-heterocyclic carbene (NHC) complex IPrCuCl as the active catalytic species. We also explore the functionalization of the alkenylboronates obtained via oxidation to give a -chalcogeno ketones, useful building blocks for the synthesis of more complex chalcogen-containing molecules.

Palladium-catalyzed thio- and selenocarbonylation of 2-iodoglycals

The carbonylative cross-coupling reactions of 2-iodoglycals with thiols and selenols in the presence of molybdenum hexacarbonyl as a solid source of carbon monoxide is described. This methodology permitted the synthesis of 29 C2-glycosides bearing thioester and selenoester functionalities in moderate to excellent yields and high functional group tolerance. Moreover, this communication describes the first catalytic carbonylative coupling reaction of selenols with a carbon electrophile.

Carbonylative negishi-type coupling of 2-Iodoglycals with alkyl and aryl halides

C-Glycosides are valuable organic compounds in the field of medicinal chemistry due to their ubiquity inside living systems and pronounced biological activity. Herein, we describe an approach to alkyl-ketones bearing glycal units via the Pd-catalyzed carbonylative coupling of 2-iodoglycals and alkyl and aryl halides. Examples bearing a variety of functional groups are presented as well as a mechanistic proposal for this transformation.

Stereo- and regioselective cu-catalyzed hydroboration of alkynyl chalcogenoethers

A mild stereo- and regioselective Cu-catalyzed hydroboration method for the synthesis of (Z)-seleno-alkenyl boronates and (Z)-thio-alkenylboronates from internal alkynes in the presence of commercially available B2pin2 is presented. This highly selective transformation relies on the use of N-heterocyclic carbene (NHC) complex IPrCuCl as the active catalytic species. We also explore the functionalization of the alkenylboronates obtained via oxidation to give a -chalcogeno ketones, useful building blocks for the synthesis of more complex chalcogen-containing molecules.

Carbonylative negishi-type coupling of 2-Iodoglycals with alkyl and aryl halides

C-Glycosides are valuable organic compounds in the field of medicinal chemistry due to their ubiquity inside living systems and pronounced biological activity. Herein, we describe an approach to alkyl-ketones bearing glycal units via the Pd-catalyzed carbonylative coupling of 2-iodoglycals and alkyl and aryl halides. Examples bearing a variety of functional groups are presented as well as a mechanistic proposal for this transformation.