Intramolecular Olefin Insertion Research Articles

Origin of Enantio- and Chemoselectivity in the Synthesis of Spirocycles via Palladium/Xu-Phos-Catalyzed Cascade Heck/Remote C(sp2)-H Alkylation: A Computational Mechanistic Study.

Density functional theory (DFT) calculations were performed to study the mechanism and factors affecting the enantio-, regio-, and chemoselectivities in the palladium/Xu-Phos-catalyzed cascade Heck/remote C(sp2)-H alkylation reaction. The active catalyst is found to be able to sustain coordination with P and S atoms and can adapt its coordination mode to accommodate the significant steric hindrance between the ligand and substrate, unlike previous findings that showed coordination with P and O atoms. The reaction is established to occur in sequence through the oxidative addition of the aryl iodide to Pd(0), intramolecular alkene insertion, C(sp2)-H bond activation, and C(sp2)-C(sp3) bond reductive elimination. The C(sp2)-C(sp3) bond reductive elimination is identified as the rate-determining step, and the intramolecular alkene insertion as the enantioselectivity-determining step. The high enantioselectivity originates from the stronger electronic interaction between the catalyst and substrate; the exclusive 5-exo-regioselectivity is due to the stronger nucleophilicity of the terminal alkene carbon atom, and the chemoselectivity of C-H activation over carboiodination is driven by thermodynamics.

Computational Study on the Co-Mediated Intramolecular Pauson-Khand Reaction of Fluorinated and Chiral N-Tethered 1,7-Enynes.

The Co2(CO)8-mediated intramolecular Pauson–Khand reaction is an elegant approach to obtain cyclopentenone derivatives containing asymmetric centers. In this work, we employed density functional theory calculations at the M11/6-311+G(d,p) level of theory to investigate the mechanism and reactivity for the Pauson–Khand reaction of fluorinated and asymmetric N-tethered 1,7-enynes. The rate-determining step was found to be the intramolecular alkene insertion into the carbon–cobalt bond. The stereoselectivity of the alkene insertion step was rationalized by the different transition states showing the coordination of the alkene through the Re- and Si-face. The effects of different fluorine groups and steric effects on both the alkenyl and alkynyl moieties were also theoretically investigated.

Palladium(II)‐Catalyzed Direct Access to Indeno[1,2‐c]isochromen‐5(11H)‐Ones via Intramolecular Oxypalladation‐Initiated Cascade Process

AbstractA palladium(II)‐catalyzed cascade approach was established for the synthesis of indeno[1,2‐c]isochromen‐5(11H)‐ones starting from 2‐alkynyl tert‐butyl benzoates bearing a pendant α,β‐unsaturated carbonyl moiety in high yields (up to 99%) under mild conditions. This strategy offered high atom and step economy by delivering isobutene as the only side product, and by generating two new bonds and two rings in a single synthetic operation. The mechanism of the cascade process was visualized comprising sequential intramolecular oxypalladation (6‐endo‐dig), intramolecular olefin insertion, and protonation steps.magnified image

Palladium-Catalyzed Regioselective Syn-Chloropalladation-Olefin Insertion-Oxidative Chlorination Cascade: Synthesis of Dichlorinated Tetrahydroquinolines.

A palladium catalyzed cascade process involving syn-chloropalladation, intramolecular olefin insertion, and oxidative C-Cl bond formation reactions was demonstrated for the synthesis of dichlorinated tetrahydroquinolines in high yields (up to 93%). The N-propargyl arylamines having a tethered α,β-unsaturated carbonyl moiety underwent a regioselective syn-chloropalladation followed by a Heck-type reaction to deliver the tetrahydroquinoline scaffold. The rare insertion of the second chlorine atom was rationalized comprising a PdII/IV catalytic cycle and oxidative cleavage of the C-PdII bond.

Key Mechanistic Features in Palladium-Catalyzed Methylcyclopropanation of Norbornenes With Vinyl Bromides: Insights From DFT Calculations.

DFT calculations were performed to elucidate mechanistic details of an unusual palladium-catalyzed methylcyclopropanation from [2 + 1] cycloadditions of (Z)-2-bromovinylbenzene and endo-N-(p-tolyl)-norbornenesuccinimide. The reaction proceeds via oxidative addition (OA), intermolecular alkene insertion, deprotonation/protonation, intramolecular alkene insertion, β-H elimination and reductive elimination (RE). Protonation is the rate-limiting step and requires an overall barrier of 28.5 kcal/mol. The sources of two protons for protonation and exchange have also been clarified and the calculations agree with experimental observations.

Metal-free alkene carbooxygenation following tandem intramolecular alkoxylation/Claisen rearrangement: stereocontrolled access to bridged [4.2.1] lactones.

