The significance of axial chiral compounds in asymmetric organic catalysis,functional materials,and pharmaceutical useful molecules has encouraged advancements in the atroposelective synthesis of such compounds.Herein...The significance of axial chiral compounds in asymmetric organic catalysis,functional materials,and pharmaceutical useful molecules has encouraged advancements in the atroposelective synthesis of such compounds.Herein,we report the first atroposelective construction of axially chiral N-aryl benzimidazoles catalyzed by a polymer-supported chiral phosphoric acid.A varied library of atropisomers has been synthesized in 30%-96%yield with 58%-98%enantiomeric excess(ee)under a straightforward reaction setup(without the use of molecular sieves).Notably,even after 12 cycles,the immobilized catalyst maintained its reactivity and selectivity(TON>540).展开更多
Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In c...Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.展开更多
The first catalytic atroposelective synthesis of indole derivatives bearing N-N/C-C diaxes has been established by the strategy of de novo ring formation.By this strategy,various indolyl quinazolinones bearing vicinal...The first catalytic atroposelective synthesis of indole derivatives bearing N-N/C-C diaxes has been established by the strategy of de novo ring formation.By this strategy,various indolyl quinazolinones bearing vicinal N-N/C-C diaxes were synthesized in high yields with overall good diastereoselectivities and excellent enantioselectivities via chiral phosphoric acid-catalyzed onepot asymmetric formal(5+1)cycloaddition/oxidation reaction.Moreover,such indolyl quinazolinones bearing vicinal N-N/CC diaxes have good configurational stability and could be converted into new chiral ligands with applications in asymmetric catalysis.Therefore,this work not only offered a new member for the family of diaxial atropisomers,but also provided a powerful strategy for catalytic asymmetric synthesis of atropisomers bearing N-N/C-C diaxes.展开更多
Indole-based atropisomers are a very important class of axially chiral compounds.However,the atroposelective synthesis of axially chiral 2-arylindole remains largely unexplored.In this study,we report the successful s...Indole-based atropisomers are a very important class of axially chiral compounds.However,the atroposelective synthesis of axially chiral 2-arylindole remains largely unexplored.In this study,we report the successful synthesis of atropisomeric 2-arylindoles using direct amination of indoles with p-quinonediimines in the presence of chiral phosphoric acid as a catalyst.Quinonediimine acts as an aminating reagent through formal polarity inversion of imine.The malonate group on the 2-aryl of 2-indoles was found to be essen-tial for high enantioselectivity of the products.This could be due to the additional interaction between the ester group and the cata-lyst,as well as the intramolecular hydrogen bonding.Our findings provide a new strategy for the asymmetric construction of 2-arylindole atropisomers.展开更多
Indole and its derivatives represent the most important heterocycles that are widely present in bioactive molecules,natural products and advanced materials,and thus functionalization of simple indoles to construct com...Indole and its derivatives represent the most important heterocycles that are widely present in bioactive molecules,natural products and advanced materials,and thus functionalization of simple indoles to construct complex indole derivatives is a research area of great current interest.2,3-Difunctionalization of indoles has been extensively studied,but the reported examples are limited to the synthesis of 2,3-disubstituted indole derivatives or dearomatized products containing central chirality.Until now,atroposelective 2,3-difunctionalization of simple indoles for the synthesis of axially chiral molecules is unknown.In this article,we report a straightforward and general strategy for atroposelective 2,3-difunctionalization of simple indoles,forming indole-containing axially chiral products in good yields and excellent enantioselectivities.The strategy we introduce herein may lead to the discovery of new approaches for multifunctionalization of indoles and other heterocyclic scaffolds,thus accessing novel axially chiral heteroarene-containing scaffolds that may find applications in medicinal chemistry and asymmetric catalysis.展开更多
(Z)-7-Aryl-5-acyldibenzo[e,g][1,4]diazocin-6(5H)-one,a unique saddle-shaped bridged biaryl containing synchronized aryl–aryl and N-aryl stereogenic axes,was constructed for the first time in good yields with up to 96...(Z)-7-Aryl-5-acyldibenzo[e,g][1,4]diazocin-6(5H)-one,a unique saddle-shaped bridged biaryl containing synchronized aryl–aryl and N-aryl stereogenic axes,was constructed for the first time in good yields with up to 96%enantiomeric excess(ee).The threecomponent coupling reaction,involving aryl iodide,2,2′-diisocyano-1,1′-biphenyl,and carboxylate,constructs the eight-membered ring in an atroposelective manner through palladium-catalyzed double isocyanide insertion followed by C–Obond formation during reductive elimination and amide formation after acyl transfer.展开更多
