Ru/Rh-catalyzed Hydrogenation And Cycloisomerization

1.Rh-Catalyzed Asymmetric Hydrogenation of ?-Substituted Vinyl Sulfones:An Efficient Approach to Chiral SulfonesChiral sulfones represent an important functional group prevalently found in many biologically active compounds and pharmaceutical intermediates.Previous reported methods for the synthesis of chiral sulfones have included asymmetric arylations/alkenylations of ?-bromosulfones,Rhodium-and organo-catalyzed asymmetric conjugate addition to unsaturated sulfones,asymmetric radical additions,and asymmetric conjugate reduction of prochiral unsaturated sulfones.Catalytic asymmetric hydrogenation represents one of the most efficient,straightforward,and well-established approaches to chiral compounds.To date,only a few examples of asymmetric hydrogenation of unsaturated sulfones have been reported.Herein,we have developed an efficient strategy for highly enantioselective synthesis of ?-substituted chiral sulfones by Rh-catalyst asymmetric hydrogenation.This reaction features high reaction activity(>90% yield),high enantioselectivity(up to 99% ee),wide substrate scope,mild reaction conditions,and simple operation.It can be served as a practical way for synthesizing of chiral sulfones.2.Rhodium-Catalyzed Highly Regio-and Enantioselective Hydrogenation of Tetrasubstituted Allenyl SulfonesRegio-and enantio-controlled reduction of conjugated unsaturated bonds is a fundamental,yet challenging target in modern organic synthesis.Up to date,great efforts have been devoted towards addressing this issue and some important progress have been made.However,compared to the wide success in the regioselective asymmetic hydrogenation of various conjugated alkenes/ketones,the regio-and enantio-selective hydrogenation of allenes is rarely reported,despite the fact that the asymmetric semireduction of allenes provides an efficient access to chiral allylic compounds.The main reason could be the difficulty to simultaneously control the chemo-,regio-,and stereo-selectivity of this reaction.Moreover,this transformation might be further challenged by the typical regioselectivity leading to internal alkenes or inevitably forming completely reduced products.A highly regio-and enantio-selective hydrogenation of challenging tetrasubstituted allenyl sulfones has been developed,affording chiral allylic sulfones in good yields with excellent regio-and enantio-selectivities(up to 99% yield and 99% ee).This method provides an efficient and concise route to chiral allylic sulfones,thus offering an atom-economic process with a wide range of potential applications in organic synthesis and medicinal chemistry.3.Ru-Ctalyzed Hydrogenation of Simple AmidesThe reduction of carboxylic-acid derivatives plays an important role in organic synthesis.In particular,finding simple amides with a less electrophilic carbonyl group remains one of the major targets in the reduction of carboxylic-acid derivatives.Therefore,considerable efforts have been devoted to the development of efficient catalytic systems for the hydrogenation of amides with molecular hydrogen.Amides are known to be thermodynamically highly stable carboxylic acid derivatives,and the hydrogenation of amides can lead to either the amine or the alcohol.In the first reduction step,the corresponding hemiaminal is formed by a formal addition of molecular hydrogen to the carbonyl group of the amide.This hemiaminal is in equilibrium with the imine(via dehydration)or the corresponding aldehyde,depending on the reaction conditions.Subsequently,catalytic hydrogenation of the imine or the aldehyde leads to the amine or alcohol,respectively.Herein,a highly chemoselective and reactive direct catalytic reduction of various amides to amines and alcohols was developed by using a tetradentate ruthenium complex.The catalytic system showed excellent activity(turnover numbers up to 19600)and great functional group tolerance under mild reaction conditions,compared to several bidentate and tridentate ruthenium-catalyzed systems.4.Rh-Catalyzed Cycloisomerization of 1,6-AllenynesA pre-eminent goal of synthetic chemistry is the highly selective construction of targeted structural complexity in an atom-and step-economy fashion.Transition metal-catalyzed cycloisomerization reactions of 1,n-allenynes provide a powerful synthetic approach in this regard,as they facilitate the rapid assembly of complex polycyclic skeletons from simple linear substrates.Nevertheless,there are no reports of the asymmetric version of these reactions.Herein,we report an enantioselective Rh-catalyzed cycloisomerization of 1,6-allenynes to provide the proximal product 5/6-fused bicycle [4.3.0] nonadienes in good yields and with excellent enantioselectivities.Remarkably,this chemistry works perfectly for 1,6-allenynes having a cyclic substituent within the allene component,thereby affording synthetically formidable tricyclic products with excellent enantioselectivities.