A Diastereoselective Intramolecular Hydroamination Approach to the Syntheses of (+)-, (±)-, and (−)-Pinidinol

Molander, Gary A.; Dowdy, Eric D.; Pack, Shawn K.

doi:10.1021/jo015603n

Cited by 83 publications

(21 citation statements)

References 22 publications

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“…Gold complexes still range among the most effective catalysts for the intramolecular amination of triple bonds (23), especially because unlike with the newer lanthanoide catalysts (where one often has to work in a glove-box!) (24,25), it is not necessary to thoroughly exclude humidity and oxygen, the gold-catalysts are quite robust. …”

Section: Reaction With Nitrogen-nucleophilesmentioning

confidence: 99%

Homogeneous gold catalysts and alkynes: A successful liaison

2003

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The use of the combination of homogeneous gold-catalysts and alkynes in organic synthesis is reviewed from its beginnings in C-N-bond formation to the newest developments in C-C-bond formation. The common basic principle of these reactions is discussed. Special attention is devoted to the question where the gold catalysts are superior to either other catalysts or more traditional synthetic approaches to the product molecules.Transition metal catalysis has become one of the most important tools in organic synthesis. It allowed entirely new transformations which were not possible previously by "traditional" organic reactions and thus significantly increased the efficiency of synthesis. It also made retrosynthetic analysis more demanding as many of the transformations go along with a remarkable increase in molecular complexity (1) which makes the relationship between the product and the starting material more difficult to recognize. In many of these reactions, especially in the case of late transition metals, C-C multiple bonds in either alkenes or alkynes, are the site of reaction. Theoretical backgroundIn the field of homogeneous gold catalysis the alkynes 1, which have the structural motive of a C-C-triple bond, belong to the most popular substrates. The reason for that popularity is the high reactivity of the alkynes which originates from their electronic structure (2). Often the corresponding alkenes with their C-C-double bond are less reactive.On one hand, the alkynes possess two orthogonal -orbitals high in energy occupied by two electrons each. These react with electrophilic reagents (E) like halogens in organic synthesis or electrophilic metal centers like gold (in the oxidation states I or III) in the field of transition metal catalysis (3,4). In the interaction with a metal center both the -orbital in the plane of metal co-ordination and theorbital perpendicular to it are able to interact with the dorbitals of the metal.On the other hand, the lowest unoccupied orbital of the alkynes is low in energy and thus eagerly react with strong nucleophiles like for example ethyne 2 with catalytical amounts of alkoholates in the Reppe synthesis of vinyl ethers 3 (5).Most unfortunately, weak nucleophiles (Nu) do not react directly with the alkynes, although this is often desired in organic synthesis. But the alkyne can be activated by co-ordination to the electrophilic gold complexes as mentioned above. This co-ordination withdraws electron

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Section: Reaction With Nitrogen-nucleophilesmentioning

confidence: 99%

Homogeneous gold catalysts and alkynes: A successful liaison

2003

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“…[6] On the otherh and, hydroamination of d,eunsaturated amines affords 2,6-cis-piperidines regardless of the substitution patterns on the nitrogen. [7,8] We recently disclosed an unprecedented hydroamination of g,d-alkenyl oximes mediated by potassium bases, such as K 3 PO 4 and tBuOK. The reaction yieldedf ive-membered cyclic nitrones, which were formed through an ucleophilic amination of unactivated alkenes by the oxime sp 2 -hybridized nitrogen (Scheme 1b).…”

Section: Introductionmentioning

confidence: 99%

Diastereo‐Divergent Synthesis of Saturated Azaheterocycles Enabled by tBuOK‐Mediated Hydroamination of Alkenyl Hydrazones

Kaga

Peng

Hirao

et al. 2015

Chemistry A European J

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Diastereo-divergent synthesis of saturated azaheterocycles has been achieved by tBuOK-mediated hydroamination of alkenyl hydrazones. DFT calculations suggested that the cation-π interactions between a potassium cation and aryl substituents on hydrazones give rise to 2,5-cis selectivity in pyrrolidines, which were synthesized by the reaction of γ,δ-unsaturated N-benzyl hydrazones. By contrast, 2,5-trans selectivity was observed when an isopropyl group was used as the substituent on hydrazones. An unusual 2,6-trans selectivity in piperidine formation was also realized using the present strategy.

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“…2). 8 Substrates 1 and 5 show higher diastereoselectivity (.4:1) than their non-aromatic counterpart (,1:1). 1 The aromatic ring might act to stiffen the transition state of the second C -C cyclization, resulting in greater selectivity.…”

Section: ð6þmentioning

confidence: 93%