Methods for Total Synthesis of Steroids. XVIII.1 Δ14 -16-Keto Steroid Approach to Ring D. H.2 Introduction of 17-Carboxy Group. Synthesis of 14α,17β and 14β,17α Isomers of rac-Estra-5(10),6,8-triene-17-carboxylic Acid

Wilds, A. L.; Harnik, M.; Shimizu, Ruth Zeitschel; Tyner, David A.

doi:10.1021/ja00956a036

Cited by 7 publications

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“…Following hydrogenation and Krapcho decarboxylation, the monoester 17 was obtained, demonstrating removal of an activating group in the Michael donor. Furthermore, the monoester 17 resembles a previously described steroidal intermediate 42 ( cf. Fig.…”

Section: Resultsmentioning

confidence: 64%

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Liu¹,

Shirley²,

Van³

et al. 2013

Nature Chem

128

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Toward improving synthetic efficiency, organic chemists have turned to bioinspired organocascade or domino processes that generate multiple bonds and stereocenters in a single operation. However, despite the great importance of substituted cyclopentanes, given their prevalence in complex natural products and pharmaceutical agents, the rapid, enantioselective assembly of these carbocycles lags behind cyclohexanes. Herein, we describe a novel Michael-aldol-β-lactonization organocascade process for the synthesis of complex cyclopentanes utilizing chiral α,β-unsaturated acylammonium intermediates, readily generated by activation of commodity unsaturated acid chlorides with chiral isothiourea catalysts. This efficient methodology enables the construction of two C-C bonds, one C-O bond, two rings, and three contiguous stereogenic centers delivering complex cyclopentanes with high levels of relative and absolute stereocontrol. Our results suggest that unsaturated acyl ammonium intermediates have broad utility for the design of organocascade and multicomponent processes with the latter demonstrated by a Michael-Michael-aldol-β-lactonization.

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Section: Resultsmentioning

confidence: 64%

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Liu¹,

Shirley²,

Van³

et al. 2013

Nature Chem

128

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Pyroglutamic Acid in Drug Synthesis, Part 1 A Method for the Synthesis of Enantiomerically Pure 4‐Alkyl‐4‐arylpyroglutamic Acids

Fleischhacker

Riedl

Völlenkle

et al. 1996

Archiv der Pharmazie

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Synthesis of the title compounds is described, starting from alkylation of the pyroglutaminol-acetal 4a"' at the a-lactam position C-6 with methyl iodide. Subsequent addition of 2-cyclohexen-lone led to diastereoselective formation of the 1.2-aldol addition product 7 W c , which after dehydratization was aromatizrd with DDQ to yield the 6-methyl-6-phenyl derivative 7h. Acetal cleavage and Jones oxidation yielded 4,4-disubstituted. enantiomerically pure pyroglutamic acid 3b. X-ray analysis confirmed the assignment of the configuration of the newly created chiral centre. I R5 Figure 1Arch. Phurm. Phnrm. Med. Chem.

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Metallorganische Verbindungen, LIV^1a) Reaktionen von Trialkylaluminium mit Alkalimetallen oder Magnesium und elektronenaffinen Olefinen

Lehmkuhl

Čuljković

Nehl

1973

Justus Liebigs Ann. Chem.

