A new class of axially chiral styrene-based thiourea-tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements and multiple activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo-, diastereo- and enantioselective (2+4) cyclization of 2-benzothiazolimines with homophthalic anhydrides in good yields (up to 96%) with excellent stereoselectivities (all >95:5 dr, up to 98% ee). More importantly, theoretical calculations elucidated the important role of axially chiral styrene moiety in controlling both the reactivity and the enantioselectivity. This work not only represents the first design of styrene-based chiral thiourea-tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2-benzothiazolimines, but also gives an in-depth understanding of axially chiral styrene-based organocatalysts.
https://ift.tt/3xH2jO8
I drew out both structures and I can't see how 3-hydroxyl-3-methylcycloheptanone (bottom) could be neither the thermodynamic or kinetic product when only 2 possible products are formed. If there was a third possible product, then I suppose it could be both less stable than the thermodynamic and slower to form than the kinetic (i.e. then it would be neither), but in this context, I don't see how this could be true?
https://preview.redd.it/hwpkxgd2txg71.jpg?width=611&format=pjpg&auto=webp&s=1584270056f1a0d5ce344fa6f742163cfbc8880d
A range of functionalized organomagnesium halides and enol lactones underwent rhenium-catalyzed sequential arylation–acyl cyclization under mild reaction conditions, thus providing an expedient route to polyfunctionalized indenones with complete control of regioselectivity. This approach features a broad substrate scope, excellent functional group tolerance, and synthetic utility in the straightforward synthesis of biologically relevant molecules.
Abstract
A set of rhenium-catalyzed arylation–acyl cyclizations between (hetero)arylmagnesium halides and enol lactones through a cascade C(sp2)−C(sp2)/C(sp2)−C(sp2) bond formation under mild reaction conditions has been developed. Indeed, a wide range of functional groups on both organomagnesium halides and enol lactones is well tolerated by the simple rhenium catalysis, thus furnishing polyfunctionalized indenones in one-pot fashion and with complete control of the regioselectivity. Moreover, this approach also provides a straightforward synthetic route to neolignan and (iso)pauciflorol F. Mechanistic studies demonstrated that the reaction involves a sequence of syn-carborhenation and intramolecular nucleophilic addition.
https://ift.tt/3vw4Ubl
I'm trying to cyclize N-phenethylacetamide to form the corresponding dihydroisoquinoline and this procedure I'm following calls for polyphosphoric acid. Is there any advantage to using polyphosphoric acid over a reagent like POCl3? I'm having a hard time ordering polyphosphoric acid so am considering other reagents.
The quinazolinone motif is an important feature in natural products and drug candidates although enantioselective approaches to such scaffolds remain rare. An enantioselective Cu-catalyzed borylative cyclization delivers pyrroloquinazolines, featuring quaternary stereocenters and synthetic handles for further derivatization, with high enantio- and diastereocontrol.
Abstract
Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper-catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone motifs. The reaction proceeds with high enantio- and diastereocontrol, and can deliver products containing quaternary stereocenters. The utility of the products is demonstrated through further manipulations.
https://ift.tt/3uZP6O2
I've seen this in several organic chemistry synthesis papers...
One paper for example is "Synthesis of Enantiomerically Pure 5-Substituted-Piperazine-2-Acetic Acid Esters as Intermediates for Library Production" by Prashi Jain et al. (2019)
I tried to search for it... I'll check my textbooks and see I suppose...
Enantioselective cobalt‐catalyzed hydrosilylation/cyclization of 1,6‐enynes is developed to access synthetically versatile chiral alkylsilanes with a catalyst generated in situ from Co(acac)2 and (R,Sp)‐Josiphos. A wide range of 1,6‐enynes react to afford the corresponding alkylsilanes in good yields with excellent enantioselectivity (up to >99 % ee).
