Nucleophilic Addition to 3-Substituted Pyridinium Salts:  Expedient Syntheses of (−)-L-733,061 and (−)-CP-99,994

Lemire, Alexandre; Grenon, M.; Pourashraf, Mehrnaz; Charette, André B.

doi:10.1021/ol048624n

Cited by 90 publications

(31 citation statements)

References 22 publications

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“…Furthermore, stereoselective variants have been reported. Comins, 9 Wanner, 10 and Charette 11 have pioneered the use of chiral auxiliaries to control the facial selectivity of Grignard additions to pyridinium salts, though a blocking group at the C3 position is often required for high regio- and diastereoselectivity.…”

Section: Introductionmentioning

confidence: 99%

Nickel-catalyzed enantioselective arylation of pyridine

2016

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We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed in situ from pyridine and a chloroformate. This reaction provides enantioenriched 2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step.

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Section: Introductionmentioning

confidence: 99%

Nickel-catalyzed enantioselective arylation of pyridine

2016

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“…In our opinion the following examples represent the most efficient synthesis of 3-piperidinols of type B in terms of step-economy (<10 steps to establish the core motif B ): 1. Charette [36] prepared the less bioactive enantiomers of L-733,060 and CP-99,994 through nucleophilic additions to chiral pyridylium salts and subsequent hydrogenation. 2.…”

Section: Introductionmentioning

confidence: 99%

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

Huy

Westphal

Koskinen

2014

Beilstein J. Org. Chem.

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SummaryA concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.

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“…[73] Both the strong directing effect of the imidate nitrogen atom and stereoelectronic effects led to the formation of 2,3-disubstituted dihydropyridines in good yields and regioselectivities (Table 16). [73] Both the strong directing effect of the imidate nitrogen atom and stereoelectronic effects led to the formation of 2,3-disubstituted dihydropyridines in good yields and regioselectivities (Table 16).…”

Section: Pauson-khand Reactionsmentioning

confidence: 99%

Removable Directing Groups in Organic Synthesis and Catalysis

2011

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Directing groups have been widely used in recent years to achieve control over all aspects of reaction selectivity in a wide range of transformations involving transition-metal catalysis and organometallic reagents. In cases when the existing functional group within a substrate is unsuited to achieve efficient intramolecular delivery of a reagent or catalyst, the specific introduction of an appropriately designed removable reagent-directing group can be a solution to this problem. In this Review we give an overview of the state of the art in this area, including the stoichiometric and catalytic use of directing groups.

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Nucleophilic Addition to 3-Substituted Pyridinium Salts: Expedient Syntheses of (−)-L-733,061 and (−)-CP-99,994

Cited by 90 publications

References 22 publications

Nickel-catalyzed enantioselective arylation of pyridine

Nickel-catalyzed enantioselective arylation of pyridine

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

Removable Directing Groups in Organic Synthesis and Catalysis

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