Titanocene-catalyzed carbosilylation of alkenes and dienes using alkyl halides and chlorosilanes

A new method for regioselective carbosilylation of alkenes and dienes has been developed by the use of a titanocene catalyst. This reaction proceeds efficiently at 0 degrees C in THF in the presence of Grignard reagents by the combined use of alkyl halides (R'-X, X = Br or Cl) and chlorotrialkylsilanes (R3'Si-Cl) as the alkylating and silylating reagents, respectively. Terminal alkenes having aryl or silyl substituents (YRC=CH2, Y = Ar or Me3Si, R = H or Me) afford addition products YRC-(SiR'3)-CH2R' in good yields, whereas 1-octene and internal alkenes were sluggish. When 2,3-disubstituted 1,3-butadienes were used instead of alkenes, alkyl and silyl units are introduced at the 1- and 4-positions giving rise to allylsilanes in high yields under similar conditions. The present reaction involves (i) addition of alkyl radicals toward alkenes or dienes, and (ii) electrophilic trapping of benzyl- or allylmagnesium halides with chlorosilanes. The titanocene catalyst plays important roles in generation of these active species, i.e., alkyl radicals and benzyl- or allylmagnesium halides.     

Addition of carboxyalkyl radicals to alkenes through a catalytic process,using a Mn(II)/Co(II)/O2 redox system

A novel strategy for production of mono- and dicarboxylic acids by the addition of carboxyalkyl radicals to alkenes and dienes, respectively, was successfully developed through a catalytic process with use of Mn(II)/Co(II)/O(2) system. Thus, a variety of carboxylic acids were prepared by the reaction of alkenes and dienes with acid anhydrides in the presence of a very small amount of Mn(OAc)(2) (0.5 mol %) and Co(OAc)(2) (0.1 mol %) under dilute dioxygen.     

3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.     

Highly enantioselective Diels-Alder reactions of Danishefsky type dienes with electron-deficient alkenes catalyzed by Yb(III)-BINAMIDE complexes

1-Methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky's diene) is recognized as a synthetically useful diene due to its high reactivity in the Diels-Alder reaction with electron-deficient alkenes to give oxygen-functionalyzed cyclohexenes and substituted cyclohexenones, which are important building blocks for the total synthesis of natural products. However, the development of catalytic enantioselective versions of Diels-Alder reactions using Danishefsky type dienes with electron-deficient alkenes has been difficult because of the instability of the dienes under Lewis acidic conditions. Only highly reactive CO and CN double bonds are employed in a hetero-Diels-Alder reaction which proceeds under catalysis of chiral Lewis acids. We have developed a new chiral ligand, BINAMIDE, which is easily prepared from 1,1'-binaphtyl-2,2'-diamine by acylation. The highly diastereo- and enantioselective Diels-Alder reaction of Danishefsky type dienes with electron-deficient alkenes in the presence of an Yb(III)-BINAMIDE complex has been developed. The reaction proceeded in an exoselective mode and gave chiral highly functionalized cyclohexene derivatives in good yields.     

Direct entry to peptidyl ketones via SmI2-mediated C-C bond formation with readily accessible N-peptidyl oxazolidinones

In this work, a new method for the preparation of peptidyl ketones is presented employing a SmI(2)/H(2)O-mediated coupling of N-peptidyl oxazolidinones with electron-deficient alkenes. The requisite peptide imides were easily prepared by solution-phase peptide synthesis starting from an N-acyl oxazolidinone derivative of an amino acid. Importantly, they could be used directly in the C-C bond-forming step without the need for further functionalization. Coupling of these peptide derivatives with a second peptide possessing an N-terminal acryloyl group leads to ketomethylene isosteres of glycine-containing peptides. This method represents an alternative means for ligating two small peptides through a C-C bond-forming step.     

