Moreover, mukaiyamamannich addition of the nitrone 1k derived from cinnamaldehyde and pfluoronitrobenzene produced the adduct 3k in 85% yield without any decomposition or polymerisation under the present reaction conditions table 2, entry 11. Catalytic enantioselective vars leading references. Expedient mukaiyama type mannich reaction catalyzed by lithium chloride article pdf available in synlett 1010. Pdf expedient mukaiyamatype mannich reaction catalyzed. View the article pdf and any associated supplements and figures for a period of 48 hours.
A reliable, catalytic asymmetric vinylogous mukaiyama mannich reaction of pyrrolebased silyl dienolates is introduced that is particularly apt for alkyl and. A highly efficient mukaiyamamannich reaction of nboc. This chiral disulfonimide catalyst displays high catalytic efficacy toward the asymmetric mukaiyama mannich reaction of imines with ketene silyl acetals leading to. The first enantioselective organocatalytic mukaiyama.
May 23, 2012 among them, the mukaiyamamannich reaction performed with silyl enol ethers and sulfonyl aldimines, catalyzed by a chiral lewis acid complex, is one of the most important synthetic methods. C enantioselective catalytic mukaiyama oxocarbenium aldol. Zhou and coworkers recently developed an asymmetric mukaiyama mannich reaction between fluorinated silyl enol ethers and ketimines catalyzed by a hydroquinine derived bifunctional urea catalyst 2 scheme 3 25. Pot enol silane formationmukaiyamamannich addition of. New modified protocols allow syn or anti selective transformations and even the selective preparation of enantiomers. For computational studies of the mechanism of this reaction type, see. Diastereo and enantioselective catalytic vinylogous. A catalytic enantioselective mukaiyamamannich reaction of cyclic cacylimines with difluoroenoxysilanes is reported. Other bases including lda, lihmds, tbuli, khmds and nbumgcl were also screened, only the tbuli offered comparable results entries 26. A new binolderived chiral disulfonimide has been developed by introducing 4methyl3,5dinitrophenyl substituents at its 3 and 3.
This represents the first auicatalyzed mukaiyamamannich reaction, and the corresponding nonfluorinated enol silyl ether proves to be even much more reactive under the same conditions. The vinylogous aldol reaction synthesis and methodology evans group seminar february 15, 2002 jason burch i. Enantioselective anti mannich reactions are, however, considerably rarer. Reduction with redal to give 1,3diols kishi tetrahedron lett. Catalytic asymmetric mukaiyamamannich reaction of cyclic c. The mechanism begins by coordination of the aldehydes oxygen to titanium, which activate the carbonyl for attack while also releasing a chloride ion. Efficient entry to the pyrroloquinoline core of martinella. A catalytic enantioselective mukaiyama mannich reaction of cyclic cacylimines with difluoroenoxysilanes is reported. Mannichtype reactions are widely recognized as a powerful method for constructing a variety of baminoketones 1 6. Two key features render the mannichreaction and its products very attractive. Apparently, direct use of inactivated ketones as a donor would be of great practical value. Catalytic asymmetric mukaiyamamannich reaction of cyclic.
B substrate scope foracidcatalyzed mannich reaction. The longstanding problem of the chiral phosphoric acidcatalyzed asymmetric mukaiyama mannich reaction that requires a 2hydroxyphenyl moiety was solved by this disulfonimide catalyst. Recent advances in bismuth mediated aldol and mannich. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary. The use of nitrones as coupling partners in 1,3dipolar cycloaddition reactions has been well documented. The mannich reaction is an example of nucleophilic addition of an amine to a carbonyl group followed by dehydration to the schiff base. Apparently, the nitrones derived from aromatic aldehydes or nitroarene bearing electrondonating. Reaction was performed with the trimethylsilyl ketene acetal derived from methyl cyclohexanecarboxylate.
Mechanism of aldol and mannich reactions in aldol reactions, proline effects reaction through enamine catalysis, as shown in scheme 2. Chapter 2 total syntheses of the spiculisporic acids. A catalystfree, environmentally benign threecomponent vinylogous mukaiyamamannich reaction of pyrrolebased silyl dienolates is presented, which works effectively in both aqueous and solventfree environments. To our delight, the model reaction of the lithium enolate of 1b and benzaldehyde in thf gave a1 with good yield and synselectivity table 2, entry 1. The synthetic utility of this protocol is highlighted by efficient conversion of the.
Herein, the first organocatalytic enantioselective mukaiyamamannich reaction employing isatin. Lithium acetatecatalyzed mannich type reaction between trimethylsilyl enolates and aldimines in a watercontaining dmf chemistry letters. Nucleofili eterociclici azotati in reazioni di mannich. Lithium acetatecatalyzed mannichtype reaction between trimethylsilyl enolates and aldimines in a watercontaining dmf chemistry letters. Among them, the mukaiyamamannich reaction performed with silyl enol ethers and sulfonyl aldimines, catalyzed by a chiral lewis acid complex, is one of the most important synthetic methods. Strip enables the enantioselective synthesis of a series of novel difluoroalkylated indolin3ones bearing a quaternary stereocenter in up to 97% yield and 98% ee. The reaction is general to a range of silyl trifluoromethanesulfonates and n. Michaelmannichhemiaminalizationdehydration cascade. The supporting information is available free of charge on the acs publications website at doi. Pot enol silane formationmukaiyamamannich addition of ketones, amides, and thioesters to nitrones in the presence of trialkylsilyl trifluoromethanesulfonates, european journal of organic chemistry on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Organocatalytic mukaiyama mannich reactions of 2,5bis. Abstract mukaiyamamannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of. Onepot mukaiyamamannich reaction of aldehydes, amines and.
