Synthesis of 3,4-disubstituted 2H-benzopyrans through C-C bond formation via electrophilic cyclization.
ABSTRACT: The electrophilic cyclization of substituted propargylic aryl ethers by I2, ICl, and PhSeBr produces 3,4-disubstituted 2H-benzopyrans in excellent yields. This methodology results in vinylic halides or selenides under mild reaction conditions and tolerates a variety of functional groups, including methoxy, alcohol, aldehyde, and nitro groups.
Project description:2,3-Disubstituted benzo[b]selenophenes have been prepared by the electrophilic cyclization of various 1-(1-alkynyl)-2-(methylseleno)arenes by Br2, NBS, I2, ICl, PhSeCl, PhSeBr, and Hg(OAc)2. This method tolerates a wide variety of functional groups, including alcohol, ester, nitrile, nitro, and silyl groups, and proceeds under exceptionally mild reaction conditions.
Project description:[reactions: see text] A wide variety of substituted naphthalenes are readily prepared regioselectively under mild reaction conditions by the 6-endo-dig electrophilic cyclization of appropriate arene-containing propargylic alcohols by ICl, I2, Br2, NBS, and PhSeBr. 3-Iodo-2-naphthols have also been prepared in excellent yields by the cyclization of analogous 1-aryl-3-alkyn-2-ones. This methodology readily accommodates various functional groups and has been successfully extended to the synthesis of substituted carbazoles and dibenzothiophenes.
Project description:Highly substituted 1H-isochromenes, isobenzofurans, and pyranopyridines can be prepared by allowing o-(1-alkynyl)arenecarboxaldehydes and ketones to react with I2, ICl, NIS, Br2, NBS, p-O2NC6H4SCl, or PhSeBr and various alcohols or carbon-based nucleophiles at room temperature. Naphthyl ketones and iodides are also readily prepared by the reaction of 2-(1-alkynyl)arenecarboxaldehydes with I2 and simple olefins or alkynes.
Project description:The original goal of this research was to study stereochemistry of selenium dihalides addition to cycloalkenes and properties of obtained products. Remarkable alkene-to-alkene and alkene-to-alkyne transfer reactions of selenium dibromide and PhSeBr were discovered during this research. The adducts of selenium dibromide with alkenes or cycloalkenes easily exchange SeBr2 with other unsaturated compounds, including acetylenes, at room temperature, in acetonitrile. Similar alkene-to-alkene and alkene-to-alkyne transfer reactions of the PhSeBr adducts with alkenes or cycloalkenes take place. The supposed reaction pathway includes the selenium group transfer from seleniranium species to alkenes or alkynes. It was found that the efficient SeBr2 and PhSeBr transfer reagents are Se(CH2CH2Br)2 and PhSeCH2CH2Br, which liberate ethylene, leading to a shift in equilibrium. The regioselective and stereoselective synthesis of bis(E-2-bromovinyl) selenides and unsymmetrical E-2-bromovinyl selenides was developed based on the SeBr2 and PhSeBr transfer reactions which proceeded with higher selectivity compared to analogous addition reactions of SeBr2 and PhSeBr to alkynes under the same conditions.
Project description:A wide variety of substituted quinolines are readily synthesized under mild reaction conditions by the 6-endo-dig electrophilic cyclization of N-(2-alkynyl)anilines by ICl, I(2), Br(2), PhSeBr and p-O(2)NC(6)H(4)SCl. The reaction affords 3-halogen-, selenium- and sulfur-containing quinolines in moderate to good yields in the presence of various functional groups. Analogous quinolines bearing a hydrogen in the 3-position have been synthesized by the Hg(OTf)(2)-catalyzed ring closure of these same alkynylanilines.
Project description:Investigation of photochromic and acidochromic behaviors of a set of pyridyl- and pyrimidylethynylated mono- and bis-benzopyrans reveals an intriguing influence of the <i>N</i>-heteroaryl ring on spectrokinetic properties of the photogenerated <i>o</i>-quinonoid colored reactive intermediates. While the absorption maxima of the pyridylethynylated bis-benzopyran and its photogenerated <i>o</i>-quinonoid colored species undergo bathochromic shifts by ca. 40 and 22 nm, respectively, in the presence of an acid (e.g., trifluoroacetic acid (TFA)), the same remain unaffected for the analogous pyrimidylethynylated bis-benzopyran and its photogenerated <i>o</i>-quinonoid colored species under similar conditions. Modification of the photochromic behavior of these benzopyrans and, hence, spectrokinetic properties of their photogenerated <i>o</i>-quinonoid species in the presence of H<sup>+</sup> is a consequence of relative proton affinities of <i>N</i>-heteroaryl rings, i.e., pyridyl/pyrimidyl, and the resonance effects relayed through the ethynyl spacers in a push-pull π-delocalized-type skeleton; the mesomeric effects operate in a contrasting manner depending on the <i>N</i>-heteroaryl ring in the absence and in the presence of an acid. These molecular systems offer a unique opportunity to modulate both photochromic and acidochromic properties of benzopyrans and their photogenerated colored <i>o</i>-quinonoid intermediates by leveraging <i>N</i>-heteroaromatic rings.
Project description:[reaction: see text] 2,3-Disubstituted benzo[b]furans are readily prepared under very mild reaction conditions by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization with I2, PhSeCl, or p-O2NC6H4SCl. Aryl- and vinylic-substituted alkynes undergo electrophilic cyclization in excellent yields. Biologically important furopyridines can be prepared by this approach in high yields.
Project description:The first transition metal catalyzed asymmetric carboalkoxylation reaction of propargyl esters is described. The (R)-MeO-DTBM-BIPHEP(AuCl)(2)-catalyzed reactions allow for the construction of benzopyrans containing quaternary stereocenters with excellent enantioselectivity. Experimental evidence supports a mechanism proceeding via the generation of a stabilized carbocation from an allylic oxonium intermediate and subsequent trapping by a chiral allylgold(I) spieces.
Project description:Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect <i>Leishmania</i> growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, <i>Leishmania tarentolae</i>. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the <i>Leishmania tarentolae</i> and thus provide impetus for the development and testing of a more extensive library.
Project description:The palladium-catalyzed 1,1-alkynylbromination of terminal alkenes with a silyl-protected alkynyl bromide is reported. The method tolerates a diverse range of alkenes including vinylarenes, acrylates, and even electronically unbiased alkene derivatives to afford propargylic bromides regioselectively. Mechanistic studies and DFT calculations indicate that the 1,1-alkynylbromination reaction proceeds <i>via</i> the migration of the Pd center followed by the formation of a π-allenyl Pd intermediate, leading to the stereoselective reductive elimination of the C(sp<sup>3</sup>)-Br bond at the propargylic positon.