Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanide Complexes. Scope, Diastereo- and Enantioselectivity, and Reaction Mechanism

Sukwon Hong, Amber M. Kawaoka, Tobin J Marks

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Abstract

Organolanthanide complexes of the general type Cp′ 2LnCH(TMS)2 (Cp′ = η5-Me 5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me 4C5)(tBuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-η3 allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative ΔS‡ implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR* )SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 71% ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (±)-pinidine and (+)-coniine from simple diene precursors.

Original languageEnglish
Pages (from-to)15878-15892
Number of pages15
JournalJournal of the American Chemical Society
Volume125
Issue number51
DOIs
Publication statusPublished - Dec 24 2003

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Enantioselectivity
Cyclization
Competitive Behavior
Pyrrolidines
Piperidines
Alkaloids
Lanthanoid Series Elements
Catalysts
Kinetics
Electronic states
Substrates
Rare earth elements
Amines
Ligation
Inhibition (Psychology)

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

@article{0a5b195d345e45d99cae6363bf6d4736,
title = "Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanide Complexes. Scope, Diastereo- and Enantioselectivity, and Reaction Mechanism",
abstract = "Organolanthanide complexes of the general type Cp′ 2LnCH(TMS)2 (Cp′ = η5-Me 5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me 4C5)(tBuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-η3 allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative ΔS‡ implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80{\%} de) and 2,6-cis-disubstituted piperidines (99{\%} de). Formation of 2-(prop-1-enyl)piperidine using the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR* )SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 71{\%} ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (±)-pinidine and (+)-coniine from simple diene precursors.",
author = "Sukwon Hong and Kawaoka, {Amber M.} and Marks, {Tobin J}",
year = "2003",
month = "12",
day = "24",
doi = "10.1021/ja036266y",
language = "English",
volume = "125",
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journal = "Journal of the American Chemical Society",
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publisher = "American Chemical Society",
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TY - JOUR

T1 - Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanide Complexes. Scope, Diastereo- and Enantioselectivity, and Reaction Mechanism

AU - Hong, Sukwon

AU - Kawaoka, Amber M.

AU - Marks, Tobin J

PY - 2003/12/24

Y1 - 2003/12/24

N2 - Organolanthanide complexes of the general type Cp′ 2LnCH(TMS)2 (Cp′ = η5-Me 5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me 4C5)(tBuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-η3 allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative ΔS‡ implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR* )SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 71% ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (±)-pinidine and (+)-coniine from simple diene precursors.

AB - Organolanthanide complexes of the general type Cp′ 2LnCH(TMS)2 (Cp′ = η5-Me 5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me 4C5)(tBuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-η3 allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative ΔS‡ implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR* )SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 71% ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (±)-pinidine and (+)-coniine from simple diene precursors.

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