Abstract
We report an enantioselective cobalt‐catalyzed hydrosilylation/cyclization reaction of 1,6‐enynes with secondary and tertiary hydrosilanes employing a catalyst generated in situ from the combination of Co(acac)2 and (R,Sp )‐Josiphos. A wide range of oxygen‐, nitrogen‐, and carbon‐tethered 1,6‐enynes reacted with Ph2SiH2, (EtO)3SiH, or (RO)2MeSiH to afford the corresponding chiral organosilane products in high yields and up to >99 % ee. This cobalt‐catalyzed hydrosilylation/cyclization also occurred with prochiral secondary hydrosilane PhMeSiH2 to yield chiral alkylsilanes containing both carbon‐ and silicon‐stereogenic centers with excellent enantioselectivity, albeit with modest diastereoselectivity. The chiral organosilane products from this cobalt‐catalyzed asymmetric hydrosilylation/cyclization could be converted to a variety of chiral five‐membered heterocyclic compounds by stereospecific conversion of their C−Si and Si−H bonds without loss of enantiopurity.
https://ift.tt/3xd9ooG
So this is an issue i have in lab right now, which is going to be kept broad as it is active research and my advisor does not approve of the use of internet for help.
I generate a reactive intermediate that can do one of two things:
-
rearranges giving stable product a
-
undergo cyclization with another species present giving stable products b and c in an unknown proportion based on the two geometry possibilities for the 3+2 cycloaddition.
Right now I am getting a mix of products a + b + c, and am wondering if there is a way to favor the cycloaddition vs the rearrangement?
Should I be hitting solvent screening or temperature first to try to shift one way or the other?
Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c01194
Jin Cao, Meng-Yang Hu, Si-Yuan Liu, Xin-Yu Zhang, Shou-Fei Zhu, and Qi-Lin Zhou
https://ift.tt/3nwcTSH
Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c03394
Mengqing Chen, Wataru Sato, Rui Shang, and Eiichi Nakamura
https://ift.tt/2QKtJBt
A versatile direct cyclization is demonstrated to proceed by substituted diarylamines with various ketones under simple solvent‐free and metal‐free conditions. It shows huge potential in preparing spiro‐acridan derivatives and TADF emitters.
Abstract
Spiro‐acridan (SpA) derivatives possess a great potential in preparing efficient thermally activated delayed fluorescent (TADF) emitters. However, the conventional synthetic routes are cost‐expensive and time‐consuming. The development of a simple procedure to synthesize SpAs is still in urgent pursuing appreciated by academic and industrial communities. In this contribution, we present a feasible acid‐catalyzed solvent‐free metal‐free cyclization between diarylamines and ketones to construct SpAs. The as‐constructed moieties provide a wide possibility to assemble efficient TADF emitters. As an example, D2T‐TR with high photoluminescent quantum yield and proper TADF character is applied in organic light emitting diodes (OLEDs) which achieves a maximum external quantum efficiency (EQE) of 27.1 %. This work shows us a bright inspiration on developing excellent organic optoelectronic materials and an effective tool to realize it.
https://ift.tt/3d7ApRf
The development of efficient and sustainable methods to access saturated N ‐heterocycles is of great importance because of the prevalence of these structures in natural products and bioactive compounds. Pd‐catalyzed aza‐Wacker type cyclization is a powerful method and provide access to N ‐heterocycles bearing an alkene moiety available for further synthetic manipulations from readily available materials. Herein we disclose a catalyst‐ and reagent‐free formal aza‐Wacker type cyclization reaction for the synthesis of functionalized saturated N ‐heterocycles. Key to the success is to conduct the reactions in a continuous‐flow electrochemical reactor without adding supporting electrolyte or additives. The reactions are characterized by broad tolerance of di‐, tri‐ and tetrasubstituted alkenes.
https://ift.tt/38fzjRL
Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron‐deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible‐light (410 nm) irradiation, affording anti‐Markonikov hydroarylated compounds in up to 95% yield. Besides, a protocol for [Pt(O^N^C^N)]‐catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4‐dihydroquinolinones has been developed.
https://ift.tt/3no2at8
Hey everyone!
Thank you again for all the support this community has shown for my new youtube channel about advances in synthetic organic chemistry - your positivity has really helped keep the content coming during the current pandemic and I really appreciate it. This week's episode focuses on the Nazarov cyclization! https://youtu.be/nfoBunOTkVk
Stay safe!
Both right‐ and left‐handed helical spiro‐conjugated ladder polymers were successfully synthesized through quantitative and chemoselective acid‐promoted intramolecular alkyne benzannulations of random‐coil precursor polymers containing optically‐active 1,1′‐spirobiindane units as a spiro‐type chiral linkage in the main chain that relies on the 2,6‐dimethyl substituents introduced to the 4‐alkoxyphenylethynyl pendants.