Alkene carbooxygenation has attracted considerable attention over the past few decades as this approach provides an efficient access to various oxygen-containing molecules, especially the valuable O-heterocycles. However, examples of catalytic alkene carbooxygenation via a direct C-O cleavage are quite scarce, and the C-O cleavage in these cases is invariably initiated by transition metal-catalyzed oxidative addition. We report here a novel Brønsted acid-catalyzed intramolecular alkoxylation-initiated tandem sequence, which represents the first metal-free intramolecular alkoxylation/Claisen rearrangement. Significantly, an unprecedented Brønsted acid-catalyzed intramolecular alkene insertion into the C-O bond via a carbocation pathway was discovered. This method allows the stereocontrolled synthesis of valuable indole-fused bridged [4.2.1] lactones, providing ready access to biologically relevant scaffolds in a single synthetic step from an acyclic precursor. Moreover, such an asymmetric cascade cyclization has also been realized by employing a traceless chiral directing group. Control experiments favor the feasibility of a carbocation pathway for the process. In addition, biological tests showed that some of these newly synthesized indole-fused lactones exhibited their bioactivity as antitumor agents against different breast cancer cells, melanoma cells, and esophageal cancer cells.

Theoretical insight into the mechanisms of palladium-catalyzed intramolecular insertion of alkenes into the carbon-nitrogen bond of β-lactam

By employing density functional theory (DFT), we investigate the mechanisms of Pd-catalyzed intramolecular alkene insertion with β-lactam. The catalytic cycle involves oxidative addition, alkene insertion, and reductive elimination. In reaction A, the rate-determining step is the alkene insertion. Compared with reaction A, the higher barriers for reactions B and C could be attributed to the weaker electron-donating ability of ligands and the strong steric repulsion between the ligands and the substrate, respectively. When the methyl group is substituted by the electron-withdrawing phenyl group (reaction D), the alkene insertion becomes more difficult due to the electronic effect, which is consistent with the observation that the yield is low in this reaction.

Synthesis of 2-Benzazepines from Benzylamines and MBH Adducts Under Rhodium(III) Catalysis via C(sp2)–H Functionalization

The rhodium(III)-catalyzed cross-coupling reaction between commercially available benzylamines and Morita–Baylis–Hillman (MBH) adducts is described. This protocol provides a facile access to various 2-benzazepine derivatives via the C(sp2)–H activation of N-allylated benzylamines and subsequent intramolecular olefin insertion followed by N-allylation reaction. A range of substrates has been used, and a high level of chemoselectivity as well as functional group tolerance was observed. To gain mechanistic insight of this transformation, DFT calculations were also performed.

Iridium-Catalyzed Formal [4 + 1] Cycloaddition of Biphenylenes with Alkenes Initiated by C-C Bond Cleavage for the Synthesis of 9,9-Disubstituted Fluorenes.

An Ir-catalyzed intermolecular reaction of biphenylenes as a C4 unit with various alkenes as a C1 unit gave 9,9-disubstituted fluorenes in moderate to high yields. Preliminary mechanistic studies revealed that this formal [4 + 1] cycloaddition probably proceeds via C-C bond cleavage, alkene insertion, β-hydrogen elimination, intramolecular alkene insertion, and then reductive elimination. An example of enantioselective reaction was also disclosed.

ChemInform Abstract: Palladium‐Catalyzed Intramolecular Insertion of Alkenes into the Carbon—Nitrogen Bond of β‐Lactams.

AbstractThe title reaction proceeds via cleavage of the C—N bond of β‐lactams (I) and (III) by Pd(0) followed by intramolecular alkene insertion.

What Controls Stereoselectivity and Reactivity in the Synthesis of a trans-Decalin with a Quaternary Chiral Center via the Intramolecular Pauson–Khand Reaction: A Theoretical Study

The Co2(CO)8-mediated intramolecular Pauson–Khand reaction is an efficient approach to the trans-decalin subunit with a defined C1 quaternary chiral center. The newly developed density functional theory method M11-L was employed to study the mechanism, reactivity, and stereoselectivity for this reaction. The rate- and stereoselectivity-determining step is the intramolecular alkene insertion into the carbon–cobalt bond. Insertion of the alkene by the re- and si-face was studied to explain the stereoselectivity. The effects of varying the substituent on the acetylene and the C3 chirality were investigated experimentally and theoretically.

ChemInform Abstract: Atom‐ and Step‐Economical Pathway to Chiral Benzobicyclo[2.2.2]octenones Through Carbon—Carbon Bond Cleavage.

