Organolanthanide-Catalyzed Intramolecular Hydroamination/Cyclization/Bicyclization of Sterically Encumbered Substrates. Scope, Selectivity, and Catalyst Thermal Stability for Amine-Tethered Unactivated 1,2-Disubstituted Alkenes

Jae Sang Ryu, Tobin J Marks, Frank E. McDonald

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Abstract

This paper reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines using coordinatively unsaturated complexes of the type (η5-Me5C5)2LnCH(TMS)2 (Ln = La, Sm), [Me2Si(η5-Me4C5) 2]SmCH(TMS)2, and [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In addition, chiral C 1-symmetric organolanthanide catalysts of the type [Me 2Si(OHF)(CpR*)]LnN(TMS)2 (OHF = η 5-octahydrofluorenyl; Cp = η5-C5H 3; R* = (-)-menthyl; Ln = Sm, Y), and [Me2Si(η 5-Me4C5)(CpR*)]SmN(TMS)2 (Cp = η5-H3C5; R* = (-)-menthyl) mediate asymmetric intramolecular hydroamination/cyclization of amines bearing internal olefins and afford chiral 2-substituted piperidine and pyrrolidine in enantioselectivities as high as 84:16 er at 60 °C. The substrate of the structure NH2CH2CMe2CH2CH=CH(CH 2)2CH=CH2 is regiospecifically bicyclized by [Me2Si(η5-Me4C5)( tBuN)]LnE(TMS)2 to the corresponding indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of (η 5-Me5C5)2LaCH(TMS)2 in cyclohexane-d12 at 120 °C rapidly releases CH 2(SiMe3)2 and leads to possible formation of fulvene (η6-Me4C5CH2-) species. The thermolysis product readily reverts to active catalysts upon protonolysis by substrate and exhibits the same catalytic activity as the (η 51-Me5C5) 2LaCH(TMS)2 precatalyst at 120 °C in the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active lanthanide-amido complexes (η5-Me5C5) 2La(NHR)(NH2R)n and [Me2Si(η 5-Me4C5)(tBuN)]Sm(NHR)(NH 2R)n are shown to be thermally robust species.

Original languageEnglish
Pages (from-to)1038-1052
Number of pages15
JournalJournal of Organic Chemistry
Volume69
Issue number4
DOIs
Publication statusPublished - Feb 20 2004

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Catalyst selectivity
Cyclization
Alkenes
Amines
Thermodynamic stability
Pyrrolidines
Thermolysis
Catalysts
Substrates
Bearings (structural)
Indolizidines
Piperidines
Lanthanoid Series Elements
Enantioselectivity
Catalyst activity

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

@article{60f7e040cf8449569f53c2855fcb844f,
title = "Organolanthanide-Catalyzed Intramolecular Hydroamination/Cyclization/Bicyclization of Sterically Encumbered Substrates. Scope, Selectivity, and Catalyst Thermal Stability for Amine-Tethered Unactivated 1,2-Disubstituted Alkenes",
abstract = "This paper reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines using coordinatively unsaturated complexes of the type (η5-Me5C5)2LnCH(TMS)2 (Ln = La, Sm), [Me2Si(η5-Me4C5) 2]SmCH(TMS)2, and [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In addition, chiral C 1-symmetric organolanthanide catalysts of the type [Me 2Si(OHF)(CpR*)]LnN(TMS)2 (OHF = η 5-octahydrofluorenyl; Cp = η5-C5H 3; R* = (-)-menthyl; Ln = Sm, Y), and [Me2Si(η 5-Me4C5)(CpR*)]SmN(TMS)2 (Cp = η5-H3C5; R* = (-)-menthyl) mediate asymmetric intramolecular hydroamination/cyclization of amines bearing internal olefins and afford chiral 2-substituted piperidine and pyrrolidine in enantioselectivities as high as 84:16 er at 60 °C. The substrate of the structure NH2CH2CMe2CH2CH=CH(CH 2)2CH=CH2 is regiospecifically bicyclized by [Me2Si(η5-Me4C5)( tBuN)]LnE(TMS)2 to the corresponding indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of (η 5-Me5C5)2LaCH(TMS)2 in cyclohexane-d12 at 120 °C rapidly releases CH 2(SiMe3)2 and leads to possible formation of fulvene (η6-Me4C5CH2-) species. The thermolysis product readily reverts to active catalysts upon protonolysis by substrate and exhibits the same catalytic activity as the (η 5,η1-Me5C5) 2LaCH(TMS)2 precatalyst at 120 °C in the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active lanthanide-amido complexes (η5-Me5C5) 2La(NHR)(NH2R)n and [Me2Si(η 5-Me4C5)(tBuN)]Sm(NHR)(NH 2R)n are shown to be thermally robust species.",
author = "Ryu, {Jae Sang} and Marks, {Tobin J} and McDonald, {Frank E.}",
year = "2004",
month = "2",
day = "20",
doi = "10.1021/jo035417c",
language = "English",
volume = "69",
pages = "1038--1052",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Organolanthanide-Catalyzed Intramolecular Hydroamination/Cyclization/Bicyclization of Sterically Encumbered Substrates. Scope, Selectivity, and Catalyst Thermal Stability for Amine-Tethered Unactivated 1,2-Disubstituted Alkenes