Axially chiral molecules have been widely used in inorganic,material and medicinal chemistry.Compared with well-established N-heterocyclic carbene(NHC)-catalyzed asymmetric construction of centrally chiral molecules,N...Axially chiral molecules have been widely used in inorganic,material and medicinal chemistry.Compared with well-established N-heterocyclic carbene(NHC)-catalyzed asymmetric construction of centrally chiral molecules,NHC-catalyzed atroposelective synthesis of axially chiral molecules remains largely underdeveloped.Notably,alkynyl acyl azolium intermediates were commonly used in constructing a heteroaryl ring to furnish axially enantioenriched heteroaryl-aryls.The inherent character of the intermediates often led to react with sterically hindered substrates difficultly.Herein,we have successfully disclosed the atroposelective synthesis of axially chiral heteroaryl-aryls from sterically hindered enols through the use of chiral NHCs as catalysts for highly enantioselective Coates-Claisen rearrangements via catalytically generatedα,β-unsaturated acyl azoliums.This approach will enable the concise synthesis of valuable tetra-ortho-substituted 2-pyrones in one step with good yield and chirality control.展开更多
An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides,aryliodides,and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using ...An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides,aryliodides,and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using an enantiopure norbornene derivative as the chiral mediator.A broad range of atropisomeric biaryl-based monophosphine oxides were obtained in good efficiency with excellent enantioselectivity.展开更多
The catalytic atroposelective synthesis of axially chiral isochromenone-indoles has been established by the strategy of designing homophthalic anhydride-based indole derivatives as a new type of indole-based platform ...The catalytic atroposelective synthesis of axially chiral isochromenone-indoles has been established by the strategy of designing homophthalic anhydride-based indole derivatives as a new type of indole-based platform molecules for dynamic kinetic resolution.By this strategy,a wide range of axially chiral isochromenone-indoles were synthesized in high yields with excellent enantioselectivities(up to 98%yield,97%ee)via the catalytic asymmetric sulfonylation reaction of homophthalic anhydridebased indole derivatives with aryl sulfonyl chlorides under the catalysis of chiral quaternary ammonium salt as a phase-transfer catalyst.展开更多
Comprehensive Summary A new strategy for the enantioselective synthesis of axially chiral 3,3'-bisindoles was devised by the direct coupling of two indole rings.This strategy makes use of the C3-umpolung reactivit...Comprehensive Summary A new strategy for the enantioselective synthesis of axially chiral 3,3'-bisindoles was devised by the direct coupling of two indole rings.This strategy makes use of the C3-umpolung reactivity of 2-indolylmethanols,which enables the catalytic asymmetric addition reaction of 2-indolylmethanols with rationally designed 2-substituted indoles,thus constructing axially chiral 3,3'-bisindole scaffolds in overall excellent yields(up to 98%)with high enantioselectivities(up to 96:4 er).This approach not only has overcome the challenges in constructing axially chiral five-five-membered heterobiaryls,but also represents a new application of the C3-umpolung reactivity of 2-indolylmethanols in asymmetric catalysis.More importantly,this class of axially chiral 3,3'-bisindoles can undergo a variety of post-functionalizations to give axially chiral 3,3'-bisindole-based organocatalysts,which have found their preliminary applications in asymmetric catalysis.展开更多
The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area of research due to the unique characteristics of such frameworks.Nevertheless,research in this area is still in its ...The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area of research due to the unique characteristics of such frameworks.Nevertheless,research in this area is still in its infancy and has some challenges,such as designing and constructing new classes of axially chiral indole-based scaffolds and developing their applications in chiral catalysts,ligands,etc.To overcome these challenges,we present herein the design and atroposelective synthesis of aryl-pyrroloindoles as a new class of axially chiral indole-based scaffolds via the strategy of organocatalytic asymmetric(2+3)cyclization between 3-arylindoles and propargylic alcohols.More importantly,this new class of axially chiral scaffolds was derived into phosphines,which served as efficient chiral ligands in palladium-catalyzed asymmetric reactions.Moreover,theoretical calculations provided an in-depth understanding of the reaction mechanism.This work offers a new strategy for constructing axially chiral indole-based scaffolds,which are promising for finding more applications in asymmetric catalysis.展开更多
