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Palladium-catalyzed cyclization strategies :Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Palladium-catalyzed cyclization strategies :
Reminder of title:	Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482.
Author:	Ameriks, Michael Kenneth.
Description:	431 p.
Notes:	Adviser: Barry M. Trost.
Notes:	Source: Dissertation Abstracts International, Volume: 64-03, Section: B, page: 1243.
Contained By:	Dissertation Abstracts International64-03B.
Subject:	Chemistry, Organic.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3085157
ISBN:	0496329642

Palladium-catalyzed cyclization strategies :Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482.
Ameriks, Michael Kenneth.

Palladium-catalyzed cyclization strategies :Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482. [electronic resource] - 431 p.

Adviser: Barry M. Trost.

Thesis (Ph.D.)--Stanford University, 2003.

A successful synthesis of the benzazocine core of FR-900482 was achieved by employing a palladium-catalyzed carbonylative lactamization. The cylization precursors could be obtained in high enantiopurity by an ephedrine-mediated zinc-alkynylide addition to a highly enolizable arylacetaldehyde. The carbonylative cyclization was tolerant of electron-donating and electron-withdrawing groups on the aromatic ring, and both anilines and aryl hydroxylamines functioned as nitrogen nucleophiles. Despite the structural similarity of the lactam products to benzazocines utilized by other group in syntheses of the mitomycins and FR-900482, several attempted oxidations of the olefin in the 8-membered lactam proved fruitless.

ISBN: 0496329642Subjects--Topical Terms:

193634
Chemistry, Organic.

Palladium-catalyzed cyclization strategies :Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482.
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245 1 0 $a Palladium-catalyzed cyclization strategies : $b Application to the synthesis of tetrahydroquinolines and the benzazocine core of FR-900482. $h [electronic resource]
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500 $a Source: Dissertation Abstracts International, Volume: 64-03, Section: B, page: 1243.
502 $a Thesis (Ph.D.)--Stanford University, 2003.
520 # $a A successful synthesis of the benzazocine core of FR-900482 was achieved by employing a palladium-catalyzed carbonylative lactamization. The cylization precursors could be obtained in high enantiopurity by an ephedrine-mediated zinc-alkynylide addition to a highly enolizable arylacetaldehyde. The carbonylative cyclization was tolerant of electron-donating and electron-withdrawing groups on the aromatic ring, and both anilines and aryl hydroxylamines functioned as nitrogen nucleophiles. Despite the structural similarity of the lactam products to benzazocines utilized by other group in syntheses of the mitomycins and FR-900482, several attempted oxidations of the olefin in the 8-membered lactam proved fruitless.
520 # $a In order to circumvent the regiochemical problems associated with tetrahydroquinoline formation, three alternative strategies for forming the benzazocine core of FR-900482 were examined: (1) a [2,3] N,O-sigmatropic rearrangement of a benzoxazepine (2) an intramolecular nitrosoarene ene reaction, and (3) a palladium-catalyzed carbonylative lactamization. Although the first two approaches failed to provide the desired 8-membered rings, several novel synthetic methods were developed during these studies. Specifically, a diastereoselective fluoride-induced 7-endo cyclization of a vinyl epoxide with a tethered hydroxamic acid provided a functionalized benzoxazepine. The same benzoxazepine could be formed as a mixture of diastereomers from a palladium-catalyzed 7-exo cyclization of a hydroxamic acid onto a pi-allyl intermediate generated from a vinyl epoxide.
520 # $a With the central goal of developing novel methodology for the construction of alkaloids containing medium-sized rings, we investigated several synthetic approaches to the antitumor agent FR-900482. Initial studies focused on controlling the regioselectivity of intramolecular aminations of pi-allylpalladium intermediates generated in two ways: (1) the hydropalladation of terminal allenes, and (2) the ionization of allylic carbonates. Both approaches provided only tetrahydroquinoline products through a 6-exo cyclization. In the presence of a catalyst system comprised of 5% [{Pd(C3H 5)Cl}2], 12% dppf, and 20% acetic acid, aminoallenes constructed in 8 or 9 steps from 3,5-dinitro-p-toluic acid underwent a smooth cyclization in dioxane at 100°C to form 2,3-cis-tetrahydroquinolines in high yield (94%) and diastereoselectivity (12:1). Similarly, anilines with tethered (Z)-allylic carbonates (assembled in 13 steps from 5-nitrovanillin) produced 2,3,4-trisubstituted tetrahydroquinolines in high yield (86%) and diastereoselectivity (>95:5) when exposed to a catalytic amount of Pd(0) in THF at 65°C.
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