Type mannich reaction catalyzed by lithium chloride. Apparently, direct use of inactivated ketones as a. Iodide counterion, weakly coordinating peripheral ethereal ligands et2o of mgii, and a noncoordinating reaction media i. Proposed mechanism of the catalytic mukaiyama anhydride mannich reaction. Organocatalytic enantioselective mukaiyamamannich reaction. An efficient, mild, solventfree, onepot threecomponent mannich reaction catalyzed by c 4 h 12 n 2 2 bicl 6clh 2 o h. Both aldol reaction and aldol condensation are overall reversible. B substrate scope for acidcatalyzed mannich reaction. However, if the ketonederived silyl enol ether reacts with the nitrone via a mukaiyamamannichtype addition. The mannich reaction is an organic reaction which consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group by formaldehyde and a primary or secondary amine or ammonia. Onepot mukaiyamamannich reaction of aldehydes, amines and silyl enol diazoacetate catalyzed by mgi2 etherate. This variation on the traditional mukaiyamamannich reaction, utilizing nitrones as the electrophilic reagent, is rare due to the competing cyclization reaction. Request pdf a powerful chiral phosphoric acid catalyst for enantioselective mukaiyamamannich reactions a new binolderived chiral phosphoric.
Direct asymmetric antimannichtype reactions catalyzed by a. Asymmetric organocatalytic decarboxylative mannich reaction. An efficient enantiocontrolled entry to martinella alkaloids was achieved based on the unexpected discovery that a catalytic amount of khdicyclohexyl18crown6 induced an intramolecular mukaiyamamannich reaction of imine 3, leading to a cascade sequence involving a novel silyl group migration to furnish the pyrroloquinoline core 6. Catalytic methods for the addition of ketonederived silyl enol ethers to other imine equivalents have been reported. Request pdf a powerful chiral phosphoric acid catalyst for enantioselective mukaiyamamannich reactions a new binolderived chiral phosphoric acid bearing 2,4,6trimethyl3,5dinitrophenyl. Pdf the mannich reaction of methylsilyl enol ether with arylaldimine proceeded in the presence of a catalytic amount of lith ium chloride in. Under the catalysis of hydroquinine derived bifunctional urea, cyclic nsulfonyl ketimines readily react with fluorinated enol silyl ethers to afford benzosultam based c. Pdf expedient mukaiyamatype mannich reaction catalyzed by. The mukaiyama aldol addition is an organic reaction used to convert an aldehyde and a silyl enol ether to a 1,3 ketol using a lewis acid catalyst such as ticl 4, followed by aqueous workup. Supersilyl group as novel carboxylic acid protecting.
A similar trend was reported by kobayashi in a competition reaction in which bicl3 proved to be aldimine selective. In the acid catalyzed mechanism both carbonyl compounds get protonated at the oxygen. Organocatalytic enantioselective mukaiyamamannich reaction of. An efficient mukaiyamamannich reaction of difluoroenoxysilanes with unactivated ketimines enabled by 5 mol% of scotf3 is reported here. Herein, the first organocatalytic enantioselective mukaiyama mannich reaction employing isatin. The open transition state is preferred, but the outcome of the reaction synanti depends on the size of substituents and on the lewis acid. The involvement of the mannich reaction has been proposed in many biosynthetic pathways, especially for alkaloids.
New modified protocols allow syn or antiselective transformations and even the selective preparation of enantiomers. Nov 21, 2017 a catalytic enantioselective mukaiyamamannich reaction of cyclic cacylimines with difluoroenoxysilanes is reported. In addition, complete chemoselectivity was observed between mukaiyama aldol and mannich type reaction. Enantioselective antimannich reactions are, however, considerably rarer. Niiicatalyzed enantioselective mukaiyamamannich reaction between supplementary files. Pot enol silane formationmukaiyamamannich addition. Direct asymmetric antimannichtype reactions catalyzed by. Iminium ion 6, created by attack of the enamine on the re. Expedient mukaiyamatype mannich reaction catalyzed by lithium chloride article pdf available in synlett 1010.
