John P. Wolfe

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Name: Wolfe, John

Organization: University of Michigan , USA

Department: Department of Chemistry

Title: Professor(PhD)

TOPICS

Organic Chemistry

Asymmetric Synthesis

Chemicals
References

Synthesis of Cyclic Guanidines Bearing N-Arylsulfonyl and N-Cyano Protecting Groups via Pd-Catalyzed Alkene Carboamination Reactions

Co-reporter:Luke J. Peterson, Jingyi Luo, and John P. Wolfe

Organic Letters June 2, 2017 Volume 19(Issue 11) pp:

Publication Date(Web):May 23, 2017

DOI:10.1021/acs.orglett.7b00946

Palladium-catalyzed carboamination reactions of N-allylguanidines bearing cleavable N-cyano or N-arylsulfonyl protecting groups are described. The reactions afford cyclic guanidine products in good yield, and transformations of substrates bearing internal alkenes proceed with high diastereoselectivity. Deuterium labeling studies indicate these transformations proceed via anti-aminopalladation pathways.

Recent Developments in Pd0-Catalyzed Alkene-Carboheterofunctionalization Reactions

Co-reporter:Zachary J. Garlets;Derick R. White; John P. Wolfe

Asian Journal of Organic Chemistry 2017 Volume 6(Issue 6) pp:636-653

Publication Date(Web):2017/06/01

DOI:10.1002/ajoc.201600577

AbstractThis Focus Review summarizes recent developments in palladium-catalyzed alkene carboalkoxylation and carboamination reactions. New synthetic methods that have been reported within the past four years are described, along with mechanistic insights and the influence of reaction mechanism on product stereochemistry. The applications of these transformations to the synthesis of natural products and other biologically relevant compounds are also discussed.

Synthesis of Substituted γ- and δ-Lactams via Pd-Catalyzed Alkene Carboamination Reactions

Co-reporter:Jordan R. Boothe, Yifan Shen, and John P. Wolfe

The Journal of Organic Chemistry 2017 Volume 82(Issue 5) pp:

Publication Date(Web):February 23, 2017

DOI:10.1021/acs.joc.7b00041

The synthesis of substituted γ- and δ-lactams via palladium-catalyzed alkene carboamination reactions between aryl halides and alkenes bearing pendant amides is described. The substrates for these reactions are generated in 1–3 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene.

Synthesis of Cyclic Guanidines via Silver-Catalyzed Intramolecular Alkene Hydroamination Reactions of N-Allylguanidines

Co-reporter:Zachary J. Garlets, Mattia Silvi, and John P. Wolfe

Organic Letters 2016 Volume 18(Issue 10) pp:2331-2334

Publication Date(Web):May 11, 2016

DOI:10.1021/acs.orglett.6b00598

The silver-catalyzed hydroamination of tosyl-protected N-allylguanidines is described. These reactions provide substituted cyclic guanidines in high yields. The reactions are amenable to the construction of quaternary stereocenters as well as both monocyclic and bicyclic guanidine products.

Asymmetric Palladium-Catalyzed Alkene Carboamination Reactions for the Synthesis of Cyclic Sulfamides

Co-reporter:Zachary J. Garlets;Kaia R. Parenti ;Dr. John P. Wolfe

Chemistry - A European Journal 2016 Volume 22( Issue 17) pp:5919-5922

Publication Date(Web):

DOI:10.1002/chem.201600887

Abstract

The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd₂(dba)₃] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction.

Asymmetric Pd-Catalyzed Alkene Carboamination Reactions for the Synthesis of 2-Aminoindane Derivatives

Co-reporter:Derick R. White; Johnathon T. Hutt

Journal of the American Chemical Society 2015 Volume 137(Issue 35) pp:11246-11249

Publication Date(Web):August 27, 2015

DOI:10.1021/jacs.5b07203

A new type of Pd-catalyzed alkene carboamination reaction that provides direct access to enantioenriched 2-aminoindanes from 2-allylphenyltriflate derivatives and aliphatic amines is described. A catalyst generated in situ from Pd(OAc)2 and (S)-tert-butylPHOX provides the functionalized carbocycles in good yield with up to >99:1 er. The transformations occur via a key anti-aminopalladation that involves intermolecular attack of an amine nucleophile on an arylpalladium alkene complex.

Synthesis of Polycyclic Nitrogen Heterocycles via Cascade Pd-Catalyzed Alkene Carboamination/Diels–Alder Reactions

Co-reporter:Derick R. White and John P. Wolfe

Organic Letters 2015 Volume 17(Issue 10) pp:2378-2381

Publication Date(Web):May 6, 2015

DOI:10.1021/acs.orglett.5b00896

Cascade Pd-catalyzed alkene carboamination/Diels–Alder reactions between bromodienes and amines bearing two pendant alkenes are described. These transformations generate 4 bonds, 3 rings, and 3–5 stereocenters to afford polycyclic nitrogen heterocycles with high diastereoselectivity.

