Publications by authors named "Thomas R Hoye"

130 Publications

Assembly of the Benzenoid Ring as a Core Strategy for Synthesis of the Isoindolinone Natural Products Isohericerin, Erinacerin A, and Sterenin A.

Org Lett 2021 Sep 20. Epub 2021 Sep 20.

Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.

Here we describe the use of the hexadehydro-Diels-Alder (HDDA) reaction for the construction of the isoindolinone scaffold and its application to the synthesis of the title natural products. The key isoindolinone-forming HDDA reaction involved an unprecedented substrate motif in which an amide carbonyl group was conjugated to the 4π 1,3-diyne component. In addition, a dimethylsilyl (-SiMeH) substituent was exploited to trigger a Fleming-Tamao-Kumada oxidation for the installation of an essential phenolic hydroxyl group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c02752DOI Listing
September 2021

Sulfurane [S(IV)]-Mediated Fusion of Benzynes Leads to Helical Dibenzofurans.

J Am Chem Soc 2021 Sep 23;143(34):13501-13506. Epub 2021 Aug 23.

Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.

Here we disclose a sulfurane-mediated method for the formation of dimeric dibenzofuran helicenes via the reaction between diaryl sulfoxides and hexadehydro-Diels-Alder (HDDA) derived benzynes. A variety of S-shaped and U-shaped helicenes were formed under thermal conditions. Both experimental and DFT studies support a sulfur(IV)-based coupling (aka ligand coupling) mechanism involving tetracarbo-ligated S(IV) intermediates undergoing reductive elimination to afford the helicene products. This process involves the de novo generation of five new rings in a single operation and constitutes a new method for the construction of topologically interesting, polycyclic aromatic compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c07187DOI Listing
September 2021

β-Methyl-δ-valerolactone-containing Thermoplastic Poly(ester-amide)s: Synthesis, Mechanical Properties, and Degradation Behavior.

Polym Chem 2021 Mar 25;12(9):1310-1316. Epub 2021 Feb 25.

Department of Chemistry University of Minnesota, 207 Pleasant St. SE, Minneapolis, Minnesota 55455 USA.

Poly(ester-amide)s (PEAs) have been prepared from (glucose-derived) β-methyl-δ-valerolactone (MVL) by reaction of MVL-derived diamidodiols with diacid chlorides in solution to form poly(ester-amide)s having alternating diester-diamide subunits. The PEAs formed by this method exhibit plastic properties and are of sufficiently high molecular weight to be tough, ductile materials (stress at break: 41-53 MPa, strain at break: 530-640%). The length of the methylene linker unit (n = 1,2,3) between amide groups of the diamidodiols affects the Young's modulus; longer linkers reduce the stiffness of the materials. This allows tuning of the properties by judicious choice of precursors. MVL was also converted to a diacid chloride that was then used to prepare a PEA that is 76 wt% MVL-derived. The degradation rates of suspensions of these new PEAs in basic aqueous media were benchmarked and their instability in aqueous acid was also observed. NMR studies were used to detect the hydrolytic degradation products of both these PEAs as well as a structurally simpler analog.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1py00040cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330554PMC
March 2021

Cu(I)-Catalyzed 1,2-Alkynyl-propargylation and -benzylation of Benzyne Derivatives.

Org Lett 2021 Jul 28;23(14):5448-5451. Epub 2021 Jun 28.

Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States.

We report here a three-component, Cu(I)-catalyzed hexadehydro-Diels-Alder (HDDA) benzyne 1,2-difunctionalization reaction. This protocol allowed the introduction of two different carbon-based substituents onto the in situ-generated benzyne. These substituents were terminal monoynes or diynes partnered with propargylic, benzylic, or allylic chlorides. An example of a sequential HDDA reaction is demonstrated using the product of a 1,3-diyne and a propargylic halide, itself a newly created HDDA precursor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392099PMC
July 2021

"Kobayashi Benzynes" as Hexadehydro-Diels-Alder Diynophiles.

Org Lett 2021 05 22;23(9):3349-3353. Epub 2021 Apr 22.

Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.