However, mannichtype reaction of imines with 2silyloxydienes, which provides easy access to. This chiral disulfonimide catalyst displays high catalytic efficacy toward the asymmetric mukaiyamamannich reaction of imines with ketene silyl acetals leading to. The reaction course is effectively orchestrated by the hoveydasnapper amino acidbased chiral ligandsilveri catalyst combination to produce valuable vicinal diamino carbonyl compounds in high. The use of iminium catalysis has provided a new strategy for the enantioselective addition of 2silyloxy furans to unsaturated aldehydes to generate a variety of butenolide systems, an important chiral synthon found among many natural isolates. Niiicatalyzed enantioselective mukaiyamamannich reaction. Enamine 5 is formed from the pyrrolidine nitrogen and the carbonyl donor. Asymmetric organocatalytic decarboxylative mannich reaction using.
Since its discovery by mukaiyama in 1974,8 the mukaiyama michael reaction of silyl enol ethers with a,bunsaturated carbonyl compounds has become a powerful technique for the stereoselective formation of carboncarbon bonds under mild reaction conditions. The synthetic utility of this protocol is highlighted by efficient conversion of the products to the. Ph 3 pauotf is identified as a powerful catalyst for the addition of difluoroenol silyl ethers to nboc isatin ketimines and other two kinds of active cyclic ketimines. A highly efficient mukaiyamamannich reaction of nboc isatin. The direct organocatalytic asymmetric mannich reaction. Chemoselective aldol reaction of silyl enolates catalyzed. Reaction was performed with the trimethylsilyl ketene acetal. Mannichtype reaction of aldimines with 2silyloxydienes. Pot enol silane formationmukaiyamamannich addition of ketones, amides, and thioesters to nitrones in the presence of trialkylsilyl trifluoromethanesulfonates downey 20 european journal of organic chemistry wiley online library. Calcium catalyzed mukaiyamamannich addition of silyl enol. Since its discovery by mukaiyama in 1974,8 the mukaiyamamichael reaction of silyl enol ethers with a,bunsaturated carbonyl compounds has become a powerful technique for the stereoselective formation. The reaction was developed by teruaki mukaiyama at mitsui petrochemical.
Intersecting the growing principles of asymmetric and organocatalysis, different protocols were developed. Supersilyl group as novel carboxylic acid protecting group. Mechanism of the mukaiyama aldol addition the open transition state is preferred, but the outcome of the reaction synanti depends on the size of substituents and on the lewis acid. Mannichtype reactions of aldimines and hetero dielsalder. Recent advances in bismuth mediated aldol and mannich reactions. Transition metal saltcatalyzed direct threecomponent mannich reactions of aldehydes, ketones, and carbamates. Switching the solvent to toluene or ether proved to be detrimental to the.
Selfpromoted aldol reaction between aldehyde having lewis base moiety and trimethylsilyl enolate chemistry letters. Mannichtype reactions of aldimines with silyl enolates and hetero dielsalder reactions of aldehydes with danishefskys diene in the presence of anion catalysts derived from proline were performed to afford the corresponding products in high yields. The first catalytic asymmetric mukaiyamamannich reaction of fluorinated silyl enol ethers and ketimines is developed. The schiff base is an electrophile which reacts in the second step in an electrophilic addition with a compound containing an acidic proton which is, or had become an enol. A disulfonimide catalyst for highly enantioselective. Organocatalytic enantioselective mukaiyama mannich reaction of fluorinated enol silyl ethers and cyclic nsulfonyl ketimines jinsheng yu a and jian zhou,a,b a shanghai key laboratory of green chemistry and chemical process, school of chemistry and molecular engineering, east china normal university, shanghai 200062, p. Mukaiyama type aldol coupling of typical silyl enolates 2. Consequently, if an aldol, the product of aldol reaction, or an. Pot enol silane formationmukaiyamamannich addition of ketones, amides, and thioesters to nitrones in the presence of trialkylsilyl trifluoromethanesulfonates.
Onepot enol silane formationmukaiyamamannich addition of. The mannich reaction is an organic reaction used to convert a primary or secondary amine and two carbonyl compound one nonenolizable and one enolizable to a. Aqueous and solventfree uncatalyzed threecomponent. The mukaiyama hydration is an organic reaction involving formal addition of an equivalent of water across an olefin by the action of catalytic bis acetylacetonatocobalt ii complex, phenylsilane and atmospheric oxygen to produce an alcohol with markovnikov selectivity. A catalyst screen forenantioselective mukaiyamamannich reaction. A catalyst screen for enantioselective mukaiyamamannich reaction.
This includes the reaction of nitrones with ketonederived silyl enol ethers, which has been shown to lead to the formation of isoxazolidines fig. Asymmetric organocatalytic decarboxylative mannich. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective ee up to 99 % and diastereoselective synanti up to 99. The open transition state is preferred, but the outcome of the reaction synanti depends on the size of substituents. Nov 11, 20 2 rate enhancement by water in the mukaiyama aldol reaction. An efficient, mild, solventfree, onepot threecomponent mannich reaction catalyzed by c 4 h 12 n 2 2 bicl 6 clh 2 o.
1200 259 562 537 1564 209 395 138 434 473 1544 1546 331 1083 1575 1452 996 652 1538 1282 325 1423 1163 1550 141 265 1125 400 285 471 139 1217 1213 1224 913 949 1136 1085 585 731 376 759 1058 358 1126 1135 819 596 185 1153