Palladium-Catalyzed Alkene Carboamination Reactions of Electron-Poor Nitrogen Nucleophiles

Co-reporter:Luke J. Peterson

Advanced Synthesis & Catalysis 2015 Volume 357( Issue 10) pp:2339-2344

Publication Date(Web):

DOI:10.1002/adsc.201500334

Aza-Wittig Rearrangements of N-Benzyl and N-Allyl Glycine Methyl Esters. Discovery of a Surprising Cascade Aza-Wittig Rearrangement/Hydroboration Reaction

Co-reporter:Renata K. Everett and John P. Wolfe

The Journal of Organic Chemistry 2015 Volume 80(Issue 18) pp:9041-9056

Publication Date(Web):September 1, 2015

DOI:10.1021/acs.joc.5b01286

Treatment of N-(arylmethyl)-N-aryl or N-allyl-N-aryl glycine methyl ester derivatives with nBu2BOTf and iPr2NEt effects an aza-Wittig rearrangement that provides N-aryl phenylalanine methyl ester derivatives and N-aryl allylglycine methyl ester derivatives, respectively, in good yield with moderate to good diastereoselectivity. Under similar conditions, analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives. Additionally, N-allyl-N-aryl glycine methyl ester derivatives subjected to similar conditions at elevated temperatures undergo an aza-[2,3]-Wittig rearrangement, followed by a subsequent hydroboration oxidation reaction, to afford substituted amino alcohol products.

Development of Enantioselective Palladium-Catalyzed Alkene Carboalkoxylation Reactions for the Synthesis of Tetrahydrofurans

Co-reporter:Brett A. Hopkins;Zachary J. Garlets ;Dr. John P. Wolfe

Angewandte Chemie International Edition 2015 Volume 54( Issue 45) pp:13390-13392

Publication Date(Web):

DOI:10.1002/anie.201506884

Abstract

The Pd-catalyzed coupling of γ-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters.

Development of Enantioselective Palladium-Catalyzed Alkene Carboalkoxylation Reactions for the Synthesis of Tetrahydrofurans

Co-reporter:Brett A. Hopkins;Zachary J. Garlets ;Dr. John P. Wolfe

Angewandte Chemie 2015 Volume 127( Issue 45) pp:13588-13590

Publication Date(Web):

DOI:10.1002/ange.201506884

Abstract

Enantioselective synthesis of tetrahydroquinolines, tetrahydroquinoxalines, and tetrahydroisoquinolines via Pd-Catalyzed alkene carboamination reactions

Co-reporter:B. A. Hopkins and J. P. Wolfe

Chemical Science 2014 vol. 5(Issue 12) pp:4840-4844

Publication Date(Web):27 Aug 2014

DOI:10.1039/C4SC01327A

A catalyst composed of Pd2(dba)3 and (S)-Siphos-PE provides excellent results in Pd-catalyzed alkene carboamination reactions between aniline derivatives bearing pendant alkenes and aryl or alkenyl halides. These transformations generate tetrahydroquinolines and tetrahydroquinoxalines that contain quaternary carbon stereocenters with high levels of asymmetric induction. In addition this catalyst also effects the asymmetric synthesis of tetrahydroisoquinolines via related transformations of 2-allylbenzylamines. In contrast to most other approaches to the asymmetric synthesis of these compounds, which frequently involve functional group interconversion or a single C–C or C–N bond-forming event, the carboamination reactions generate both a C–N bond, a C–C bond, and a stereocenter.

Stereocontrolled Synthesis of Bicyclic Sulfamides via Pd-Catalyzed Alkene Carboamination Reactions. Control of 1,3-Asymmetric Induction by Manipulating Mechanistic Pathways

Co-reporter:Nicholas R. Babij, Grace M. McKenna, Ryan M. Fornwald, and John P. Wolfe

Organic Letters 2014 Volume 16(Issue 12) pp:3412-3415

Publication Date(Web):June 11, 2014

DOI:10.1021/ol5015976

A new annulation strategy for the synthesis of trans-bicyclic sulfamides is described. The Pd-catalyzed alkene carboamination reactions of 2-allyl and cis-2,5-diallyl pyrrolidinyl sulfamides with aryl and alkenyl triflates afford the fused bicyclic compounds in good yields and with good diastereoselectivity (up to 13:1 dr). Importantly, by employing reaction conditions that favor an anti-aminopalladation mechanism, the relative stereochemistry between the C3 and C4a stereocenters of the products is reversed relative to related Pd-catalyzed carboamination reactions that proceed via syn-aminopalladation.