We report here elaboration of a cascade strategy for naphthyne formation using Kobayashi benzynes as diynophiles in a subsequent in situ hexadehydro-Diels-Alder reaction. Density functional theory computations suggest that the strained benzynes act as "super-diynophiles" in this transformation. The reaction requires only mildly basic and ambient temperature conditions and allows for rapid construction of various naphthalenic products. The trapping efficiencies of several arynophiles were determined using the benzyne to naphthyne cyclization as an internal clock reaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391086PMC
May 2021

Arylhydrazine Trapping of Benzynes: Mechanistic Insights and a Route to Azoarenes.

Org Lett 2021 05 19;23(9):3432-3436. Epub 2021 Apr 19.

Department of Chemistry, University of Minnesota, 207 Pleasant Street, Southeast, Minneapolis, Minnesota 55455 United States.

Arylhydrazines (ArNHNH) are ambident nucleophiles. We describe here their reactivity with benzynes generated in situ by thermal cyclization of several multiynes. Products arising from attack of both the alpha- and beta-nitrogen atoms are observed. These competitive modes of reaction were explored by DFT calculations. Substituent effects on the site-selectivity for several substituted phenylhydrazines were explored. Interestingly, the hydrazo products from beta-attack (ArNHNHAr') can be oxidized, sometimes in situ by oxygen alone, to give structurally complex, unsymmetrical azoarenes (ArN═NAr'). Toluenesulfonohydrazide and benzohydrazide analogues were each demonstrated to undergo similar transformations, including oxidation to the corresponding benzyne-trapped azo compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410458PMC
May 2021

Reactions of HDDA Benzynes with -Diarylimines (ArCH=NAr').

European J Org Chem 2020 May 13;2020(16):2379-2383. Epub 2020 Feb 13.

Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 USA.

-Benzynes can be utilized to construct heterocyclic motifs using various nucleophilic and cycloaddition trapping reactions. Acridines have been synthesized by capture of -diarylimines with benzynes generated by classical methods (i.e., from -elimination of precursor arene compounds), although in poor yields. We report here that these imines can be trapped by benzynes generated by the hexadehydro-Diels-Alder (HDDA) reaction in an efficient manner to produce 1,4-dihydroacridine products. These dihydroacridines were subsequently aromatized using MnO to provide structurally complex acridines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejoc.201901855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990319PMC
May 2020

Poly(4-ketovalerolactone) from Levulinic acid: Synthesis and Hydrolytic Degradation.

Macromolecules 2020 Jun 10;53(12):4952-4959. Epub 2020 Jun 10.

Department of Chemistry, 207 Pleasant Street, SE, University of Minnesota, Minneapolis, Minnesota 55455, United States.

We report here the synthesis of poly(4-ketovalerolactone) () via ring-opening transesterification polymerization (ROTEP) of the monomer 4-ketovalerolactone (, two steps from levulinic acid). The polymerization of proceeds to high equilibrium monomer conversion (up to 96% in the melt) to give the semicrystalline polyketoester with low dispersity. displays glass transition temperatures of 7 °C and two melting temperatures at 132 and 148 °C. This polyester can be chemically recycled through hydrolytic degradation. Under aqueous neutral or acidic conditions, the dominating pathway for polyester hydrolysis is through backbiting from the chain end. Under basic conditions, mid-chain cleavage, accelerated by the ketone carbonyl group in the backbone, promotes the hydrolysis of nearby backbone ester bonds. The final hydrolysis product is 5-hydroxylevulinic acid, the ring opened hydrolysis product of . was also observed to degrade under the action of a Brønsted acid to a bis-spirocyclic dilactone natural product altaicadispirolactone, which is a dimer of . This constitutes a rare example of a one-step synthesis of a secondary metabolite of non-trivial structure in which a polymer was the starting material and the sole source of matter. Analogous ROTEP of the isomeric 4-membered lactone 4-acetyl-β-propiolactone () was also explored, although this chemistry was not as well-behaved as the to polymerization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.macromol.0c00787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987374PMC
June 2020

Coumarin (5,6-Benzo-2-pyrone) Trapping of an HDDA-Benzyne.

Org Lett 2021 03 2;23(6):2189-2193. Epub 2021 Mar 2.

Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States.