AU - Ryu, Jae Sang

AU - Marks, Tobin J

AU - McDonald, Frank E.

PY - 2004/2/20

Y1 - 2004/2/20

N2 - This paper reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines using coordinatively unsaturated complexes of the type (η5-Me5C5)2LnCH(TMS)2 (Ln = La, Sm), [Me2Si(η5-Me4C5) 2]SmCH(TMS)2, and [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In addition, chiral C 1-symmetric organolanthanide catalysts of the type [Me 2Si(OHF)(CpR*)]LnN(TMS)2 (OHF = η 5-octahydrofluorenyl; Cp = η5-C5H 3; R* = (-)-menthyl; Ln = Sm, Y), and [Me2Si(η 5-Me4C5)(CpR*)]SmN(TMS)2 (Cp = η5-H3C5; R* = (-)-menthyl) mediate asymmetric intramolecular hydroamination/cyclization of amines bearing internal olefins and afford chiral 2-substituted piperidine and pyrrolidine in enantioselectivities as high as 84:16 er at 60 °C. The substrate of the structure NH2CH2CMe2CH2CH=CH(CH 2)2CH=CH2 is regiospecifically bicyclized by [Me2Si(η5-Me4C5)( tBuN)]LnE(TMS)2 to the corresponding indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of (η 5-Me5C5)2LaCH(TMS)2 in cyclohexane-d12 at 120 °C rapidly releases CH 2(SiMe3)2 and leads to possible formation of fulvene (η6-Me4C5CH2-) species. The thermolysis product readily reverts to active catalysts upon protonolysis by substrate and exhibits the same catalytic activity as the (η 5,η1-Me5C5) 2LaCH(TMS)2 precatalyst at 120 °C in the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active lanthanide-amido complexes (η5-Me5C5) 2La(NHR)(NH2R)n and [Me2Si(η 5-Me4C5)(tBuN)]Sm(NHR)(NH 2R)n are shown to be thermally robust species.

AB - This paper reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines using coordinatively unsaturated complexes of the type (η5-Me5C5)2LnCH(TMS)2 (Ln = La, Sm), [Me2Si(η5-Me4C5) 2]SmCH(TMS)2, and [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me2Si(η 5-Me4C5)(tBuN)]LnE(TMS)2 mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In addition, chiral C 1-symmetric organolanthanide catalysts of the type [Me 2Si(OHF)(CpR*)]LnN(TMS)2 (OHF = η 5-octahydrofluorenyl; Cp = η5-C5H 3; R* = (-)-menthyl; Ln = Sm, Y), and [Me2Si(η 5-Me4C5)(CpR*)]SmN(TMS)2 (Cp = η5-H3C5; R* = (-)-menthyl) mediate asymmetric intramolecular hydroamination/cyclization of amines bearing internal olefins and afford chiral 2-substituted piperidine and pyrrolidine in enantioselectivities as high as 84:16 er at 60 °C. The substrate of the structure NH2CH2CMe2CH2CH=CH(CH 2)2CH=CH2 is regiospecifically bicyclized by [Me2Si(η5-Me4C5)( tBuN)]LnE(TMS)2 to the corresponding indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of (η 5-Me5C5)2LaCH(TMS)2 in cyclohexane-d12 at 120 °C rapidly releases CH 2(SiMe3)2 and leads to possible formation of fulvene (η6-Me4C5CH2-) species. The thermolysis product readily reverts to active catalysts upon protonolysis by substrate and exhibits the same catalytic activity as the (η 5,η1-Me5C5) 2LaCH(TMS)2 precatalyst at 120 °C in the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active lanthanide-amido complexes (η5-Me5C5) 2La(NHR)(NH2R)n and [Me2Si(η 5-Me4C5)(tBuN)]Sm(NHR)(NH 2R)n are shown to be thermally robust species.

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