A highly efficient enantioselective construction of heterobiaryl N-oxides was developed.A series of axially chiral heterobiaryl N-oxides were generated via the cascade reaction of aminobenzamides with heterobiaryl ald...A highly efficient enantioselective construction of heterobiaryl N-oxides was developed.A series of axially chiral heterobiaryl N-oxides were generated via the cascade reaction of aminobenzamides with heterobiaryl aldehydes in the presence of chiral phosphoric acids.A number of atropisomers were afforded in moderate to good yields with excellent enantioselectivities and diastereoselectivities.Preliminary results demonstrate that the heterobiaryl N-oxides can be utilized as efficient chiral ligands in asymmetric catalysis.展开更多
An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of alkyne via vinylidene...An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of alkyne via vinylidene ortho-quinone methides(VQMs).The methodology reported herein was characterized by rapid reactions(most completed in seconds),high stereocontrol(up to 98%ee),and broad substrate scope(60 examples of different skeletal types,stereogenicelements,andring sizes).展开更多
The merging of C-H and C-C bond cleavage into one single chemical process remains a daunting challenge,especially in an asymmetric manner.Herein,a Pd(Ⅱ)-catalyzed enantioselective tandem C-H/C-C activation for the sy...The merging of C-H and C-C bond cleavage into one single chemical process remains a daunting challenge,especially in an asymmetric manner.Herein,a Pd(Ⅱ)-catalyzed enantioselective tandem C-H/C-C activation for the synthesis of axially chiral biaryls is described.Two types of simple cyclopropanes,such as vinylcyclopropanes and cyclopropanols,were used as efficient and readily available coupling partners.展开更多
基金supported by Shenzhen Science and Technology Research(Nos.JSGG20201103153807021,GXWD20220811173736002,KCXFZ20230731094904009)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.24qnpy060)+2 种基金Natural Science Foundation of Guangdong Province(No.2021A1515110366)National Natural Science Foundation of China(Nos.22302048,82204231,22275146)Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application。
文摘The significance of axial chiral compounds in asymmetric organic catalysis,functional materials,and pharmaceutical useful molecules has encouraged advancements in the atroposelective synthesis of such compounds.Herein,we report the first atroposelective construction of axially chiral N-aryl benzimidazoles catalyzed by a polymer-supported chiral phosphoric acid.A varied library of atropisomers has been synthesized in 30%-96%yield with 58%-98%enantiomeric excess(ee)under a straightforward reaction setup(without the use of molecular sieves).Notably,even after 12 cycles,the immobilized catalyst maintained its reactivity and selectivity(TON>540).
基金supported by the National Key Research and Development Program of China(2023YFA1507500)the National Natural Science Foundation of China(22171260,92356302)+1 种基金the Natural Science Foundation of Liaoning Province(2023-MS-009)the Dalian Institute of Chemical Physics(DICP I202442)。
文摘Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.
基金supported by the National Natural Science Foundation of China(22125104,22101103,22401115)the Natural Science Foundation of Jiangsu Province(BK20240052)the Project for Excellent Scientific and Technological Innovation Team of Jiangsu Province。
文摘The first catalytic atroposelective synthesis of indole derivatives bearing N-N/C-C diaxes has been established by the strategy of de novo ring formation.By this strategy,various indolyl quinazolinones bearing vicinal N-N/C-C diaxes were synthesized in high yields with overall good diastereoselectivities and excellent enantioselectivities via chiral phosphoric acid-catalyzed onepot asymmetric formal(5+1)cycloaddition/oxidation reaction.Moreover,such indolyl quinazolinones bearing vicinal N-N/CC diaxes have good configurational stability and could be converted into new chiral ligands with applications in asymmetric catalysis.Therefore,this work not only offered a new member for the family of diaxial atropisomers,but also provided a powerful strategy for catalytic asymmetric synthesis of atropisomers bearing N-N/C-C diaxes.
基金support from the National Key R&D Program of China (2022YFA1503703,2021YFF0701604)the National Natural Science Foundation of China (21825105,22231004,22271135)+1 种基金Guangdong Innovative Program (2019BT02Y335)Shenzhen Science and Technology Program (KQTD20210811090112004,JCYJ20210324120205016,JCYJ20210324105005015).