Although the parent 2-pyrone is known to react with simple -benzynes to produce naphthalene derivatives, there appear to be no examples of the successful reaction of coumarin, a benzo-annulated 2-pyrone analogue, with an aryne. We report such a process here using benzynes generated by the hexadehydro-Diels-Alder reaction to produce phenanthrene derivatives (i.e., benzo-annulated naphthalenes). Density functional theory computations were used to help understand the difference in reactivity between 2-pyrone and the slower trapping agent, coumarin. Finally, the reaction of -benzyne itself [from -(trimethylsilyl)phenyl triflate and CsF] with coumarin was shown to be viable, although slow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015840PMC
March 2021

Hexadehydro-Diels-Alder Reaction: Benzyne Generation via Cycloisomerization of Tethered Triynes.

Chem Rev 2021 02 25;121(4):2413-2444. Epub 2021 Jan 25.

Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.

The hexadehydro-Diels-Alder (HDDA) reaction is the thermal cyclization of an alkyne and a 1,3-diyne to generate a benzyne intermediate. This is then rapidly trapped, in situ, by a variety of species to yield highly functionalized benzenoid products. In contrast to nearly all other methods of aryne generation, no other reagents are required to produce an HDDA benzyne. The versatile and customizable nature of the process has attracted much attention due not only to its synthetic potential but also because of the fundamental mechanistic insights the studies often afford. The authors have attempted to provide here a comprehensive compilation of publications appearing by mid-2020 that describe experimental results of HDDA reactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrev.0c00825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008985PMC
February 2021

Characterization of stereoisomeric 5-(2-nitro-1-phenylethyl)furan-2(5H)-ones by computation of H and C NMR chemical shifts and electronic circular dichroism spectra.

Magn Reson Chem 2021 01 15;59(1):43-51. Epub 2020 Jul 15.

Department of Chemistry, Universidade Federal de Viçosa, Viçosa, Brazil.

In the present work, we describe the preparation of two diastereomers from the enantioselective Michael addition of furan-2(5H)-one to (E)-(2-nitrovinyl)benzene catalyzed by a dinuclear Zn-complex. The relative configurations of the diastereomeric products were assigned by comparing nuclear magnetic resonance (NMR) experimental chemical shift data with those computed by density functional theory (DFT) methods. Corrected mean absolute error (CMAE) and CP3 analyses were used to compare the data sets. The absolute configuration of each diastereomer was initially assigned by analysis of electronic circular dichroism (ECD) data, which was consistent with that of the known X-ray crystallographic structure of the product of a related reaction, namely, (R)-5-((R)-1-(4-chlorophenyl)-2-nitroethyl)furan-2(5H)-one.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrc.5073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985851PMC
January 2021

4-Carboalkoxylated Polyvalerolactones from Malic Acid: Tough and Degradable Polyesters.

Macromolecules 2020 Apr 10;53(8):3194-3201. Epub 2020 Apr 10.

Department of Chemistry, 207 Pleasant Street, SE, University of Minnesota, Minneapolis, MN 55455.

Eight 4-carboalkoxyvalerolactones (s), varying in the composition of their alkyl () side chains, were synthesized from malic acid and subjected to ring-opening transesterification polymerization (ROTEP) using diphenyl phosphate [DPP, (PhO)POH] as a catalyst. Each produced a semicrystalline poly(4-carboalkoxyvalerolactone) (), and the nature of the group impacted the thermal transitions of these polyesters. Bulk polymerizations at 70 °C allowed for preparation of high molar mass samples that contained small amounts of branching, as evidenced by H NMR spectroscopy, MALDI spectrometry, size-exclusion chromatography, and eliminative degradation. Tensile testing of these lightly branched, high molar mass samples revealed that these polyesters are tough (tensile toughness values up to 88 ± 33 MJ•m) and have Young's moduli () up to 186 ± 13 MPa. The acid- and base-catalyzed hydrolytic degradation of the s was quantitatively monitored using total organic carbon analysis, and effect of the alkyl chain length on hydrolysis rate was determined. Finally, the methyl ester variant of these malic acid-derived thermoplastics is known to be chemically recyclable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.macromol.0c00212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323767PMC
April 2020

Addendum: A guide to small-molecule structure assignment through computation of (¹H and ¹³C) NMR chemical shifts.