Synthesis of Substituted 2-Aminoimidazoles via Pd-Catalyzed Alkyne Carboamination Reactions. Application to the Synthesis of Preclathridine Natural Products

Co-reporter:Blane P. Zavesky, Nicholas R. Babij, and John P. Wolfe

Organic Letters 2014 Volume 16(Issue 18) pp:4952-4955

Publication Date(Web):September 8, 2014

DOI:10.1021/ol502471x

A new method for the synthesis of 2-aminoimidazole products is described. The heterocyclic products are generated in good yields via Pd-catalyzed carboamination reactions of N-propargyl guanidines and aryl triflates. This methodology generates both a C–N and C–C bond during the annulation step and facilitates the rapid construction of 2-aminoimidazole products with different aryl groups. The utility of this methodology was demonstrated in the total synthesis of preclathridine A, preclathridine B, and dorimidazole B from a single intermediate.

Influence of Catalyst Structure and Reaction Conditions on anti- versus syn-Aminopalladation Pathways in Pd-Catalyzed Alkene Carboamination Reactions of N-Allylsulfamides

Co-reporter:Ryan M. Fornwald;Dr. Jonathan A. Fritz;Dr. John P. Wolfe

Chemistry - A European Journal 2014 Volume 20( Issue 28) pp:8782-8790

Publication Date(Web):

DOI:10.1002/chem.201402258

Abstract

The Pd-catalyzed coupling of N-allylsulfamides with aryl and alkenyl triflates to afford cyclic sulfamide products is described. In contrast to other known Pd-catalyzed alkene carboamination reactions, these transformations may be selectively induced to occur by way of either anti- or syn-aminopalladation mechanistic pathways by modifying the catalyst structure and reaction conditions.

Synthesis of Substituted Tetrahydroindoloisoquinoline Derivatives via Intramolecular Pd-Catalyzed Alkene Carboamination Reactions

Co-reporter:Jeremiah Alicea and John P. Wolfe

The Journal of Organic Chemistry 2014 Volume 79(Issue 9) pp:4212-4217

Publication Date(Web):April 11, 2014

DOI:10.1021/jo500470m

Intramolecular Pd-catalyzed alkene carboamination reactions of substituted 2-allyl-N-(2-bromobenzyl)anilines are described. The substrates for these reactions are generated in two steps from readily available 2-allylanilines and 2-bromobenzaldehyde derivatives. The transformations afford substituted tetrahydroindoloisoquinolines, an uncommon class of fused bicyclic heterocycles, in good yield. The mechanism of these transformations is described, and a model that accounts for the observed product stereochemistry is proposed.

Synthesis of Cyclic Guanidines via Pd-Catalyzed Alkene Carboamination

Co-reporter:Blane P. Zavesky, Nicholas R. Babij, Jonathan A. Fritz, and John P. Wolfe

Organic Letters 2013 Volume 15(Issue 21) pp:5420-5423

Publication Date(Web):October 22, 2013

DOI:10.1021/ol402377y

A new approach to the synthesis of substituted 5-membered cyclic guanidines is described. Palladium-catalyzed alkene carboamination reactions between acyclic N-allyl guanidines and aryl or alkenyl halides provide these products in good yield. This method allows access to a number of different cyclic guanidine derivatives in only two steps from readily available allylic amines.

Synthesis of Substituted 3-Hydroxy-2-Furanone Derivatives via an Unusual Enolate Wittig Rearrangement/Alkylative Cyclization Sequence

Co-reporter:Renata K. Everett and John P. Wolfe

Organic Letters 2013 Volume 15(Issue 12) pp:2926-2929

Publication Date(Web):June 11, 2013

DOI:10.1021/ol4009188

Treatment of methyl O-(alkynylmethyl) glycolate derivatives with dialkylboron triflates and Hünig’s base leads to the formation of highly substituted 3-hydroxy-2-furanone derivatives. The transformations appear to proceed via an unusual mechanism involving initial 2,3-Wittig rearrangement of a boron ester enolate followed by an alkylative cyclization reaction that leads to incorporation of an alkyl group from the boron reagent into the product.

