Enantiospecific Synthesis of Allylamines via the Regioselective Rhodium-Catalyzed Allylic Amination Reaction

Evans, P. Andrew; Robinson, A.; Nelson, Jade D.

doi:10.1021/ja991089f

Cited by 136 publications

(46 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar mode of reactions is very unlikely here because hard nucleophiles such as arylboronic acids react with the same catalyst and substrate to give retention of stereochemistry (58). A net S N 2Ј displacement of the bridgehead leaving group is observed that is also different from what is obtained with rhodium catalysts and allylic carbonates where nucleophilic attack occurs at the same carbon from which the leaving group departs (11)(12)(13)(14)(15)(16)(17). Nucleophilic attack at the carbon bearing the leaving group has also been documented with Ru (48) and Fe (44) catalysts.…”

Section: Discussionmentioning

confidence: 73%

“…The formation of the 1,2-trans products is atypical for ring opening reactions of oxabicyclic alkenes, which usually generate the syn-1,2 diastereomers via exo nucleophilic attack (1,2). Furthermore, regio-and stereochemical results diverge from previously documented rhodium-catalyzed reactions with allylic carbonates (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The observations obtained with oxabicyclic alkenes find little precedent when compared to other allylic functionalizations including those catalyzed by Pd (refs.…”

mentioning

confidence: 89%

See 1 more Smart Citation

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Lautens

Fagnou²

2004

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

Catalyst and substrate studies have been performed on the rhodium-catalyzed asymmetric ring opening reaction. A working model is advanced that involves oxidative insertion with retention to form an organorhodium intermediate that then undergoes nucleophilic attack with inversion. Kinetic and competition experiments have uncovered evidence for a proton transfer step in the catalytic cycle that may activate both the allylrhodium intermediate and the nucleophile. We have also conducted experiments designed to understand which properties of the PPF-P t Bu2 ligand contribute to the high reactivities and enantioselectivities.W e have previously reported that chiral rhodium(I) catalysts induce ring opening oxa-and azabicyclic alkenes with a variety of soft nucleophiles such as alcohols, phenols, amines, anilines, malonates, and carboxylates in high yield and enantioselectivity (1-8). The products are generated by an S N 2Ј nucleophilic displacement of the bridgehead leaving group with inversion providing the 1,2-trans product as one regio-and diastereomer. The formation of the 1,2-trans products is atypical for ring opening reactions of oxabicyclic alkenes, which usually generate the syn-1,2 diastereomers via exo nucleophilic attack (1, 2). Furthermore, regio-and stereochemical results diverge from previously documented rhodium-catalyzed reactions with allylic carbonates (9-18). The observations obtained with oxabicyclic alkenes find little precedent when compared to other allylic functionalizations including those catalyzed by Pd (refs. 19 In this report we describe catalyst and substrate studies and advance a mechanistic working model that rationalizes the stereochemical outcome and other experimental observations (Scheme 1). We have also conducted experiments designed to understand the properties of the PPF-P t Bu 2 ligand that contribute to high reactivities and enantioselectivities.Experimental procedures and characterization data can be found in Supporting Text, which is published as supporting information on the PNAS web site. Ligand Studies: Variations on the Josiphos Template and Other Ligand MotifsSeveral structural elements are present on the PPF scaffold that could contribute to its successful application in these reactions (51-53). PPF has elements of central and planar chirality as well as two phosphine atoms that differ both sterically and electronically. Two methods were used to determine the influence of the ligand on the rate. In cases where a significant difference in rate was observed, percent conversion vs. time, as determined by crude 1 H NMR, was used to quantify the reactivity of the catalyst. In cases where a more precise measurement of rate was desired, kinetic runs were performed.By comparing the reactivity and enantioselectivity of ligands 3 and 4, two trends emerge (Scheme 2). First, by increasing the steric bulk ( t Bu Ͼ Cy) the enantioselectivity is increased from 88% with 3 to 96% enantiomeric excess (ee) with the bulkier t Bu 2 P ligand 4. This increase in enantioselectivity comes at ...

show abstract

Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 89%

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Lautens

Fagnou²

2004

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23][24] The regioselectivities in reactions using rhodium, [25][26][27][28][29][30][31][32][33] iridium, [34][35][36][37][38] and ruthenium [39][40][41] complexes are quite different from those of palladium-catalyzed reaction. Therefore, chiral iridium complexes controlling regio-and enantioselectivities have been a subject of current interest.…”

Section: Resultsmentioning

confidence: 99%

Regio- and Enantioselective Allylic Substitution with Less Active N- or O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine

Miyabe

Moriyama

Takemoto

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Enantioselective transition metal-catalyzed allylic substitutions have been developed as fundamentally important crosscoupling reactions. [1][2][3][4][5][6][7][8] In general, the heteroatom nucleophiles in these reactions have been largely limited to alkylamines, anilines, carboxylates and phenols. Our laboratory is interested in searching the synthetically useful heteroatom nucleophiles for the synthesis of functionalized allylic compounds (Fig. 1).9) As our successful examples, we have recently reported the utility of oximes 1 and guanidines 5 and 6 as nucleophiles in the transition metal-catalyzed allylic substitution. [10][11][12][13][14] Hydroxylamines are also attractive synthetic reagents for allylic substitution, since they have nitrogen and oxygen atoms as nucleophiles. However, the allylic substitution with hydroxylamines has not been studied well and is limited to a simple palladium-catalyzed amination 15,16) ; thus, there are no reports on asymmetric reactions. We have recently reported that hydroxylamines 2 and 3 having an N-electron-withdrawing substituent, also known as hydroxamic acids, act as reactive oxygen nucleophiles in the enantioselective allylic substitution ( Fig. 1). 17,18) As a part of our program directed toward searching the synthetically useful heteroatom nucleophiles, we describe in detail the study of hydroxylamines 4 as nitrogen nucleophiles in the regio-and enantioselective iridium-catalyzed allylic substitutions. 19) In this study, we also expected that comparison with alkylamines, p-anisidine, and 4-methoxyphenol would lead to informative suggestions regarding the asymmetric reaction using the iridium complex of pybox (bis(oxazolinyl)pyridine) ligand. Results and DiscussionControlling both regio-and enantioselectivities has been of great importance in the allylic substitution of unsymmetrical substrates with heteroatom nucleophiles. [20][21][22][23][24] The regioselectivities in reactions using rhodium, [25][26][27][28][29][30][31][32][33] iridium, [34][35][36][37][38] and ruthenium [39][40][41] complexes are quite different from those of palladium-catalyzed reaction. Therefore, chiral iridium complexes controlling regio-and enantioselectivities have been a subject of current interest. Recently, we reported that the iridium-complex of pybox catalyzed allylic substitution of unsymmetrical substrates to form branched products with good enantioselectivities. 13,14,17,19) Prior to exploring the enantioselective reaction, we first investigated the viability of hydroxylamine 4A having N-benzoyl and O-benzyl groups (Chart 1). Although the reaction of 4A with carbonate 7 was less effective in the absence of a base, the reaction of 4A with acetate 8 proceeded smoothly by employing Et 2 Zn as a base to give the branched product 9Aa in 60% yield without formation of the linear product.Based on these results, we next investigated iridium-catalyzed asymmetric allylic substitution with hydroxylamine 4A under basic conditions (Chart 2). In this study, phosphate 10a was employed as an unsymm...

show abstract

“…Although exceptions have been found (18), most palladium catalysts generate a terminal achiral allylic amine product from a linear allylic electrophile or a racemic branched allylic electrophile. Thus, a catalyst that would convert either a racemic branched allylic electrophile or an achiral terminal electrophile enantioselectively to a branched chiral amine product would provide a valuable synthetic tool (19)(20)(21). We recently reported an iridium complex containing a phosphoramidite ligand that catalyzes the reaction of amines with achiral linear allylic carbonates to form the branched allylic amine products with high enantioselectivity and regioselectivity (Eq.…”

mentioning

confidence: 99%

“…For example, the reaction of allyl amine occurs with an equally high 92% enantiomeric excess. The product of this reaction is suitable for ring-closing metathesis (27)(28)(29) to form optically active 3-pyrrolines (19) or, after reduction of the CAC bond, pyrrolidines.…”

mentioning

confidence: 99%

Editing the stereochemical elements in an iridium catalyst for enantioselective allylic amination

Leitner

Shu

Hartwig

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Individual diastereomeric phosphoramidites and mixtures of diastereomeric phosphoramidites were evaluated in the iridiumcatalyzed amination of allylic carbonates. The original process was conducted with a phosphoramidite ligand containing a resolved 2,2-dihydroxy-1,1-binaphthyl (BINOL) group and a diastereomerically and enantiomerically pure bis(phenethyl)amino group. Evaluation of the structure of the active catalyst and relative rates for reactions in the presence of catalysts containing diastereomeric ligands led to the identification of a phosphoramidite that provided the amination product with enantiomeric excess similar to the original, more structurally and stereochemically complex ligand and that contains a racemic BINOLate and an N-benzylphenethylamino group on phosphorus.B iologically active molecules with stereocenters alpha to nitrogen range from single enantiomer pharmaceuticals to alkaloid natural products (1, 2). The classic routes to such chiral amines include resolution with chiral acids or initiation of the synthesis with a member of the existing optically active chiral pool that includes naturally occurring amino acids. However, the resolution typically requires disposal of at least half of the chiral amine, and many targets require a multistep synthesis from materials in the chiral pool. Thus, many synthetic approaches have been investigated for the preparation of ␣-chiral amines in an enantioselective manner.Two common approaches involve hydrogenation of an imine (3-5) and additions of nucleophiles to imines (6-12). The hydrogenation of imines is not yet a general process and can be used to form only primary or secondary amines. The addition of carbon nucleophiles to imines with high enantioselectivity has been limited also, and the highest selectivities typically require a chiral substituent at nitrogen that would ultimately be disposed or would require recycling (8). An alternative approach involves enantioselective formation of the carbon-nitrogen bond in the amine (6,7,13,14).Transition metal-catalyzed reactions of nitrogen nucleophiles with allylic electrophiles (15) provide the opportunity to form the carbon-nitrogen bond in an amine with stereoselectivity that is based on a catalytic amount of a chiral ligand bound to the transition metal. In most cases, a palladium catalyst has been used for this transformation (16,17). Although exceptions have been found (18), most palladium catalysts generate a terminal achiral allylic amine product from a linear allylic electrophile or a racemic branched allylic electrophile. Thus, a catalyst that would convert either a racemic branched allylic electrophile or an achiral terminal electrophile enantioselectively to a branched chiral amine product would provide a valuable synthetic tool (19-21). We recently reported an iridium complex containing a phosphoramidite ligand that catalyzes the reaction of amines with achiral linear allylic carbonates to form the branched allylic amine products with high enantioselectivity and regioselectivity (Eq. 1 and ...

show abstract

Enantiospecific Synthesis of Allylamines via the Regioselective Rhodium-Catalyzed Allylic Amination Reaction

Cited by 136 publications

References 12 publications

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Regio- and Enantioselective Allylic Substitution with Less Active N- or O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine

Editing the stereochemical elements in an iridium catalyst for enantioselective allylic amination

Contact Info

Product

Resources

About