Nat Protoc 2020 07;15(7):2277

Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41596-020-0293-9DOI Listing
July 2020

Reactions of thermally generated benzynes with six-membered -heteroaromatics: pathway and product diversity.

Chem Sci 2019 Oct 14;10(39):9069-9076. Epub 2019 Aug 14.

Department of Chemistry , University of Minnesota , 207 Pleasant St., SE , Minneapolis , MN 55455 , USA . Email:

We report here various pathways by which six-membered -heteroaromatic compounds react with benzynes that are generated by the HDDA reaction. The initially formed 1,3-zwitterionic species (a) can collapse intramolecularly to give novel 1 : 1 adducts of the heterocycle and benzyne; (b) can react with an externally added, electrophilic third-component to give functionalized heterocyclic products; or (c) can react with an external protic nucleophile to produce, following collapse of the ion pair resulting from protonation of the zwitterion, a variety of three-component assemblies. Mechanisms for formation of some of the 1 : 1 adducts are supported by DFT methods. The scope of the protic nucleophilic coupling was also expanded to a two-pot operation by using triflic acid as a protic "non-nucleophile", followed by the addition of a suitably reactive nucleophile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9sc03479jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889833PMC
October 2019

The Aza-hexadehydro-Diels-Alder Reaction.

J Am Chem Soc 2019 12 5;141(50):19575-19580. Epub 2019 Dec 5.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

The generation of pyridynes from diyne nitriles is reported. These cyano-containing precursors are analogues of the triyne substrates typically used for the hexadehydro-Diels-Alder (HDDA) cycloisomerization reactions that produce ring-fused benzynes. Hence, the new processes described represent aza-HDDA reactions. Depending on the location of the nitrile, either 3,4-pyridynes (from 1,3-diynes containing a tethered cyano group) or 2,3-pyridynes (from 1-cyanoethyne derivatives containing a tethered alkyne) are produced. In situ trapping of these reactive intermediates leads to highly substituted and functionalized pyridine derivatives. In several instances, unprecedented pyridyne trapping reactions are seen. Differences in reaction energetics between the aza-HDDA substrates and that of their analogous HDDA (triyne) substrates are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b11243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921493PMC
December 2019

One-Pot, Three-Aryne Cascade Strategy for Naphthalene Formation from 1,3-Diynes and 1,2-Benzdiyne Equivalents.

J Am Chem Soc 2019 06 14;141(25):9813-9818. Epub 2019 Jun 14.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

Here we disclose a cascade strategy for naphthyne formation that capitalizes on the traditional benzyne generation (i.e., from an ortho-silyl aryl triflate) and the thermal hexadehydro-Diels-Alder (HDDA) reaction. In this transformation, three distinct aryne species work in tandem, two of which can be formally considered as a 1,2-benzidyne, and each undergoes a different type of trapping event. Many examples were explored by varying the naphthyne capture chemistry as well as the 1,2-benzdiyne equivalent. This strategy enables rapid construction of various naphthalene products and has potential for the synthesis of extended polycyclic arenes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b04606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933537PMC
June 2019

Divergent Reactivity during the Trapping of Benzynes by Glycidol Analogs: Ring Cleavage via Pinacol-Like Rearrangements vs Oxirane Fragmentations.

Org Lett 2019 04 10;21(8):2615-2619. Epub 2019 Apr 10.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

Hydroxy-containing cyclic ethers react with thermally generated benzynes to produce aryl ethers. Diverse reactivity was observed. Cleavage of the cyclic ether was involved in most of the pathways. The transformations are rationalized via initial formation of oxonium ion-containing 1,3-zwitterions arising from preferential nucleophilic attack on the benzyne by the ether oxygen. Pinacol-like rearrangements, including ring expansion, to yield aldehydes or ketones and oxirane fragmentations to generate aryl enol ethers were main competing events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b00595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742950PMC
April 2019

Benzyne Cascade Reactions via Benzoxetenonium Ions and Their Rearrangements to o-Quinone Methides.