Desymmetrization of meso-2,5-Diallylpyrrolidinyl Ureas through Asymmetric Palladium-Catalyzed Carboamination: Stereocontrolled Synthesis of Bicyclic Ureas

Co-reporter:Nicholas R. Babij ; John P. Wolfe

Angewandte Chemie International Edition 2013 Volume 52( Issue 35) pp:9247-9250

Publication Date(Web):

DOI:10.1002/anie.201302720

Desymmetrization of meso-2,5-Diallylpyrrolidinyl Ureas through Asymmetric Palladium-Catalyzed Carboamination: Stereocontrolled Synthesis of Bicyclic Ureas

Co-reporter:Nicholas R. Babij ; John P. Wolfe

Angewandte Chemie 2013 Volume 125( Issue 35) pp:9417-9420

Publication Date(Web):

DOI:10.1002/ange.201302720

Synthesis of chromans viaPd-catalyzed alkene carboetherification reactions

Co-reporter:Amanda F. Ward, Yan Xu and John P. Wolfe

Chemical Communications 2012 vol. 48(Issue 4) pp:609-611

Publication Date(Web):24 Nov 2011

DOI:10.1039/C1CC15880E

A new method for the construction of 2-substituted and 2,2-disubstituted chromans viaPd-catalyzed carboetherification reactions between aryl/alkenyl halides and 2-(but-3-en-1-yl)phenols is described. These reactions effect formation of a C–O bond and a C–C bond to afford the chroman products in good yield, and also provide stereoselective access to tricyclic chroman derivatives.

Intermolecular Gold(I)-Catalyzed Alkyne Carboalkoxylation Reactions for the Multicomponent Assembly of -Alkoxy Ketones

Co-reporter:Danielle M. Schultz;Nicholas R. Babij

Advanced Synthesis & Catalysis 2012 Volume 354( Issue 18) pp:3451-3455

Publication Date(Web):

DOI:10.1002/adsc.201200825

Abstract

A new gold(I)-catalyzed multicomponent synthesis of β-alkoxy ketones from aldehydes, alcohols, and alkynes is described. This atom economical synthesis was achieved through the use of the gold complex (SPhos)AuNTf₂ as a catalyst, and allows for the preparation of a diverse array of β-alkoxy ketone products. Mechanistic studies illustrate that these reactions proceed via gold(I)-catalyzed hydrolysis of the alkyne to an aryl ketone, which then undergoes an aldol reaction with an oxocarbenium ion generated in situ from the aldehyde and alcohol components.

Synthesis of Enantiomerically Enriched Imidazolidin-2-Ones through Asymmetric Palladium-Catalyzed Alkene Carboamination Reactions

Co-reporter:Brett A. Hopkins ;Dr. John P. Wolfe

Angewandte Chemie 2012 Volume 124( Issue 39) pp:10024-10028

Publication Date(Web):

DOI:10.1002/ange.201205233

Synthesis of Enantiomerically Enriched Imidazolidin-2-Ones through Asymmetric Palladium-Catalyzed Alkene Carboamination Reactions

Co-reporter:Brett A. Hopkins ;Dr. John P. Wolfe

Angewandte Chemie International Edition 2012 Volume 51( Issue 39) pp:9886-9890

Publication Date(Web):

DOI:10.1002/anie.201205233

Intramolecular Alkoxycyanation and Alkoxyacylation Reactions: New Types of Alkene Difunctionalizations for the Construction of Oxygen Heterocycles

Co-reporter:Dr. John P. Wolfe

Angewandte Chemie International Edition 2012 Volume 51( Issue 41) pp:10224-10225

Publication Date(Web):

DOI:10.1002/anie.201204470

Asymmetric Total Synthesis of (+)-Merobatzelladine B

Co-reporter:Nicholas R. Babij ; John P. Wolfe

Angewandte Chemie International Edition 2012 Volume 51( Issue 17) pp:4128-4130

Publication Date(Web):

DOI:10.1002/anie.201201001

Asymmetric Total Synthesis of (+)-Merobatzelladine B

Co-reporter:Nicholas R. Babij ; John P. Wolfe

Angewandte Chemie 2012 Volume 124( Issue 17) pp:4204-4206

Publication Date(Web):

DOI:10.1002/ange.201201001

Intramolekulare Alkoxycyanierungen und Alkoxyacylierungen: Neue Alkendifunktionalisierungen fr den Aufbau von Sauerstoffheterocyclen

Co-reporter:Dr. John P. Wolfe

Angewandte Chemie 2012 Volume 124( Issue 41) pp:10370-10371

Publication Date(Web):

DOI:10.1002/ange.201204470

Intramolecular Alkene Carboamination Reactions for the Synthesis of Enantiomerically Enriched Tropane Derivatives

Co-reporter:Danielle M. Schultz and John P. Wolfe

Organic Letters 2011 Volume 13(Issue 11) pp:2962-2965

Publication Date(Web):May 11, 2011

DOI:10.1021/ol201051q

The synthesis of tropane derivatives via intramolecular Pd-catalyzed alkene difunctionalization reactions is described. Enantiopure N-aryl-γ-aminoalkenes bearing an aryl or alkenyl halide adjacent to the amino group were converted to benzo- or cycloalkenyl-fused tropane products in good yield and with no loss of enantiopurity.