Regioselectivity and diasteroselectivity in Pt(II)-mediated "green" catalytic epoxidation of terminal alkenes with hydrogen peroxide: mechanistic insight into a peculiar substrate selectivity

Recently developed electron-poor Pt(II) catalyst 1 with the "green" oxidant 35% hydrogen peroxide displays high activity and complete substrate selectivity in the epoxidation of terminal alkenes because of stringent steric and electronic requirements. In the presence of isolated dienes bearing terminal and internal double bonds, epoxidation is completely regioselective toward the production of terminal epoxides. Insight into the mechanism is gained by means of a reaction progress kinetic analysis approach that underlines the peculiar role of 1 in activating both the alkene and H2O2 in the rate-determining step providing a rare example of nucleophilic oxidation of alkenes by H2O2.     

Electrochemical Synthesis of (Aza)indolines via Dehydrogenative [3+2] Annulation: Application to Total Synthesis of (±)‐Hinckdentine A

An electrochemical synthesis of functionalized (aza)indolines through dehydrogenative [3+2] annulation of arylamines with tethered alkenes has been developed. Previous reported syntheses through similar inter‐ and intramolecular annulation reactions required noble‐metal catalysts and are mostly limited to terminal alkenes or 1,3‐dienes. The electrosynthesis employs the easily available and inexpensive ferrocene as the molecular catalyst and is compatible with di‐, tri‐ and even tetrasubstituted alkenes to construct indolines as well as the more challenging azaindolines. Employing the newly developed electrosynthesis as a key step, the total synthesis of marine alkaloid (±)‐hinckdentine A has been achieved in 12 steps (longest linear sequence) from commercially available materials.     

(Triphenyl phosphite)gold(I)-catalyzed intermolecular hydroamination of alkenes and 1,3-dienes

Intermolecular addition of different sulfonamides to alkenes and conjugated dienes can be carried out using a low loading of (triphenyl phosphite)gold(I) chloride and silver triflate as a catalytic mixture. The reaction can be performed under conventional thermal or microwave conditions and at rt in the case of dienes. Terminal alkenes undergo regioselective hydroamination at the internal carbon atom and dienes at the less substituted double bond.     

Theoretical study on the enantioselective α-amination reaction of 1,3-dicarbonyl compounds catalyzed by a bifunctional-urea

The direct catalytic enantioselective α-amination reaction of carbonyl compounds, a powerful approach to asymmetric carbon–nitrogen bond-forming, has been extensively studied, however, our understanding of the mechanism is far from complete. A theoretical study is presented for the α-amination reaction of 2-acetylcyclopentanone with azodicarboxylate catalyzed by a urea-based chiral bifunctional organocatalyst. By performing density functional theory (DFT) calculations, we have identified a detailed mechanism of the reaction and the roles of the amino group and urea in the catalyst. The structures of the catalyst, substrates, intermediates, and transition states involved in the reaction have been located along four possible reaction channels. The rate-determining step is the C–N bond-forming step. The calculations show that the catalyst promotes the reaction by deprotonating 2-acetylcyclopentanone and forming hydrogen bonds with the substrates. The origin of enantioselectivity of the reaction is also discussed.     

Ruthenium carbenes as catalysts in stereoselective ene–yne metathesis/Diels–Alder and ene–yne metathesis/Diels–Alder/cross coupling multicomponent reactions

An ene–yne cross metathesis of silyl substituted alkynes and alkenes followed by a Diels–Alder reaction of the metathesis product 2-silyl-1,3-dienes has been developed. The dienes thus prepared in situ were shown to participate in highly diastereoselective Diels–Alder reactions. In one case the silicon substituted Diels–Alder cycloadduct was subsequently used without isolation and purification in a Hiyama cross coupling reaction. The cross coupling reactions enable these silicon dienes to be used as synthons for a variety of other dienes.     

(Z)-tamoxifen and tetrasubstituted alkenes and dienes via a regio- and stereospecific three-component magnesium carbometalation palladium(0) cross-coupling strategy

[reaction: see text] The synthesis of various tetrasubstituted alkenes and dienes in a regio- and stereocontrolled manner is described. This three-component coupling strategy involves the addition of Grignard reagents to propargyl alcohols followed by palladium(0)-mediated cross-coupling with aryl or vinyl halides. This protocol has been applied to the synthesis of (Z)-Tamoxifen and related mimics.     

