Tom Livinghouse - Cochemist

1,2-Disubstituted Alkenes as Migratory Insertion Participants in Zn(II)-Promoted Metalloamination/Cyclization of N,N-Dimethylhydrazinoalkenes

Co-reporter:Bryce Sunsdahl, Ky Mickelsen, Sean Zabawa, Bryon K. Anderson, and Tom Livinghouse

The Journal of Organic Chemistry 2016 Volume 81(Issue 21) pp:10160-10164

Publication Date(Web):July 25, 2016

DOI:10.1021/acs.joc.6b01328

Diethylzinc-mediated metalloamination/cyclization of unsaturated N,N-dimethylhydrazines has been extended to the use of 1,2-disubstituted alkenes as N–Zn migratory insertion acceptors. Representative 2-arylethenes and vinylcyclopropanes readily serve as reaction participants in metalloamination/cyclization–allylation cascades.

Divergent Stereocontrolled Synthesis of the Enantiopure Tetracyclic Cores of Asparagamine A and Stemofoline via an Intramolecular 2-Propylidine-1,3-(bis)silane Bicyclization

Co-reporter:Bryon K. Anderson and Tom Livinghouse

The Journal of Organic Chemistry 2015 Volume 80(Issue 20) pp:9847-9855

Publication Date(Web):September 11, 2015

DOI:10.1021/acs.joc.5b01625

A concise and highly diastereoselective synthesis of the polyfused tetracyclic cores of the Stemona alkaloids asparagamine A and stemofoline that relies on a 2-propylidine-1,3-(bis)silane bicyclization onto a enantiodefined pyrrolidine 2,5-di(cation) equivalent derived from l-malic acid is reported. A crucial feature of this divergent synthetic approach involves the solvolysis of a transient and highly labile tertiary-propargylic hydroxylactam trifluoroacetate in the strongly ionizing medium 5 M LiClO4/Et2O. The acyliminium ion generated in this manner undergoes stereospecific interception by the aforementioned (bis)silane nucleophile.

Frontispiz: Intramolecular Metalloamination of N,N-Dimethylhydrazinoalkenes: A Versatile Method to Access Functionalized Piperidines and Pyrrolidines

Co-reporter:Bryce Sunsdahl;Adrian R. Smith ;Dr. Tom Livinghouse

Angewandte Chemie 2014 Volume 126( Issue 52) pp:

Publication Date(Web):

DOI:10.1002/ange.201485261

Intramolecular Metalloamination of N,N-Dimethylhydrazinoalkenes: A Versatile Method to Access Functionalized Piperidines and Pyrrolidines

Co-reporter:Bryce Sunsdahl;Adrian R. Smith ;Dr. Tom Livinghouse

Angewandte Chemie 2014 Volume 126( Issue 52) pp:14580-14584

Publication Date(Web):

DOI:10.1002/ange.201407768

Abstract

Highly diastereoselective metalloamination/cyclization reactions of zinc(II) hydrazides obtained through reaction of diethylzinc with N,N-dimethylhydrazinoalkenes are described. The resulting organozinc intermediates undergo facile allylation and acylation, in situ, to provide the corresponding functionalized piperidines and pyrrolidines.

Intramolecular Metalloamination of N,N-Dimethylhydrazinoalkenes: A Versatile Method to Access Functionalized Piperidines and Pyrrolidines

Co-reporter:Bryce Sunsdahl;Adrian R. Smith ;Dr. Tom Livinghouse

Angewandte Chemie International Edition 2014 Volume 53( Issue 52) pp:14352-14356

Publication Date(Web):

DOI:10.1002/anie.201407768

Abstract

Highly diastereoselective metalloamination/cyclization reactions of zinc(II) hydrazides obtained through reaction of diethylzinc with N,N-dimethylhydrazinoalkenes are described. The resulting organozinc intermediates undergo facile allylation and acylation, in situ, to provide the corresponding functionalized piperidines and pyrrolidines.

Frontispiece: Intramolecular Metalloamination of N,N-Dimethylhydrazinoalkenes: A Versatile Method to Access Functionalized Piperidines and Pyrrolidines

Co-reporter:Bryce Sunsdahl;Adrian R. Smith ;Dr. Tom Livinghouse

Angewandte Chemie International Edition 2014 Volume 53( Issue 52) pp:

Publication Date(Web):

DOI:10.1002/anie.201485261

Rapid and Efficient Procedure for the Synthesis of Group 3 Metal Tris[bis(dimethylsilyl)amide] THF Complexes

Co-reporter:Adrian R. Smith and Tom Livinghouse

Organometallics 2013 Volume 32(Issue 5) pp:1528-1530

Publication Date(Web):October 31, 2012

DOI:10.1021/om3006849

An expedient method for the synthesis of group 3 metal tris[bis(dimethylsilyl)amide] THF complexes from the corresponding tris[bis(trimethylsilyl)amide]s is described. Advantages of this technique over previous methods include short reaction times, simple workup, and near-quantitative yields that require only commercially available reagents.