Enantioconvergent Synthesis of (+)-Aphanorphine via Asymmetric Pd-Catalyzed Alkene Carboamination

Co-reporter:Duy N. Mai, Brandon R. Rosen, and John P. Wolfe

Organic Letters 2011 Volume 13(Issue 11) pp:2932-2935

Publication Date(Web):May 10, 2011

DOI:10.1021/ol2009895

A concise asymmetric synthesis of (+)-aphanorphine has been achieved via a new enantioconvergent strategy. A racemic γ-aminoalkene derivative is transformed into a 1:1 mixture of enantiomerically enriched diastereomers using an asymmetric Pd-catalyzed carboamination. This mixture is then converted to an enantiomerically enriched protected aphanorphine derivative by a Friedel–Crafts reaction, which generates a quaternary all-carbon stereocenter. The natural product is obtained in three additional steps.

Synthesis of Saturated 1,4-Benzodiazepines via Pd-Catalyzed Carboamination Reactions.

Co-reporter:Joshua D. Neukom, Alvin S. Aquino, and John P. Wolfe

Organic Letters 2011 Volume 13(Issue 9) pp:2196-2199

Publication Date(Web):March 29, 2011

DOI:10.1021/ol200429a

A new synthesis of 1,4-benzodiazepines and 1,4-benzodiazepin-5-ones is reported. The Pd-catalyzed coupling of N-allyl-2-aminobenzylamine derivatives with aryl bromides affords the heterocyclic products in good yield, and substrates bearing allylic methyl groups are transformed to cis-2,3-disubstituted products with >20:1 dr.

Intramolecular Insertion of Alkenes into Pd−N Bonds. Effects of Substrate and Ligand Structure on the Reactivity of (P−P)Pd(Ar)[N(Ar1)(CH2)3CR═CHR′] Complexes

Co-reporter:Joshua D. Neukom, Nicholas S. Perch, and John P. Wolfe

Organometallics 2011 Volume 30(Issue 5) pp:1269-1277

Publication Date(Web):February 3, 2011

DOI:10.1021/om200008t

Studies on the synthesis and reactivity of a series of (P−P)Pd(Ar)[N(Ar1)(CH2)3CR═CHR′] complexes 3 are described. These complexes are transformed to observable (P−P)Pd(Ar)[pyrrolidin-2-ylmethyl] complexes 4 via syn insertion of the pendant alkene into the Pd−N bond. Complexes 4 then undergo C−C bond-forming reductive elimination to yield N-aryl-2-benzylpyrrolidine derivatives 2. Kinetic studies indicate the rates of conversion of 3 to 4 and 4 to 2 are within 1 order of magnitude. The effects of phosphine ligand structure, alkene substitution, and the electronic properties of the Ar and Ar1 groups on reaction rates are reported, as are the results of deuterium isotope effect studies. The mechanism of the aminopalladation step is discussed in detail, and the results of the experiments described in this paper are most consistent with conversion of 3 to 4 via rate-determining ligand displacement followed by fast aminopalladation. These transformations represent rare examples of syn migratory insertion of unactivated alkenes into Pd−N bonds.

Asymmetric Palladium-Catalyzed Carboamination Reactions for the Synthesis of Enantiomerically Enriched 2-(Arylmethyl)- and 2-(Alkenylmethyl)pyrrolidines

Co-reporter:Duy N. Mai

Journal of the American Chemical Society 2010 Volume 132(Issue 35) pp:12157-12159

Publication Date(Web):August 18, 2010

DOI:10.1021/ja106989h

The enantioselective synthesis of 2-(arylmethyl)- and 2-(alkenylmethyl)pyrrolidine derivatives via Pd-catalyzed alkene carboamination reactions is described. These transformations generate enantiomerically enriched products with up to 94% ee from readily available alkenyl or aryl bromides and N-boc-pent-4-enylamines. The application of this method to a concise asymmetric synthesis of (−)-tylophorine is also discussed.

Intramolecular Alkene Aminopalladation Reactions of (dppf)Pd(Ar)[N(Ar1)(CH2)3CH═CH2] Complexes. Insertion of Unactivated Alkenes into Pd−N Bonds

Co-reporter:Joshua D. Neukom ; Nicholas S. Perch

Journal of the American Chemical Society 2010 Volume 132(Issue 18) pp:6276-6277

Publication Date(Web):April 16, 2010

DOI:10.1021/ja9102259

The synthesis of (dppf)Pd(C6H4-p-F)[N(Ar1)(CH2)3CH═CH2] complexes (3), which are thought to be intermediates in Pd-catalyzed alkene carboamination reactions, is described. These complexes undergo syn-migratory insertion of the alkene into the Pd−N bond to yield observable (dppf)palladium(aryl)(pyrrolidin-2-yl-methyl) complexes 6. Reductive elimination from 6 provides 2-benzylpyrrolidine derivatives 4. The rates of conversion of 3 to 6 (k1) and 6 to 4 (k2) were measured and are within 1 order of magnitude of each other. The syn-migratory insertion stereochemistry was confirmed through a deuterium labeling experiment. These are the first examples of syn-migratory insertions of unactivated alkenes into Pd−N bonds of well-defined complexes.