Org Lett 2019 03 4;21(6):1672-1675. Epub 2019 Mar 4.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

A new thermal isomerization of polyynes is described. Benzyne intermediates substituted by a C(RR')OR'' substituent adjacent to one of the benzyne sp-hybridized carbons give rise to products in which the OR' moiety has migrated to the proximal benzyne carbon. This process likely proceeds via sequential formation of multiple reactive intermediates: an initial thermally generated benzyne, a strained benzoxetenonium ion, and an o-quinone methide. As some examples demonstrate, the overall transformation can be quite efficient. The mechanism of this novel reaction is further supported by experiments and DFT calculations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b00215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742951PMC
March 2019

Reactions of Diaziridines with Benzynes Give N-Arylhydrazones.

Org Lett 2018 12 11;20(24):8082-8085. Epub 2018 Dec 11.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

Reactions of thermally generated benzynes with diaziridines are reported. These trapping reactions follow the same pathway as reported earlier by Heine and co-workers with electron-deficient alkynes. The resulting N-arylhydrazones were obtained efficiently in a single step. The preference for the mode of addition of the nucleophilic diaziridine nitrogen atom to the more electrophilic benzyne carbon was consistent with what is predicted on the basis of distortion analysis. The feasibility of converting the hydrazone into a Fisher-indole adduct was demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b03439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465160PMC
December 2018

Sulfonamide-Trapping Reactions of Thermally Generated Benzynes.

Org Lett 2018 11 5;20(22):7145-7148. Epub 2018 Nov 5.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE, Minneapolis , Minnesota 55455 , United States.

Reactions of tethered, tertiary sulfonamides with thermally generated benzynes are reported. Typically, the N-S bonds in the substrates cleave, and saturated heterocycles [tetrahydroquinolines ( n = 2) and indolines ( n = 1)] are formed. The process is accompanied by either sulfonyl transfer or desulfonylation from a zwitterionic intermediate, with the favored pathway being largely dependent upon the size (5- vs 6-membered) of the N-containing ring in the zwitterion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b03085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348468PMC
November 2018

Cu -Mediated Bromoalkynylation and Hydroalkynylation Reactions of Unsymmetrical Benzynes: Complementary Modes of Addition.

Angew Chem Int Ed Engl 2018 12 15;57(50):16564-16568. Epub 2018 Nov 15.

Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN, 55455, USA.

Benzynes formed by heating a suitable triyne (or tetrayne) substrate are shown to react with in situ generated alkynyl copper species. The latter are compatible with the polyyne substrates and two types of chemistries have been achieved: (i) 1-bromo-1-alkynes efficiently undergo net bromoalkynylation of the (unsymmetrical) benzynes and (ii) in situ generated alkynylcopper species give rise to hydroalkynylation products. The regiochemical preferences of these two modes of reaction are complementary to one another with respect to the position of alkynyl substituent in the final products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201811783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386157PMC
December 2018

BF-Promoted, Carbene-like, C-H Insertion Reactions of Benzynes.

J Am Chem Soc 2018 11 8;140(46):15616-15620. Epub 2018 Nov 8.

Department of Chemistry , University of Minnesota , 207 Pleasant Street , SE Minneapolis , Minnesota 55455 , United States.

Boron trifluoride is observed to promote a variety of C-H insertion reactions of benzynes bearing pendant alkyl groups. Computations and various mechanistic studies indicate that BF engages the strained π-bond to confer carbene-like character on the adjacent, noncoordinated benzyne carbon. This represents an unprecedented catalytic role for a non-transition metal such as BF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.8b10206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386166PMC
November 2018

Atypical Mode of [3 + 2]-Cycloaddition: Pseudo-1,3-dipole Behavior in Reactions of Electron-Deficient Thioamides with Benzynes.

Org Lett 2018 09 29;20(18):5550-5553. Epub 2018 Aug 29.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

Thioamides bearing electron-withdrawing groups on the thiocarbonyl carbon atom react with benzynes [generated by the hexadehydro-Diels-Alder cycloisomerization] in an unprecedented fashion. Namely, the dihydrobenzothiazole products are consistent with a pathway involving initial formation of a stabilized ammonium ylide by a rare type of [3 + 2]-cycloaddition reaction. The fate of this species depends upon the nature of the R group(s) attached to the ylide nitrogen atom. The demonstration of new modes of reactivity represents the major advance arising from this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b02133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311210PMC
September 2018

A Traceless Tether Strategy for Achieving Formal Intermolecular Hexadehydro-Diels-Alder Reactions.