Donor ligand effects in group 3 metal-catalyzed hydroaminations

Co-reporter:Adrian R. Smith, Helena M. Lovick, Tom Livinghouse

Tetrahedron Letters 2012 Volume 53(Issue 47) pp:6358-6360

Publication Date(Web):21 November 2012

DOI:10.1016/j.tetlet.2012.09.019

A series of donor ligands were examined for their effect on group 3 metal-catalyzed intramolecular alkene hydroamination. The cyclization proved to be surprisingly tolerant to the presence of several coordinative functional groups suggesting more latitude with regard to reaction conditions of group 3 metal-catalyzed processes.

On the stereoselective bicyclization of aminodienes catalyzed by chelating diamide complexes of the group 3 metals. A direct comparison of Sc(III) and Y(III) bis(amide)s with an application to the synthesis of alkaloid 195F

Co-reporter:Tao Jiang, Tom Livinghouse and Helena M. Lovick

Chemical Communications 2011 vol. 47(Issue 48) pp:12861-12863

Publication Date(Web):02 Nov 2011

DOI:10.1039/C1CC15399D

Highly diastereoselective bicyclizations of aminodienes catalyzed by chelating diamide complexes of Sc(III) and Y(III) that lead to pyrrolizidines and indolizidines are described. This bis(annulation) procedure has been utilized in a concise synthesis of the pyrrolizidine alkaloid 195F.

Structure–activity relationships in group 3 metal catalysts for asymmetric intramolecular alkene hydroamination. An investigation of ligands based on the axially chiral 1,1′-binaphthyl-2,2′-diamine motif

Co-reporter:Helena M. Lovick, Duk K. An and Thomas S. Livinghouse

Dalton Transactions 2011 vol. 40(Issue 30) pp:7697-7700

Publication Date(Web):28 Jun 2011

DOI:10.1039/C1DT10222B

From a series of N,N′-disubstituted-1,1′-binaphthyl-2,2′-diamines, several group 3 metal complexes were synthesized via an in situ procedure. These chiral complexes were subsequently applied to catalysis of intramolecular alkene hydroamination. Significant structure–activity relationships were observed, most notably a reversal of stereoselectivity for cyclopentylversusdiphenylmethyl substituents.

A Stereocontrolled Synthesis of (±)-Xenovenine via a Scandium(III)-Catalyzed Internal Aminodiene Bicyclization Terminated by a 2-(5-Ethyl-2-thienyl)ethenyl Group

Co-reporter:Tao Jiang and Tom Livinghouse

Organic Letters 2010 Volume 12(Issue 19) pp:4271-4273

Publication Date(Web):September 2, 2010

DOI:10.1021/ol101646t

A highly diastereoselective binary hydroamination of a 5-amino-1,8-diene containing a 2-(5-ethyl-2-thienyl)ethenyl terminator has been utilized in an efficient synthesis of (±)-xenovenine (1). A pronounced rate enhancement was observed for cyclization onto the 2-(heteroaromatic)ethenyl group in comparison to a simple 1,2-disubstituted alkene.

Yttrium(III)-Catalyzed Intramolecular Alkyne Hydroaminations

Co-reporter:Hyunseok Kim;Jun Hwan Shim;Seong Guk Lee;Phil Ho Lee

Advanced Synthesis & Catalysis 2006 Volume 348(Issue 6) pp:

Publication Date(Web):5 APR 2006

DOI:10.1002/adsc.200505448

The neutral Y(III) complex 4 has been shown to be an effective precatalyst for intramolecular alkyne hydroaminations that provide cyclic amines in good to excellent yields.

Internal Alkene Hydroaminations Catalyzed by Zirconium(IV) Complexes and Asymmetric Alkene Hydroaminations Catalyzed by Yttrium(III) Complexes

Co-reporter:Hyunseok Kim;Young Kwan Kim;Jun Hwan Shim;Misook Kim;Mijung Han;Phil Ho Lee

Advanced Synthesis & Catalysis 2006 Volume 348(Issue 18) pp:

Publication Date(Web):15 DEC 2006

DOI:10.1002/adsc.200606171

The thiophosphinic amide 2 was prepared in 68 % yield by the reaction of 2,2-dimethyl-1,3-propanediamine with diisopropylchlorophosphine followed by the addition of sulfur. Attachment of the proligand 2 to zirconium was achieved by direct metalation with Zr(NMe₂)₄ in benzene-d₆ or toluene-d₈ to afford complex 3via elimination of dimethylamine. The neutral Zr(IV) complex 3 has been shown to be an effective precatalyst for intramolecular alkene hydroaminations that provide cyclic amines in good to excellent yields. A variety of chiral ligands (20, 22, 24, and 25–30) were prepared for asymmetric internal alkene hydroaminations. Metalation of chiral ligands to yttrium was accomplished with Y[N(TMS)₂]₃ in benzene-d₆ or toluene-d₈ to give complexes. Treatment of 7 with 5 mol % of 33 in benzene-d₆ (25 °C, 18 h) or toluene-d₈ (25 °C, 15 h) afforded 2,4,4-trimethylpyrrolidine 14 in 95 % yield (61 % ee).