Abstract
We report the unprecedented synthesis of one‐handed helical spiro‐conjugated ladder polymers with well‐defined primary and secondary structures, in which the spiro‐linked dibenzo[a,h]anthracene fluorophores are arranged in a one‐handed twisting direction, through quantitative and chemoselective acid‐promoted intramolecular cyclizations of random‐coil precursor polymers composed of chiral 1,1′‐spirobiindane and achiral bis[2‐(4‐alkoxyphenyl)ethynyl]phenylene units. Intense circular dichroism (CD) and circularly polarized luminescence (CPL) were observed, whereas the precursor polymers exhibited negligible CD and CPL activities. The introduction of 2,6‐dimethyl substituents on the 4‐alkoxyphenylethynyl pendants is of key importance for this simple, quantitative, and chemoselective cyclization. This strategy is applicable to the defect‐free precise synthesis of other varieties of fully π‐conjugated molecules and coplanar ladder polymers that have not been achieved before.
https://ift.tt/3bEF9y9
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c12659
Huangtianzhi Zhu, Irene Badía-Domínguez, Bingbing Shi, Qi Li, Peifa Wei, Hao Xing, M. Carmen Ruiz Delgado, and Feihe Huang
https://ift.tt/39BGAv0
Metal‐catalyzed Hydrogen atom transfer: A radical cyclization initiated by metal‐catalyzed hydrogen atom transfer (MHAT) was used to construct the cis‐decalin framework, further leading to the asymmetric synthesis of dankasterones A and B and periconiastone. Interconversion of dankasterone B and periconiastone A was observed.
Abstract
We describe herein the assembly of the cis‐decalin framework through radical cyclization initiated by metal‐catalyzed hydrogen atom transfer (MHAT), further applied it in the asymmetric synthesis of dankasterones A and B and periconiastone A. Position‐selective C−H oxygenation allowed for installation of the necessary functionality. A radical rearrangement was adopted to create 13(14→8)abeo‐8‐ergostane skeleton. Interconversion of dankasterone B and periconiastone A was realized through biomimetic intramolecular aldol and retro‐aldol reactions. The MHAT‐based approach, serves as a new dissection means, is complementary to the conventional ways to establish cis‐decalin framework.
https://ift.tt/2Kocjan
Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c00640
Fan Teng, Ting Yu, Yan Peng, Weiming Hu, Huaanzi Hu, Yimiao He, Shuang Luo, and Qiang Zhu
https://ift.tt/3jDTwoT
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c07918
https://ift.tt/3hXTS8m
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c10055
Zhengtian Ding, Yiming Wang, Wenfeng Liu, Yate Chen, and Wangqing Kong
https://ift.tt/3hfmUAA
1,1,2‐Trifunctionalization of terminal alkynes is achieved by a radical cascade reaction comprising an addition, translocation, cyclization, and trapping step. Substituted cylopentanes bearing the medicinally relevant CF3‐group along with the synthetically valuable alkynyl moiety are obtained. The method uses readily prepared alkynyl triflones as CF3‐radical precursors and as alkynylating reagents.
Abstract
Radical 1,1,2‐trifunctionalization of terminal alkynes by an addition–translocation–cyclization–trapping sequence using readily available alkynyl triflones as trifluoromethyl radical precursors and trapping reagents is reported. Cascades occur by addition of the trifluoromethyl radical to a terminal alkyne, 1,5‐hydrogen atom transfer, 5‐exo‐cyclization, and subsequent alkynylation to provide (1‐trifluoromethyl)propargyl cyclopentanes. Reactions proceed with commercial dibenzoyl peroxide or α,α′‐azobisisobutyronitrile as the initiator at elevated temperature and provide the highly substituted cyclopentanes in good yields.
https://ift.tt/3d9PIsd
A chiral diene‐rhodium complex was found to catalyze the reaction of 1,6‐enynes with ArZnCl to give high yields of 2‐(alkylidene)cyclopentylmethylzincs with high enantioselectivity (95–99 % ee). The enantioenriched alkylzincs were readily converted in a one‐pot approach into a wide variety of functionalized products by taking advantage of their unique reactivity.