Pd-Catalyzed Carboamination of Oxazolidin-2-ones: A Stereoselective Route to trans-2,5-Disubstituted Pyrrolidines

Co-reporter:Georgia S. Lemen and John P. Wolfe

Organic Letters 2010 Volume 12(Issue 10) pp:2322-2325

Publication Date(Web):April 20, 2010

DOI:10.1021/ol1006828

Palladium-catalyzed carboamination reactions between aryl bromides and 4-(but-3-enyl)-substituted oxazolidin-2-ones are described. These transformations afford bicyclic oxazolidin-2-one derivatives that can be converted to trans-2,5-disubstituted pyrrolidines in one step. The starting materials are easily prepared from amino acid precursors, and products that contain up to three stereocenters are generated with >20:1 dr.

Synthesis of Polycyclic Nitrogen Heterocycles via Alkene Aminopalladation/Carbopalladation Cascade Reactions

Co-reporter:Danielle M. Schultz and John P. Wolfe

Organic Letters 2010 Volume 12(Issue 5) pp:1028-1031

Publication Date(Web):February 8, 2010

DOI:10.1021/ol100033s

A new method for the synthesis of tricyclic nitrogen heterocycles from N,2-diallylaniline derivatives is described. These transformations proceed via sequential alkene aminopalladation of an intermediate LnPd(Ar)(NRR′) species followed by alkene carbopalladation of the resulting LnPd(Ar)(R) complex. Both alkene insertion steps occur in preference to C−N or C−C bond-forming reductive elimination. An unusual 1,3-palladium shift occurs when 2-Allyl-N-(2-vinylphenyl)aniline is employed as substrate, which yields a tetracyclic molecule with three contiguous stereocenters.

Highly Diastereoselective Pd-Catalyzed Carboetherification Reactions of Acyclic Internal Alkenes. Stereoselective Synthesis of Polysubstituted Tetrahydrofurans

Co-reporter:Amanda F. Ward and John P. Wolfe

Organic Letters 2010 Volume 12(Issue 6) pp:1268-1271

Publication Date(Web):February 19, 2010

DOI:10.1021/ol1001472

A highly diastereoselective synthesis of substituted tetrahydrofurans bearing stereocenters at C2 and C1′ via Pd-catalyzed carboetherification reactions of acyclic internal alkenes is described. Use of an improved catalyst composed of Pd2(dba)3/S-Phos provides products with up to >20:1 dr. The stereoselective preparation of tetrahydrofurans containing three stereocenters, including a molecule structurally related to simplakidine A, is also reported.

Asymmetric Tandem Wittig Rearrangement/Mannich Reactions

Co-reporter:NatalieC. Giampietro ;JohnP. Wolfe

Angewandte Chemie International Edition 2010 Volume 49( Issue 16) pp:2922-2924

Publication Date(Web):

DOI:10.1002/anie.201000609

Asymmetric Tandem Wittig Rearrangement/Mannich Reactions

Co-reporter:NatalieC. Giampietro ;JohnP. Wolfe

Angewandte Chemie 2010 Volume 122( Issue 16) pp:2984-2986

Publication Date(Web):

DOI:10.1002/ange.201000609

Use of Aryl Chlorides as Electrophiles in Pd-Catalyzed Alkene Difunctionalization Reactions

Co-reporter:Brandon R. Rosen, Joshua E. Ney and John P. Wolfe

The Journal of Organic Chemistry 2010 Volume 75(Issue 8) pp:2756-2759

Publication Date(Web):March 18, 2010

DOI:10.1021/jo100344k

The development of conditions that allow use of inexpensive aryl chlorides as electrophiles in Pd-catalyzed alkene carboamination and carboetherification reactions is described. A catalyst composed of Pd(OAc)2 and S-Phos minimizes N-arylation of the substrate and prevents formation of mixtures of regioisomeric products. A number of heterocycles, including pyrrolidines, isoxazolidines, tetrahydrofurans, and pyrazolidines, are efficiently generated with this method.