Intramolecular alkene hydroaminations catalyzed by a bis(thiophosphinic amidate) Zr(IV) complex

Co-reporter:Hyunseok Kim, Phil Ho Lee and Tom Livinghouse

Chemical Communications 2005 (Issue 41) pp:5205-5207

Publication Date(Web):20 Sep 2005

DOI:10.1039/B505738H

A neutral Zr(IV) complex has been shown to be an effective precatalyst for intramolecular alkene hydroaminations that provide cyclic amines in good to excellent yields.

Exceptional Rate Enhancements and Improved Diastereoselectivities through Chelating Diamide Coordination in Intramolecular Alkene Hydroaminations Catalyzed by Yttrium and Neodymium Amido Complexes

Co-reporter:Young Kwan Kim Dr.

Angewandte Chemie 2002 Volume 114(Issue 22) pp:

Publication Date(Web):12 NOV 2002

DOI:10.1002/1521-3757(20021115)114:22<4344::AID-ANGE11114344>3.0.CO;2-7

Exceptional Rate Enhancements and Improved Diastereoselectivities through Chelating Diamide Coordination in Intramolecular Alkene Hydroaminations Catalyzed by Yttrium and Neodymium Amido Complexes

Co-reporter:Young Kwan Kim Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 19) pp:

Publication Date(Web):4 OCT 2002

DOI:10.1002/1521-3773(20021004)41:19<3645::AID-ANIE3645>3.0.CO;2-F

Modification of the metal center in the complexes [Ln{N(TMS)₂}₃] (Ln=Y, Nd; TMS=trimethylsilyl) is readily achieved by amine elimination in the presence of sterically hindered chelating diamines to provide complexes with substantially augmented catalytic activities and improved stereoselectivities in intramolecular alkene hydroamination (see scheme).

Exceptional Rate Enhancements and Improved Diastereoselectivities through Chelating Diamide Coordination in Intramolecular Alkene Hydroaminations Catalyzed by Yttrium and Neodymium Amido Complexes

Co-reporter:Young Kwan Kim Dr.

Angewandte Chemie International Edition 2002 Volume 41(Issue 22) pp:

Publication Date(Web):12 NOV 2002

DOI:10.1002/1521-3773(20021115)41:22<4170::AID-ANIE11114170>3.0.CO;2-L

Exceptional Rate Enhancements and Improved Diastereoselectivities through Chelating Diamide Coordination in Intramolecular Alkene Hydroaminations Catalyzed by Yttrium and Neodymium Amido Complexes

Co-reporter:Young Kwan Kim Dr.

Angewandte Chemie 2002 Volume 114(Issue 19) pp:

Publication Date(Web):4 OCT 2002

DOI:10.1002/1521-3757(20021004)114:19<3797::AID-ANGE3797>3.0.CO;2-5

Eine Modifizierung am Metallzentrum der Komplexe [Ln{N(TMS)₂}₃] (Ln=Y, Nd; TMS=Trimethylsilyl) wird leicht erreicht durch Amin-Eliminierung in Gegenwart sterisch gehinderter Diamin-Chelatbildner und führt zu Komplexen mit deutlich erhöhter katalytischer Aktivität und verbesserter Diastereoselektivität bei der intramolekularen Hydroaminierung von Alkenen (siehe Schema).

On the stereoselective bicyclization of aminodienes catalyzed by chelating diamide complexes of the group 3 metals. A direct comparison of Sc(III) and Y(III) bis(amide)s with an application to the synthesis of alkaloid 195F

Co-reporter:Tao Jiang, Tom Livinghouse and Helena M. Lovick

Chemical Communications 2011 - vol. 47(Issue 48) pp:NaN12863-12863

Publication Date(Web):2011/11/02

DOI:10.1039/C1CC15399D

Highly diastereoselective bicyclizations of aminodienes catalyzed by chelating diamide complexes of Sc(III) and Y(III) that lead to pyrrolizidines and indolizidines are described. This bis(annulation) procedure has been utilized in a concise synthesis of the pyrrolizidine alkaloid 195F.

Structure–activity relationships in group 3 metal catalysts for asymmetric intramolecular alkene hydroamination. An investigation of ligands based on the axially chiral 1,1′-binaphthyl-2,2′-diamine motif

Co-reporter:Helena M. Lovick, Duk K. An and Thomas S. Livinghouse

Dalton Transactions 2011 - vol. 40(Issue 30) pp:NaN7700-7700

Publication Date(Web):2011/06/28

DOI:10.1039/C1DT10222B

From a series of N,N′-disubstituted-1,1′-binaphthyl-2,2′-diamines, several group 3 metal complexes were synthesized via an in situ procedure. These chiral complexes were subsequently applied to catalysis of intramolecular alkene hydroamination. Significant structure–activity relationships were observed, most notably a reversal of stereoselectivity for cyclopentylversusdiphenylmethyl substituents.