Abstract
A chiral diene‐rhodium complex was found to catalyze the reaction of 1,6‐enynes with ArZnCl to give high yields of 2‐(alkylidene)cyclopentylmethylzincs with high enantioselectivity (95–99 % ee). The enantioenriched alkylzincs were readily converted in a one‐pot approach into a wide variety of functionalized products by taking advantage of their unique reactivity. The catalytic cylcle involves arylrhodation of alkyne, intramolecular alkenylrhodation of alkene, and transmetalation of the alkyl‐rhodium intermediate into alkylzinc.
https://ift.tt/32qtrTK
In my never ending quest for piperidine I've stumbled upon another route that may be accessible to me. The only cyclization synthesis I know of is succinic acid to succinimide, but maybe cadaverine will work the same way. Is there a way to pull off only one amine group on the chain, maybe by diazotization?
We report herein a nonbiomimetic strategy for the total synthesis of the plicamine‐type alkaloids, zephycarinatines C and D. The key feature of the synthesis was the stereoselective reductive radical ipso‐cyclization using visible‐light‐mediated photoredox catalysis. This cyclization enabled the construction of a 6,6‐spirocyclic core structure by the addition of the carbon‐centered radical onto the aromatic ring. The biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative having a keto group displayed moderate inhibitory activity against LPS‐induced NO production. This approach would offer future opportunities to expand the chemical diversity derived from plicamine‐type alkaloids as well as provide useful intermediates for their syntheses.
https://ift.tt/2DPDR4X
We report an enantioselective cobalt‐catalyzed hydrosilylation/cyclization reaction of 1,6‐enynes with secondary and tertiary hydrosilanes with a catalyst generated in situ from the combination of Co(acac) 2 and ( R , S p )‐Josiphos. Under identified conditions, a wide range of oxygen‐, nitrogen‐, and carbon‐tethered 1,6‐enynes reacted with Ph 2 SiH 2 , (EtO) 3 SiH, or (RO) 2 MeSiH to afford the corresponding chiral organosilane products in high yields with excellent enantioselectivity (up to >99% ee). In addition, this cobalt‐catalyzed hydrosilylation/cyclization also occurred with prochiral secondary hydrosilane PhMeSiH 2 to yield chiral alkylsilanes containing both carbon‐ and silicon‐stereogenic centers with excellent enantioselectivity, albeit with modest diastereoselectivity. The chiral organosilane products from this cobalt‐catalyzed asymmetric hydrosilylation/cyclization could be converted to a variety of chiral five‐membered heterocyclic compounds by stereospecific conversion of their C‐Si and Si‐H bonds without loss of enantiopurity. Mechanistic studies including deuterium‐labeling, control, and competition experiments suggest a chiral cobalt hydride intermediate [( L* )Co‐H], the chelation of 1,6‐enynes to cobalt catalysts, and the regioselectivity controlled by the relative reactivity of the alkyne and alkene moieties toward hydrocobaltation.
https://ift.tt/30qh3AR
Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper‐catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone motifs. The reaction proceeds with high enantio‐ and diastereocontrol, and can deliver products containing quaternary stereocenters. The utility of the products is demonstrated through further manipulations.
https://ift.tt/326U1A2
A continuous‐flow electrochemical aza‐Wacker‐type cyclization reaction that is free of catalyst, oxidant, supporting electrolyte, and additives is presented. The method is scalable and compatible with di‐, tri‐, and tetrasubstituted alkenes.
Abstract
The development of efficient and sustainable methods to access saturated N‐heterocycles is of great importance because of the prevalence of these structures in natural products and bioactive compounds. Pd‐catalyzed aza‐Wacker type cyclization is a powerful method and provides access to N‐heterocycles bearing an alkene moiety available for further synthetic manipulations from readily available materials. Herein we disclose a catalyst‐ and reagent‐free formal aza‐Wacker type cyclization reaction for the synthesis of functionalized saturated N‐heterocycles. Key to the success is to conduct the reactions in a continuous‐flow electrochemical reactor without adding supporting electrolyte or additives. The reactions are characterized by broad tolerance of di‐, tri‐ and tetrasubstituted alkenes.
https://ift.tt/3s0Szts
Enantioselective cobalt‐catalyzed hydrosilylation/cyclization of 1,6‐enynes is developed to access synthetically versatile chiral alkylsilanes with a catalyst generated in situ from Co(acac)2 and (R,Sp)‐Josiphos. A wide range of 1,6‐enynes react to afford the corresponding alkylsilanes in good yields with excellent enantioselectivity (up to >99 % ee).