Org Lett 2018 09 20;20(17):5502-5505. Epub 2018 Aug 20.

Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.

A synthetic strategy formally equivalent to an intermolecular hexadehydro-Diels-Alder (HDDA) reaction is described. Sulfur-based linkers were designed and constructed by joining terminal alkynes or diynes using alkyne thiolate chemistry. The resulting tetraynes and triynes successfully underwent HDDA cyclization and benzyne trapping. Linker removal by reductive desulfurization was uneventful. The strategy was also found suitable for the tetradehydro-Diels-Alder (TDDA) reaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b02473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354248PMC
September 2018

Fatty-acid derivative acts as a sea lamprey migratory pheromone.

Proc Natl Acad Sci U S A 2018 08 30;115(34):8603-8608. Epub 2018 Jul 30.

Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI 48824;

Olfactory cues provide critical information for spatial orientation of fish, especially in the context of anadromous migrations. Born in freshwater, juveniles of anadromous fish descend to the ocean where they grow into adults before migrating back into freshwater to spawn. The reproductive migrants, therefore, are under selective pressures to locate streams optimal for offspring survival. Many anadromous fish use olfactory cues to orient toward suitable streams. However, no behaviorally active compounds have been identified as migratory cues. Extensive studies have shown that the migratory adult sea lampreys (), a jawless fish, track a pheromone emitted by their stream-dwelling larvae, and, consequently, enter streams with abundant larvae. We fractionated extracts of larval sea lamprey washings with guidance from a bioassay that measures in-stream migratory behaviors of adults and identified four dihydroxylated tetrahydrofuran fatty acids, of which (+)-(2,3,5)-tetrahydro-3-hydroxy-5-[(1)-1-hydroxyhexyl]-2-furanoctanoic acid was shown as a migratory pheromone. The chemical structure was elucidated by spectroscopies and confirmed by chemical synthesis and X-ray crystallography. The four fatty acids were isomer-specific and enantiomer-specific in their olfactory and behavioral activities. A synthetic copy of the identified pheromone was a potent stimulant of the adult olfactory epithelium, and, at 5 × 10 M, replicated the extracts of larval washings in biasing adults into a tributary stream. Our results reveal a pheromone that bridges two distinct life stages and guides orientation over a large space that spans two different habitats. The identified molecule may be useful for control of the sea lamprey.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1803169115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112727PMC
August 2018

Unraveling substituent effects on the glass transition temperatures of biorenewable polyesters.

Nat Commun 2018 07 23;9(1):2880. Epub 2018 Jul 23.

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.

Converting biomass-based feedstocks into polymers not only reduces our reliance on fossil fuels, but also furnishes multiple opportunities to design biorenewable polymers with targeted properties and functionalities. Here we report a series of high glass transition temperature (T up to 184 °C) polyesters derived from sugar-based furan derivatives as well as a joint experimental and theoretical study of substituent effects on their thermal properties. Surprisingly, we find that polymers with moderate steric hindrance exhibit the highest T values. Through a detailed Ramachandran-type analysis of the rotational flexibility of the polymer backbone, we find that additional steric hindrance does not necessarily increase chain stiffness in these polyesters. We attribute this interesting structure-property relationship to a complex interplay between methyl-induced steric strain and the concerted rotations along the polymer backbone. We believe that our findings provide key insight into the relationship between structure and thermal properties across a range of synthetic polymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-05269-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056526PMC
July 2018

The domino hexadehydro-Diels-Alder reaction transforms polyynes to benzynes to naphthynes to anthracynes to tetracynes (and beyond?).

Nat Chem 2018 08 20;10(8):838-844. Epub 2018 Jul 20.

Department of Chemistry, University of Minnesota, Minneapolis, MN, USA.