Asymmetric Tandem Wittig Rearrangement/Aldol Reactions

Co-reporter:Natalie C. Giampietro ; Jeff W. Kampf

Journal of the American Chemical Society 2009 Volume 131(Issue 35) pp:12556-12557

Publication Date(Web):August 14, 2009

DOI:10.1021/ja905930s

A new method for the asymmetric synthesis of α-alkyl-α,β-dihydroxy esters that involves tandem Wittig rearrangement/aldol reactions of O-benzyl- or O-allylglycolate esters derived from 2-phenylcyclohexanol is described. This sequence constructs two C−C bonds and two stereocenters, one of which is quaternary, to afford syn diol products with excellent stereocontrol. Cleavage of the chiral auxiliary affords enantiomerically enriched products with up to 95% ee. The application of this method to the preparation of a key intermediate in the synthesis of the antifungal agent alternaric acid is also described.

Synthesis of Fused-Ring and Attached-Ring bis-Tetrahydrofurans via Pd-Catalyzed Carboetherification

Co-reporter:Amanda F. Ward and John P. Wolfe

Organic Letters 2009 Volume 11(Issue 10) pp:2209-2212

Publication Date(Web):April 20, 2009

DOI:10.1021/ol900594h

A five step-synthesis of fused bis-tetrahydrofurans and attached bis-tetrahydrofurans from butadiene diepoxide is described. Two sequential Pd-catalyzed carboetherification reactions between protected 1,2-diols and aryl/alkenyl bromides, each of which form both a C−O bond and a C−C bond, are used to generate the heterocyclic rings with >20:1 dr. Installation of different R1 and R2 groups is achieved in a straightforward fashion through use of different aryl or alkenyl bromide coupling partners.

New Strategy for the Synthesis of Substituted Morpholines

Co-reporter:Matthew L. Leathen, Brandon R. Rosen and John P. Wolfe

The Journal of Organic Chemistry 2009 Volume 74(Issue 14) pp:5107-5110

Publication Date(Web):June 1, 2009

DOI:10.1021/jo9007223

A four-step synthesis of cis-3,5-disubstituted morpholines from enantiomerically pure amino alcohols is described. The key step in the synthesis is a Pd-catalyzed carboamination reaction between a substituted ethanolamine derivative and an aryl or alkenyl bromide. The morpholine products are generated as single stereoisomers in moderate to good yield. This strategy also provides access to fused bicyclic morpholines as well as 2,3- and 2,5-disubstituted products.

Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines

Co-reporter:Josephine S. Nakhla, Danielle M. Schultz, John P. Wolfe

Tetrahedron 2009 65(33) pp: 6549-6570

Publication Date(Web):

DOI:10.1016/j.tet.2009.04.017

Palladium-Catalyzed Carboetherification and Carboamination Reactions of γ-Hydroxy- and γ-Aminoalkenes for the Synthesis of Tetrahydrofurans and Pyrrolidines

Co-reporter:John P. Wolfe

European Journal of Organic Chemistry 2007 Volume 2007(Issue 4) pp:571-582

Publication Date(Web):13 NOV 2006

DOI:10.1002/ejoc.200600767

Substituted tetrahydrofuran and pyrrolidine moieties are displayed in a wide range of interesting biologically active molecules. The Pd-catalyzed carboetherification or carboamination of γ-hydroxy and γ-aminoalkenes is a powerful tool for the construction of these heterocycles, as it is convergent and can allow access to a variety of analogs from a single γ-hydroxy- or γ-aminoalkene starting material. This microreview describes the current state of this field. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Stereoselective Synthesis of Isoxazolidines through Pd-Catalyzed Carboetherification of N-Butenylhydroxylamines

Co-reporter:Michael B. Hay;John P. Wolfe

Angewandte Chemie International Edition 2007 Volume 46(Issue 34) pp:

Publication Date(Web):26 JUL 2007

DOI:10.1002/anie.200701386

Pd ploy to isoxazolidines: Carboetherification reactions of N-butenylhydroxylamines with aryl bromides afford substituted isoxazolidines in good yield with up to >20:1 d.r. These transformations provide a new strategy for the construction of isoxazolidines and allow for the synthesis of isoxazolidine stereoisomers that cannot be prepared with existing methods.

Stereoselective Synthesis of Isoxazolidines through Pd-Catalyzed Carboetherification of N-Butenylhydroxylamines

Co-reporter:Michael B. Hay;John P. Wolfe

Angewandte Chemie 2007 Volume 119(Issue 34) pp:

Publication Date(Web):26 JUL 2007

DOI:10.1002/ange.200701386

Mehr als eine Alternative: Carboveretherungen von N-Butenylhydroxylaminen mit Bromarenen liefern substituierte Isoxazolidine in guten Ausbeuten und bis d.r. >20:1 (siehe Schema). Diese Umsetzungen bilden eine neue Strategie zum Aufbau von Isoxazolidinen und ermöglichen auch die Synthese von Isoxazolidin-Stereoisomeren, die mit herkömmlichen Methoden nicht herstellbar sind.

