A Preparation of Enantiomerically Enriched Axially Chiral β-Diketimines: Synthesis of (−)- and (+)-IAN Amine

Luesse, Sarah B.; Counceller, Carla M.; Wilt, Jeremy C.; Perkins, B. R.; Johnston, Jeffrey N.

doi:10.1021/ol800728b

Cited by 16 publications

(9 citation statements)

References 29 publications

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“…Another application of alkyl C–N coupling was described by Johnston and co-workers, who employed primary amine 53 as a chiral auxiliary to synthesize enantiomerically enriched β-diketimine ligand 56 ( Scheme 9 ). 80 The axially chiral species containing isoquinoline and 2-aminonaphthalene units is known as the IAN amine and it is an important building block for several asymmetric catalysts. ( S )-α-Methylbenzylamine ( 53 ) was combined with naphthol triflate to provide intermediate 54 in 52% yield.…”

Section: Alkylaminesmentioning

confidence: 99%

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

2016

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Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

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Section: Alkylaminesmentioning

confidence: 99%

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

2016

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“…Moreover, Johnston reported the synthesis of 1 within a patent filed in 2002, using ( S )‐(–)‐phenylethylamine 3 and ammonia chloride, in a Bucherer type reaction under harsh reaction conditions (Scheme , path a) . A different approach was published six years later by the same group making use of the palladium‐catalysed Buchwald‐Hartwig reaction to prepare 1 (Scheme , path b) . Furthermore, arylamine 2 can be prepared using this kind of transition‐metal catalysed reaction starting from 2,6‐dibromonaphthalene (Scheme ) .…”

Section: Methodsmentioning

confidence: 99%

“…This not only improves the yield but rather provides a more practical and easy to perform protocol. Besides the determined optical rotation for 1 which matches the literature, we validated that the chiral information is not affected during the C−N bond formation . Performing chiral HPLC yielded in an ee >99 % for 1 (for details check Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Optically Pure Arylamine Derivatives by Using the Bucherer Reaction

2017

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The Bucherer reaction is a common pathway for the conversion of 1‐ and 2‐naphthols into the corresponding 1‐ or 2‐naphthylamines, respectively. Mostly, only singular examples for its preparative use are reported since this particular transformation seems to be very sensitive to the reaction conditions. By choosing different phenolic substrates and chiral amines, we were able to prepare a broad scope of optically pure arylamines using this type of reaction. In contrast to alternative methods forming C−N aryl bonds such as Buchwald‐Hartwig or Chan‐Lam cross‐coupling reactions, no palladium or copper catalysts are required. The use of water as solvent and the easily available starting materials make this method to an attractive approach.

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“…As a remarkable example, the use isoquinoline-amino naphthalene (IAN) and related derivatives, which can be seen as N(sp 2 ),N(sp 3 ) analogues of QUINAP, have been scarcely investigated . A plausible explanation is the poor availability: There are no commercially available representatives, and their synthesis still requires chromatographic separation of diastereomeric mixtures (Scheme , eq 1), while the lack of a general and practical method of synthesis has also limited the structural diversity of known ligands of this type. Recently, we have reported a novel strategy for the synthesis of functionalized heterobiaryls based on dynamic kinetic asymmetric C–C and C–P bond formations starting from heterobiaryl triflates to ensure the formations of cationic oxidative addition intermediates (Scheme , eq 2).…”

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confidence: 99%

Synthesis of IAN-type N,N-Ligands via Dynamic Kinetic Asymmetric Buchwald–Hartwig Amination

et al. 2016

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The Pd 0 -catalyzed coupling of racemic heterobiaryl bromides, triflates or nonaflates with aryl/alkyl primary amines using QUINAP as the ligand provides the corresponding axially chiral heterobiaryl amines with excellent yields and enantioselectivities. Reactivity and structural studies of neutral and cationic oxidative addition intermediates support a dynamic kinetic asymmetric amination mechanism based on the labilization of the stereogenic axis in the latter, and suggest that coordination of the amine to the Pd center is the stereodetermining step.In recent years, significant advances have been achieved in the field of asymmetric cross-coupling, in particular for the synthesis of axially chiral biaryls.1 In sharp contrast, the direct asymmetric heteroaryl-aryl cross-coupling remains as an unmet challenge, 2 limiting the access to functionalized heterobiaryls with appealing structures for their use as ligands in asymmetric catalysis. As a remarkable example, the use Isoquinoline-Amino Naphthalene (IAN) and related derivatives, which can be seen as N(sp 2 ),N(sp 3 ) analogues of QUINAP, have been scarcely investigated.3 A plausible explanation is the poor availability: there are no commercially available representatives and their synthesis still requires chromatographic separation of diastereomeric mixtures (Scheme 1, eq. 1), 4 while the lack of a general and practical method of synthesis has also limited the structural diversity of known ligands of this type. Recently, we have reported a novel strategy for the synthesis of functionalized heterobiaryls based on dynamic kinetic asymmetric C-C 5 and C-P 6 bond formations starting from heterobiaryl triflates to ensure the formations of cationic oxidative addition intermediates (Scheme 1, eq. 2). Stimulated by the growing potential of related axially chiral heterobidentate ligands, 7 we decided to focus on the development of dynamic kinetic Buchwald-Hartwig (DYKAT: Dynamic Kinetic Asymmetric Transformation) amination of heterobiaryl electrophiles for the asymmetric synthesis of axially chiral IAN-type diamines (Scheme 1, eq. 3).The unprecedented asymmetric amination of heterobiaryls is a particularly challenging goal due to the specific conditions required. First, a strong base is generally needed to achieve good reactivities, so that compatibility issues might arise with the heteroScheme 1. Synthetic approaches to IAN amines biaryl triflates used in previous DYKAT processes. Second, the racemization barriers for IAN amines are significantly lower than those of arylated products I or QUINAP-type products II, 8 making necessary to work under exceptionally mild conditions. 9 In order to minimize the hydrolysis of the starting material, we started using the coupling between nonaflate (±)-1A 10 and aniline 5a as a model reaction for the synthesis of IAN 6Aa, using NaOtBu as the base, dry toluene as the solvent at 60 °C and 10 mol% Pd(dba)2/12 mol% ligand as the catalyst system (Scheme 2).Ligands that showed a good performance in related processes were select...

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A Preparation of Enantiomerically Enriched Axially Chiral β-Diketimines: Synthesis of (−)- and (+)-IAN Amine

Abstract: The preparation of an enantiomerically enriched beta-diketimine composed of isoquinoline and 2-aminonaphthalene (IAN amine) is described, thereby offering new opportunities in the synthesis of nonracemic beta-diketimine- and pyridine-based chiral catalysts.

Cited by 16 publications

References 29 publications

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Synthesis of Optically Pure Arylamine Derivatives by Using the Bucherer Reaction

Synthesis of IAN-type N,N-Ligands via Dynamic Kinetic Asymmetric Buchwald–Hartwig Amination

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