文摘Indole-based atropisomers are a very important class of axially chiral compounds.However,the atroposelective synthesis of axially chiral 2-arylindole remains largely unexplored.In this study,we report the successful synthesis of atropisomeric 2-arylindoles using direct amination of indoles with p-quinonediimines in the presence of chiral phosphoric acid as a catalyst.Quinonediimine acts as an aminating reagent through formal polarity inversion of imine.The malonate group on the 2-aryl of 2-indoles was found to be essen-tial for high enantioselectivity of the products.This could be due to the additional interaction between the ester group and the cata-lyst,as well as the intramolecular hydrogen bonding.Our findings provide a new strategy for the asymmetric construction of 2-arylindole atropisomers.
文摘Indole and its derivatives represent the most important heterocycles that are widely present in bioactive molecules,natural products and advanced materials,and thus functionalization of simple indoles to construct complex indole derivatives is a research area of great current interest.2,3-Difunctionalization of indoles has been extensively studied,but the reported examples are limited to the synthesis of 2,3-disubstituted indole derivatives or dearomatized products containing central chirality.Until now,atroposelective 2,3-difunctionalization of simple indoles for the synthesis of axially chiral molecules is unknown.In this article,we report a straightforward and general strategy for atroposelective 2,3-difunctionalization of simple indoles,forming indole-containing axially chiral products in good yields and excellent enantioselectivities.The strategy we introduce herein may lead to the discovery of new approaches for multifunctionalization of indoles and other heterocyclic scaffolds,thus accessing novel axially chiral heteroarene-containing scaffolds that may find applications in medicinal chemistry and asymmetric catalysis.
基金the National Natural Science Foundation of China(nos.21772198,21871268,and 22071250)the Frontier Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(no.2018GRZ110105017)+2 种基金the Natural Science Foundation of Guangdong Province of China(no.2020A1515011428)the“BAGUI Scholar”Program of Guangxi Province of China,and SKLRD Open Project(no.SKLRD-Z-202014)for financial supportthe Guangzhou Branch of the Supercomputing Center of CAS for support.
文摘(Z)-7-Aryl-5-acyldibenzo[e,g][1,4]diazocin-6(5H)-one,a unique saddle-shaped bridged biaryl containing synchronized aryl–aryl and N-aryl stereogenic axes,was constructed for the first time in good yields with up to 96%enantiomeric excess(ee).The threecomponent coupling reaction,involving aryl iodide,2,2′-diisocyano-1,1′-biphenyl,and carboxylate,constructs the eight-membered ring in an atroposelective manner through palladium-catalyzed double isocyanide insertion followed by C–Obond formation during reductive elimination and amide formation after acyl transfer.
基金supported by the National Key R&D Program of China (2017YFA0204704)the National Natural Science Foundation of China (21602105)+2 种基金the General Program of Chongqing Natural Science(cstc2020jcyj-msxmX0712)Ningbo Natural Science Foundation (202003N4063)the Natural Science Foundation of Jiangsu Province (BK20221309)
文摘Axially chiral molecules have been widely used in inorganic,material and medicinal chemistry.Compared with well-established N-heterocyclic carbene(NHC)-catalyzed asymmetric construction of centrally chiral molecules,NHC-catalyzed atroposelective synthesis of axially chiral molecules remains largely underdeveloped.Notably,alkynyl acyl azolium intermediates were commonly used in constructing a heteroaryl ring to furnish axially enantioenriched heteroaryl-aryls.The inherent character of the intermediates often led to react with sterically hindered substrates difficultly.Herein,we have successfully disclosed the atroposelective synthesis of axially chiral heteroaryl-aryls from sterically hindered enols through the use of chiral NHCs as catalysts for highly enantioselective Coates-Claisen rearrangements via catalytically generatedα,β-unsaturated acyl azoliums.This approach will enable the concise synthesis of valuable tetra-ortho-substituted 2-pyrones in one step with good yield and chirality control.
基金Financial support from National Natural Science Foundation of China(nos.21772046 and 2193103)is gratefully acknowledged.
文摘An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides,aryliodides,and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using an enantiopure norbornene derivative as the chiral mediator.A broad range of atropisomeric biaryl-based monophosphine oxides were obtained in good efficiency with excellent enantioselectivity.