Abstract
We report an enantioselective cobalt‐catalyzed hydrosilylation/cyclization reaction of 1,6‐enynes with secondary and tertiary hydrosilanes employing a catalyst generated in situ from the combination of Co(acac)2 and (R,Sp )‐Josiphos. A wide range of oxygen‐, nitrogen‐, and carbon‐tethered 1,6‐enynes reacted with Ph2SiH2, (EtO)3SiH, or (RO)2MeSiH to afford the corresponding chiral organosilane products in high yields and up to >99 % ee. This cobalt‐catalyzed hydrosilylation/cyclization also occurred with prochiral secondary hydrosilane PhMeSiH2 to yield chiral alkylsilanes containing both carbon‐ and silicon‐stereogenic centers with excellent enantioselectivity, albeit with modest diastereoselectivity. The chiral organosilane products from this cobalt‐catalyzed asymmetric hydrosilylation/cyclization could be converted to a variety of chiral five‐membered heterocyclic compounds by stereospecific conversion of their C−Si and Si−H bonds without loss of enantiopurity.
https://ift.tt/3xd9ooG
We report the unprecedented synthesis of one‐handed helical spiro‐conjugated ladder polymers with well‐defined primary and secondary structures, in which the spiro‐linked dibenzo[ a , h ]anthracene fluorophores are arranged in a one‐handed twisting direction, through quantitative and chemoselective acid‐promoted intramolecular cyclizations of random‐coil precursor polymers composed of chiral 1,1’‐spirobiindane and achiral bis[2‐(4‐alkoxyphenyl)ethynyl]phenylene units. Intense circular dichroism (CD) and circularly polarized luminescence (CPL) were observed, whereas the precursor polymers exhibited negligible CD and CPL activities. The introduction of 2,6‐dimethyl substituents on the 4‐alkoxyphenylethynyl pendants is of key importance for this simple, quantitative, and chemoselective cyclization. This strategy is applicable to the defect‐free precise synthesis of other varieties of fully π‐conjugated molecules and coplanar ladder polymers that have not been achieved before.
https://ift.tt/3bEF9y9
We describe herein the assembly of the cis ‐decalin framework through radical cyclization initiated by metal‐catalyzed hydrogen atom transfer (MHAT), further applied it in the asymmetric synthesis of dankasterones A and B and periconiastone A. Position‐selective C−H oxygenation allowed for installation of the necessary functionality. A radical rearrangement was adopted to create 13(14→8) abeo ‐8‐ergostane skeleton. Interconversion of dankasterone B and periconiastone A was realized through biomimetic intramolecular aldol and retro‐aldol reactions. The MHAT‐based approach, serves as a new dissection means, is complementary to the conventional ways to establish cis ‐decalin framework.
https://ift.tt/2Kocjan
1,1,2‐Trifunctionalization of terminal alkynes is achieved by a radical cascade reaction comprising an addition, translocation, cyclization, and trapping step. Substituted cylopentanes bearing the medicinally relevant CF3‐group along with the synthetically valuable alkynyl moiety are obtained. The method uses readily prepared alkynyl triflones as CF3‐radical precursors and as alkynylating reagents.
Abstract
Radical 1,1,2‐trifunctionalization of terminal alkynes by an addition–translocation–cyclization–trapping sequence using readily available alkynyl triflones as trifluoromethyl radical precursors and trapping reagents is reported. Cascades occur by addition of the trifluoromethyl radical to a terminal alkyne, 1,5‐hydrogen atom transfer, 5‐exo‐cyclization, and subsequent alkynylation to provide (1‐trifluoromethyl)propargyl cyclopentanes. Reactions proceed with commercial dibenzoyl peroxide or α,α′‐azobisisobutyronitrile as the initiator at elevated temperature and provide the highly substituted cyclopentanes in good yields.
https://ift.tt/3kUpOem