Polyacenes are organic compounds that have multiple, fused, aromatic rings. These highly conjugated molecules often have interesting photonic and/or electronic properties that afford them the potential for application in a host of organoelectronic devices such as sensors, light-emitting diodes, photovoltaic devices and field-effect transistors. Here, we show the development and use of the domino hexadehydro-Diels-Alder reaction to synthesize structurally diverse polyacenes from acyclic polyyne precursors. The key event in these transformations is the successive reaction of multiple 1,3-butadiyne units with a series of in-situ-generated, diynophilic arynes. The polyyne substrates were designed to allow for rapid engagement of each progressively larger aryne following the initiating (and ratelimiting) production of the first reactive intermediate-the benzyne. We show that aryne-trapping reactions are broad in scope and that these cascade or domino processes can be quite efficient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41557-018-0075-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284823PMC
August 2018

Isomerizations of Propargyl 3-Acylpropiolates via Reactive Allenes.

Org Lett 2018 08 12;20(15):4425-4429. Epub 2018 Jul 12.

Department of Chemistry , University of Minnesota , 207 Pleasant St. SE , Minneapolis , Minnesota 55455 , United States.

Thermal isomerizations of various propargyl 3-acylpropiolates are described. Many result in the formation of 3-acylbutenolides. These reactions appear to proceed through intermediate 2,3-dehydropyrans (strained cyclic allenes), which then isomerize in a previously unobserved fashion. Competitive processes that provide additional mechanistic insights are also described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b01705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400065PMC
August 2018

Benzocyclobutadienes: An Unusual Mode of Access Reveals Unusual Modes of Reactivity.

Angew Chem Int Ed Engl 2018 07 4;57(31):9901-9905. Epub 2018 Jul 4.

Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, Minnesota, 55455, USA.

The reaction of an aryne with an alkyne to generate a benzocyclobutadiene (BCB) intermediate is rare. We report here examples of this reaction, revealed by Diels-Alder trapping of the BCB by either pendant or external electron-deficient alkynes. Mechanistic delineation of the reaction course is supported by DFT calculations. A three-component process joining the benzyne first with an electron-rich and then with an electron-poor alkyne was uncovered. Reactions in which the BCB functions in a rarely observed role as a 4π diene component in Diels-Alder reactions are reported. The results also shed new light on aspects of the hexadehydro-Diels-Alder reaction used to generate the benzynes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201803872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296485PMC
July 2018

Engineering the production of dipicolinic acid in E. coli.

Metab Eng 2018 07 21;48:208-217. Epub 2018 May 21.

Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Ave. SE, Minneapolis, MN 55455, USA.

Dicarboxylic acids, such as the phthalic acids and their derivatives, are monomeric components in several important polyesters and polyamides. In most cases, these compounds are derived from fossil fuels and are not easily biodegradable. Dipicolinic acid (DPA) is a biologically derived aromatic di-acid that has a similar structure to isophthalic acid. Furthermore, DPA has been shown to give rise to polyesters, is readily biodegradable, and is non-toxic. DPA is naturally produced by Bacillus and Clostridium species during sporulation and can comprise up to 15% of the dry weight of bacterial spores. In this paper we demonstrate the first heterologous production of DPA and identify the genes appropriate for gram-scale production in the industrial workhorse organism, E. coli. Initially, several combinations of genes from the lysine pathway, including lysC, asd, dapA, and dapB, were overexpressed to determine which genes are necessary for recombinant production in E. coli. The in vitro activity of dipicolinate synthase was then compared between Bacillus subtilis and Clostridium perfringens. Next, in order to improve DPA production from glucose, an optimized strain was created that lacked several genes (lysA, tdh, and metA), resulting in 5.21 g/L DPA when 5 g/L of aspartate was supplied. Then, several aspartate kinases and dipicolinate synthases were screened for optimal activity in E. coli. The optimal genes were combined with the overexpression of phosphoenolpyruvate carboxylase to develop a full biosynthetic pathway capable of producing a titer of 4.7 g/L DPA directly from glucose. In summary, we have performed a detailed biochemical study of the key pathway enzyme dipicolinate synthase and achieved scalable heterogeneous production of DPA in the workhorse organism E. coli.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymben.2018.05.009DOI Listing
July 2018
-->