基金supported by the National Science Foundation of China(22125104,21831007,22101103)the Natural Science Foundation of Jiangsu Province(BK20201018)
文摘The catalytic atroposelective synthesis of axially chiral isochromenone-indoles has been established by the strategy of designing homophthalic anhydride-based indole derivatives as a new type of indole-based platform molecules for dynamic kinetic resolution.By this strategy,a wide range of axially chiral isochromenone-indoles were synthesized in high yields with excellent enantioselectivities(up to 98%yield,97%ee)via the catalytic asymmetric sulfonylation reaction of homophthalic anhydridebased indole derivatives with aryl sulfonyl chlorides under the catalysis of chiral quaternary ammonium salt as a phase-transfer catalyst.
基金supported by NSFC(22125104,21831007 and 22101103)the Natural Science Foundation of Jiangsu Province(BK20201018)the Natural Science Foundation of Xuzhou City(KC21021).
文摘Comprehensive Summary A new strategy for the enantioselective synthesis of axially chiral 3,3'-bisindoles was devised by the direct coupling of two indole rings.This strategy makes use of the C3-umpolung reactivity of 2-indolylmethanols,which enables the catalytic asymmetric addition reaction of 2-indolylmethanols with rationally designed 2-substituted indoles,thus constructing axially chiral 3,3'-bisindole scaffolds in overall excellent yields(up to 98%)with high enantioselectivities(up to 96:4 er).This approach not only has overcome the challenges in constructing axially chiral five-five-membered heterobiaryls,but also represents a new application of the C3-umpolung reactivity of 2-indolylmethanols in asymmetric catalysis.More importantly,this class of axially chiral 3,3'-bisindoles can undergo a variety of post-functionalizations to give axially chiral 3,3'-bisindole-based organocatalysts,which have found their preliminary applications in asymmetric catalysis.
基金support from the National Natural Science Foundation of China (22125104 and 21831007)Natural Science Foundation of Jiangsu Province (BK20210916)High Education Natural Science Foundation of Jiangsu Province (21KJB150009).
文摘The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area of research due to the unique characteristics of such frameworks.Nevertheless,research in this area is still in its infancy and has some challenges,such as designing and constructing new classes of axially chiral indole-based scaffolds and developing their applications in chiral catalysts,ligands,etc.To overcome these challenges,we present herein the design and atroposelective synthesis of aryl-pyrroloindoles as a new class of axially chiral indole-based scaffolds via the strategy of organocatalytic asymmetric(2+3)cyclization between 3-arylindoles and propargylic alcohols.More importantly,this new class of axially chiral scaffolds was derived into phosphines,which served as efficient chiral ligands in palladium-catalyzed asymmetric reactions.Moreover,theoretical calculations provided an in-depth understanding of the reaction mechanism.This work offers a new strategy for constructing axially chiral indole-based scaffolds,which are promising for finding more applications in asymmetric catalysis.
基金supported by the National Natural Science Foundation of China(21871160,21672121,22071130)the fellowship of Tsinghua-Peking Centre for Life Sciences(CLS).
文摘A highly efficient enantioselective construction of heterobiaryl N-oxides was developed.A series of axially chiral heterobiaryl N-oxides were generated via the cascade reaction of aminobenzamides with heterobiaryl aldehydes in the presence of chiral phosphoric acids.A number of atropisomers were afforded in moderate to good yields with excellent enantioselectivities and diastereoselectivities.Preliminary results demonstrate that the heterobiaryl N-oxides can be utilized as efficient chiral ligands in asymmetric catalysis.
基金provided by the Zhejiang Provincial Natural Science Foundation of China(grant no.LQ19B020003)the Scientific Research Foundation of China(grant nos.21922101,21772018,and 21901026)the Fundamental Research Funds for the Central Universities(project no.2020CQJQY-Z002).
文摘An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of alkyne via vinylidene ortho-quinone methides(VQMs).The methodology reported herein was characterized by rapid reactions(most completed in seconds),high stereocontrol(up to 98%ee),and broad substrate scope(60 examples of different skeletal types,stereogenicelements,andring sizes).
基金The authors gratefully acknowledge financial support from the NSFC(nos.21772170 and 21925109 for B.-F.S.and no.21901228 for G.L.)Outstanding Young Talents of Zhejiang Province High-level Personnel of Special Support(no.ZJWR0108 for B.-F.S.).
文摘The merging of C-H and C-C bond cleavage into one single chemical process remains a daunting challenge,especially in an asymmetric manner.Herein,a Pd(Ⅱ)-catalyzed enantioselective tandem C-H/C-C activation for the synthesis of axially chiral biaryls is described.Two types of simple cyclopropanes,such as vinylcyclopropanes and cyclopropanols,were used as efficient and readily available coupling partners.
