A Catalytic Asymmetric 6 π Electrocyclization: Enantioselective Synthesis of 2‐Pyrazolines

Müller, Steffen; List, Benjamin

doi:10.1002/anie.200905035

Cited by 129 publications

(59 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although pharma researchers now routinely and reliably separate enantiomers by preparative chiral HPLC (24,25), an asymmetric variant of the present reaction sequence could be contemplated through the use of chiral directing groups or asymmetric electrocylization catalysts (26,27). Moreover, the addition of many other types of nucleophiles should be possible, and the 1,2-dihydropyridine intermediates 4 could conceivably react with electrophiles other than proton to enable the regio- and stereoselective synthesis of even more densely substituted products.…”

mentioning

confidence: 99%

Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis

Duttwyler

Chen

Takase

et al. 2013

Science

View full text Add to dashboard Cite

Piperidines are prevalent in natural products and pharmaceutical agents and are important synthetic targets for drug discovery and development. We report a methodology that provides highly substituted piperidine derivatives with regiochemistry selectively tunable by varying the strength of acid used in the reaction. Readily available starting materials are first converted to dihydropyridines via a cascade reaction initiated by rhodium-catalyzed C–H bond activation. Subsequent divergent regio- and diastereoselective protonation of the dihydropyridines under either kinetic or thermodynamic control provides two distinct iminium ion intermediates that then undergo highly diastereoselective nucleophilic additions. X-ray structural characterization of both the kinetically and thermodynamically favored iminium ions along with density functional theory calculations provide a theoretical underpinning for the high selectivities achieved for the reaction sequences.

show abstract

mentioning

confidence: 99%

Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis

Duttwyler

Chen

Takase

et al. 2013

Science

View full text Add to dashboard Cite

show abstract

“…Some of these compounds also exhibit antioxidant, anti-inflammatory and analgesic properties [7][8][9]. The crystal structure of the title compound has recently been determined, but at room temperature only and without any structural discussion [10]. In view of the pharmacological importance of the title compound this is a non-acceptable starting point for conducting a more profound study of structure-activity relationships.…”

Section: Discussionmentioning

confidence: 99%

Redetermination of the structure of 3-methyl-1,5-diphenyl-4,5-dihydro- 1H-pyrazole, C16H16N2

Samshuddin

Narayana

Yathirajan

et al. 2013

Zeitschrift Für Kristallographie - New Crystal Structures

View full text Add to dashboard Cite

“…These compounds were prepared in situ from a,b-unsaturated enones 244 and phenylhydrazine 245, to give 2-pyrazolines 247 in high yields and enantioselectivities, Scheme 3.79 [100].…”

Section: Electrocyclizationmentioning

confidence: 99%

Organocatalyzed Cycloadditions

Hong¹

2011

Enantioselective Organocatalyzed Reactions II

View full text Add to dashboard Cite

Cycloadditions have been for a long time one of the most useful reactions in organic synthesis. Recently, the ability to promote the reactions by organocatalysts further expands the realm of its synthetic application. This review aims to highlight the recent advances in this area with particular emphasis on the asymmetric cycloaddition promoted by organocatalysts. IntroductionGenerating selectively the maximum number of bonds and stereogenic centers in a one-step (or one-pot) reaction constitute to be of key interest in synthetic chemistry. Among many methodologies for the objective, cycloaddition stand out. While searching for a better and tunable catalyst able to promote a wide spectrum of cycloaddition, organocatalysis was revealed as a powerful tool for efficient operations and many other merits, e.g., high stereoselectivity, moisture and air resistant, environmental benign and user friendly. Surprisingly, organocatalytic synthesis was virtually dominant for few decades until just the turn of this century [1]; nevertheless, it soon become the focal point, and it has occupied an important chapter in the modern synthetic chemistry [2]. In a very short period of time, more than hundred review articles of organocatalytic reactions were reported, and the papers are continuing to appear for summarizing up the thriving and robust subject. Several theoretical studies, including the computational Intramolecular CycloadditionsIn 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,b-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malimide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan's conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation), Scheme 3.2 [7]. In 2003, an interesting intramolecular organocatalytic [3 + 2] dipolar cycloaddition of an enynoate (19) catalyzed by PBu 3 was developed by Krische and his coworker in the total synthesis of (±)-hirsutene (21), Scheme 3.6 [12]. The intramolecular phosphane-catalyzed [3 + 2] dipolar cycloaddition provides a concise approach to the linear triquinane hirsutene, whereby three contiguous stereogenic centers are created and controlled in a single reaction step.A light-driven enantioselective organocatalysis intramolecular [2 + 2] photocycloaddition of quinolone (24) [4 + 2] cycloadditions. The enantioselectivity was rationalized by the fact that selective formation of the (E)-iminium isomer to avoid nonbonding interactions between the substrate olefin and the geminal methyl substituents and the benzyl group on the catalyst framework which effectively shields the re face of the dienophile, leaving the si face exposed to cycloadditio...

show abstract

A Catalytic Asymmetric 6 π Electrocyclization: Enantioselective Synthesis of 2‐Pyrazolines

Cited by 129 publications

References 69 publications

Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis

Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis

Redetermination of the structure of 3-methyl-1,5-diphenyl-4,5-dihydro- 1H-pyrazole, C16H16N2

Organocatalyzed Cycloadditions

Contact Info

Product

Resources

About