Synthesis of N-Aryl-2-allylpyrrolidines via Palladium-Catalyzed Carboamination Reactions of γ-(N-Arylamino)alkenes with Vinyl Bromides

Co-reporter:Joshua E. Ney;Michael B. Hay;Qifei Yang;John P. Wolfe

Advanced Synthesis & Catalysis 2005 Volume 347(Issue 11-13) pp:

Publication Date(Web):19 OCT 2005

DOI:10.1002/adsc.200505172

A palladium-catalyzed carboamination reaction of γ-N-arylamino alkenes with vinyl bromides that affords N-aryl-2-allyl pyrrolidines is described. These reactions proceed with high diastereoselectivity for the formation of trans-2,3- and cis-2,5-disubstituted pyrrolidines. Conditions for a tandem N-arylation/carboamination sequence that leads to the formation of an N-aryl-2-allyl pyrrolidine or indoline via the coupling of a primary γ-amino alkene, an aryl bromide, and a vinyl bromide are also reported. The mechanism of the carboamination reactions and the origin of unexpected products that formally derive from rearrangement of the vinyl bromide are discussed.

Palladium-Catalyzed Synthesis of N-Aryl Pyrrolidines from γ-(N-Arylamino) Alkenes: Evidence for Chemoselective Alkene Insertion into PdN Bonds

Co-reporter:Joshua E. Ney

Angewandte Chemie International Edition 2004 Volume 43(Issue 27) pp:

Publication Date(Web):29 JUN 2004

DOI:10.1002/anie.200460060

The formation of a CC and a CN bond in a reaction between γ-(N-arylamino) alkenes and aryl bromides results in the stereoselective synthesis of substituted pyrrolidine derivatives (see scheme). Preliminary studies suggest these reactions proceed by intramolecular alkene insertion into the PdN bond of intermediate [Pd(Ar)(amido)] complexes. dba=dibenzylideneacetone, dppb=1,3-bis(diphenylphosphanyl)butane.

Palladium-Catalyzed Synthesis of N-Aryl Pyrrolidines from γ-(N-Arylamino) Alkenes: Evidence for Chemoselective Alkene Insertion into PdN Bonds

Co-reporter:Joshua E. Ney

Angewandte Chemie 2004 Volume 116(Issue 27) pp:

Publication Date(Web):29 JUN 2004

DOI:10.1002/ange.200460060

Die Bildung einer C-C- und einer C-N-Bindung bei einer Reaktion zwischen γ-N-Arylaminoalkenen und Arylbromiden führt zur stereoselektiven Synthese substituierter Pyrrolidinderivate (siehe Schema). Erste Studien legen nahe, dass diese Reaktionen über eine intramolekulare Alkeninsertion in die Pd-N-Bindung von [Pd(Ar)(amido)]-Intermediaten verlaufen. dba=Dibenzylidenaceton, dppb=1,3-Bis(diphenylphosphanyl)butan.

Synthesis of chromans viaPd-catalyzed alkene carboetherification reactions

Co-reporter:Amanda F. Ward, Yan Xu and John P. Wolfe

Chemical Communications 2012 - vol. 48(Issue 4) pp:NaN611-611

Publication Date(Web):2011/11/24

DOI:10.1039/C1CC15880E

Enantioselective synthesis of tetrahydroquinolines, tetrahydroquinoxalines, and tetrahydroisoquinolines via Pd-Catalyzed alkene carboamination reactions

Co-reporter:B. A. Hopkins and J. P. Wolfe

Chemical Science (2010-Present) 2014 - vol. 5(Issue 12) pp:NaN4844-4844

Publication Date(Web):2014/08/27

DOI:10.1039/C4SC01327A

Synthesis of 2,3-dihydrobenzofurans via the palladium catalyzed carboalkoxylation of 2-allylphenols

Co-reporter:Johnathon T. Hutt and John P. Wolfe

Inorganic Chemistry Frontiers 2016 - vol. 3(Issue 10) pp:NaN1318-1318

Publication Date(Web):2016/08/22

DOI:10.1039/C6QO00215C

A new Pd-catalyzed alkene carboalkoxylation strategy for the preparation of 2,3-dihydrobenzofurans is described. This method effects the coupling of readily available 2-allylphenol derivatives with aryl triflates to generate a wide range of functionalized 2,3-dihydrobenzofurans in good yields and diastereoselectivities (up to >20:1). Use of newly developed reaction conditions that promote anti-heteropalladation of the alkene is essential in order to generate products in high yield.