AbstractThe asymmetric intramolecular alkene insertion reaction of 3‐(2‐styryl)cyclobutanones is efficiently catalyzed by Ni(cod)2 in the presence of PAM.

Palladium-Catalyzed Cycloisomerizations of (Z)-1-Iodo-1,6-dienes: Iodine Atom Transfer and Mechanistic Insight to Alkyl Iodide Reductive Elimination

A palladium-catalyzed iodine atom transfer cycloisomerization of (Z)-1-iodo-1,6-diene has been developed, which provides a facile method to construct six-memebered heterocycles bearing an alkyl iodide group. The ligand screening shows that both the type and the quantity of ligand impose significant influences on this transformation, and the combination of 30 mol % 1,1'-bis(diphenylphosphino)ferrocene (DPPF) and 10 mol % Pd(OAc)(2) is the optimal choice. The catalytic cycle, consisting of oxidative addition of Pd(0) to vinyl iodide, intramolecular alkene insertion, and alkyl iodide reductive elimination, has been proposed and eventually supported by convincing evidence from a series of control experiments. More importantly, these control experiments disclose some features of the event of alkyl iodide reductive elimination: (1) this reductive elimination is proved to be a stereospecific process; and (2) both alkyl iodide oxidative addition and reductive elimination are not effected by a TEMPO additive. Besides its ability to undergo oxidative addition, the catalyst (palladium + DPPF) could also promote a radical transfer process. The findings described in this paper will be helpful for further development of the metal-catalyzed formation of a carbon-halide bond.

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

Stereoselective Synthesis of Isoxazolidines through Pd‐Catalyzed Carboetherification of <i>N</i>‐Butenylhydroxylamines

Synthesis of Dimethyl Gloiosiphone A by Way of Palladium-Catalyzed Domino Cyclization

The synthesis of a spiro[4.4]nonane skeleton by the palladium-catalyzed domino cyclization of a linear 7-methylene-2,10-undecadienyl acetate is described. The pi-allylpalladium intermediate underwent intramolecular alkene insertion with high intraannular diastereoselectivity, followed by intramolecular Heck-type cyclization, leading to a spiro[4.4]nonane system. Oxidation of the allylic ether moiety and transformation of the vinyl group to an exo-methylene unit provided 3, which is the known synthetic intermediate of dimethyl gloiosiphone A (2).

Palladium-catalyzed intra-molecular olefin insertion reaction of α-alkenyl-α-acyloxytrialkylsilane. Synthesis of optically active carbocycle

Pd-catalyzed intra-molecular olefin insertion/carbonylation reaction of optically active α-alkenyl-α-acyloxysilanes is described. The reactions proceeded in a stereoselective manner to give five- and six-membered optically active carbocycles having ( E)-vinylsilane in their side chains. Under CO condition, optically active carbocycles containing one-carbon homologated side chain were produced by Pd-catalyzed tandem olefin insertion–carbonylation reaction.

Nickel-catalysed intramolecular alkene insertion into cyclobutanones

A nickel(0) catalyst converted 3-styrylcyclobutanones into benzobicyclo[2.2.2]octenones by an intramolecular insertion of the vinyl moiety into the cyclobutanone skeleton.

Palladium-catalyzed synthesis of N-aryl pyrrolidines from gamma-(N-Arylamino) alkenes: evidence for chemoselective alkene insertion into Pd--N bonds.

The formation of a CC and a CN 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 PdN bond of intermediate [Pd(Ar)(amido)] complexes. dba=dibenzylideneacetone, dppb=1,3-bis(diphenylphosphanyl)butane. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460060_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Stereoselective Synthesis of Tetrahydrofurans via the Palladium‐Catalyzed Reaction of Aryl Bromides with γ‐Hydroxy Alkenes: Evidence for an Unusual Intramolecular Olefin Insertion into a Pd(Ar)(OR) Intermediate.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation and ligand substitution reactions of Tp MsRu(COD)H including intramolecular ligand metalation

Reaction of [RuH(COD)(NH 2N(CH 3) 2) 3]BPh 4 (COD=1,5-cyclooctadiene) with Tp MsTl (Tp Ms=hydrotris(3-mesitylpyrazolyl)borate) yielded Tp MsRu(COD)H ( 1). Treatment of 1 with CO afforded acyl complex Tp MsRu(CO) 2C(O)C 8H 13 ( 2) via intramolecular olefin insertion followed by CO addition and insertion. In contrast, reaction of 1 with acetonitrile was accompanied by C–H activation of a ligand methyl group and H 2 elimination, ultimately producing Tp Ms@Ru(NCCH 3) 2 ( 3) as the final product. The molecular structures of complexes 1– 3 have been determined by single crystal X-ray diffraction methods.