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Elektronenaffine ungesattigte Kohlenwasserstoffe reagieren mit Trialkylaluminium und Alkalimetallen in Ather zu aquimolaren Mischungen von Alkalitetraalkylaluminium 1 und Alkalidialkylaluminium-dihydro-athylen, -styrol 2 und dessen Dimerem 3, -stilben 4 und -butadien 5. Die Tendenz zur at-Komplexbildung steigt mit zunehmender Elektronenaffinitat der Olefine. Daneben wird die Reaktion durch die Solvatationskraft des Losungsmittels und die Ionisierbarkeit des Alkalimetalls beeinflul3t. In Benzol sind Trialkylaluminium-Verbindungen nicht elektrolytisch dissoziiert. Hier entstehen Dialkali-bis(trialkyla1uminium)-dihydro-butadien 6 und -toIan 7. -An Stelle der Alkalimetalle laBt sich auch Magnesium einsetzen. Dies konnte am Beispiel der Reaktionen rnit Isopren, 2,3-Dimethylbutadien, 1,4-Diphenylbutadien und Butadien gezeigt werden. 1,3-Diene lassen sich durch Reaktion rnit Alkalimetall und Trialkylaluminium und nachfolgende Protolyse rnit Triathylamin weitgehend selektiv hydrieren. So erhalt man, ohne dal3 eine Isolierung der komplexen Aluminium-Verbindung notig ist, aus Isopren uberwiegend 2-Methyl-l-buten, aus 1,3-Pentadien 2-Penten und aus 2,3-Dimethyl-butadien 2,3-Dimethyl-l-buten. -An Hand der Reaktionsprodukte wird der Mechanismus der Hydrolyse diskutiert. Danach werden Bindungen zwischen Aluminium und sekundarem Kohlenstoffatom leichter gespalten als solche zwischen Aluminium und primarem Kohlenstoff. In Triathylamin als Solvens verlauft die Hydrolyse etwa doppelt so haufig uber die Bildung von Zwischenstufen rnit 3-Alkenyl-aluminat-Struktur wie iiber solche mit der Struktur eines 2-Alkenyl-aluminats. Organometallic Compounds, LIV. -Reactions of Trialkylaluminium with Alkali Metals or Magnesium and Olefins with High Electron AffinityUnsaturated hydrocarbons of high electron affinity react ]with trialkylaluminium und alkali metals in ether to give equimolar mixtures of alkali metal-tetraalkylaluminium (1) and alkali nietallo(dialkylaluminium) dihydro-ethylene, styrene 2 and its dimer 3, stilbene 4, and 1,3-butadiene 5. The tendency to form complexes increases with the electron affinity of the olefins. Moreover, the reaction is influenced by the solvation strength of the solvent and the ionisation potential of the alkali metal. In benzene, trialkylaluminiums are not dissociated into ions. In this case, di(alka1i metallo)-bis(trialky1aluminium)dihydro-butadiene 6 and tolane 7 are formed. -It is possible to use magnesium instead of alkali metals. This has been shown by reactions with isoprene, 2,3-dimethylbutadiene, and butadiene. 1,3-Diolefins can be hydrogenated in a largely selective manner by reaction with alkali metal and tridlkylalu-

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Methods for Total Synthesis of Steroids. XVIII.¹ Δ¹⁴ -16-Keto Steroid Approach to Ring D. H.² Introduction of 17-Carboxy Group. Synthesis of 14α,17β and 14β,17α Isomers of rac-Estra-5(10),6,8-triene-17-carboxylic Acid

Cited by 7 publications

References 1 publication

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Pyroglutamic Acid in Drug Synthesis, Part 1 A Method for the Synthesis of Enantiomerically Pure 4‐Alkyl‐4‐arylpyroglutamic Acids

Metallorganische Verbindungen, LIV^1a) Reaktionen von Trialkylaluminium mit Alkalimetallen oder Magnesium und elektronenaffinen Olefinen

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Methods for Total Synthesis of Steroids. XVIII.1 Δ14 -16-Keto Steroid Approach to Ring D. H.2 Introduction of 17-Carboxy Group. Synthesis of 14α,17β and 14β,17α Isomers of rac-Estra-5(10),6,8-triene-17-carboxylic Acid

Cited by 7 publications

References 1 publication

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Pyroglutamic Acid in Drug Synthesis, Part 1 A Method for the Synthesis of Enantiomerically Pure 4‐Alkyl‐4‐arylpyroglutamic Acids

Metallorganische Verbindungen, LIV1a) Reaktionen von Trialkylaluminium mit Alkalimetallen oder Magnesium und elektronenaffinen Olefinen

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Methods for Total Synthesis of Steroids. XVIII.¹ Δ¹⁴ -16-Keto Steroid Approach to Ring D. H.² Introduction of 17-Carboxy Group. Synthesis of 14α,17β and 14β,17α Isomers of rac-Estra-5(10),6,8-triene-17-carboxylic Acid

Metallorganische Verbindungen, LIV^1a) Reaktionen von Trialkylaluminium mit Alkalimetallen oder Magnesium und elektronenaffinen Olefinen