Acetylene as a Dicarbene Equivalent for Gold(I) Catalysis: Total Synthesis of Waitziacuminone in One Step

The gold(I)‐catalyzed reaction of acetylene gas with alkenes leads to (Z,Z)‐1,4‐disubstituted 1,3‐butadienes and biscyclopropanes depending on the donor ligand on gold(I). Acetylene was generated in situ from calcium carbide and water in a user‐friendly procedure. Reaction of acetylene with 1,5‐dienes gives rise stereoselectively to tricyclo[5.1.0.0^2,4]octanes. This novel double cyclopropanation has been applied to the one step total synthesis of the natural product waitziacuminone from acetylene and geranyl acetone.     

Palladium-catalyzed carboiodination of alkenes: carbon-carbon bond formation with retention of reactive functionality

We report a palladium-catalyzed carbon-carbon bond-forming reaction between aryl iodides and alkenes. In contrast to traditional cross-coupling reactions, two new bonds are formed, and all of the atoms in the starting materials are incorporated into the product. The use of a palladium catalyst with bulky phosphine ligands is found to be crucial for reactivity.     

Gold(I)-catalyzed intermolecular hydroarylation of alkenes with indoles under thermal and microwave-assisted conditions

An efficient method for intermolecular hydroarylation of aryl and aliphatic alkenes with indoles using a combination of [(PR(3))AuCl]/AgOTf as catalyst under thermal and microwave-assisted conditions has been developed. The gold(I)-catalyzed reactions of indoles with aryl alkenes were achieved in toluene at 85 degrees C over a reaction time of 1-3 h with 2 mol% of [(PR(3))AuCl]/AgOTf as catalyst. This method works for a variety of styrenes bearing electron-deficient, electron-rich, and sterically bulky substituents to give the corresponding products in good to high yields (60-95%). Under microwave irradiation, coupling of unactivated aliphatic alkenes with indoles gave the corresponding adducts in up to 90% yield. Selective hydroarylation of terminal C=C bond of conjugated dienes with indoles gave good product yields (62-81%). On the basis of deuterium-labeling experiments, a reaction mechanism involving nucleophilic attack of Au(I)-coordinated alkenes by indoles is proposed.     

Copper-catalyzed oxidative trifluoromethylation of terminal alkenes using nucleophilic CF3SiMe3: efficient C(sp3)-CF3 bond formation

An efficient C(sp(3))-CF(3) bond-forming reaction via Cu-catalyzed oxidative trifluoromethylation of terminal alkenes has been developed, which proceeds under mild conditions using readily available, less expensive CF(3)SiMe(3) as the source of the CF(3) group. This method allows access to a variety of trifluoromethylated allylic compounds.     

Catalytic cyclopropanation of alkenes via (2-furyl)carbene complexes from 1-benzoyl-cis-1-buten-3-yne with transition metal compounds

The reaction of alkenes with conjugated ene-yne-ketones, such as 1-benzoyl-2-ethynylcycloalkenes, with a catalytic amount of Cr(CO)(5)(THF) gave 5-phenyl-2-furylcyclopropane derivatives in good yields. The key intermediate of this cyclopropanation is a (2-furyl)carbene complex generated by a nucleophilic attack of carbonyl oxygen to an internal alkyne carbon in pi-alkyne complex or sigma-vinyl cationic complex. A wide range of late transition metal compounds, such as [RuCl(2)(CO)(3)](2), [RhCl(cod)](2), [Rh(OAc)(2)](2), PdCl(2), and PtCl(2), also catalyzes the cyclopropanation of alkenes with ene-yne-ketones effectively. When the reactions were carried out with dienes as a carbene acceptor, the more substituted or more electron-rich alkene moiety was selectively cyclopropanated with the (2-furyl)carbenoid intermediate.     

Inorganic and organometallic chemistry of PtIII complexes having a delocalized PtIII—PtIII bond

Amidate-bridged dinuclear Pt^III complexes having a Pt^III—Pt^III bond react with ketones and alkenes. In the reaction with alkenes in water, 1,2-diols are obtained. In the reactions with conjugated dienes, stereospecific 1,4-diols are formed selectively. A kinetic study revealed that at each intermediate step of the reaction with alkenes the electronic state of the Pt—Pt bond changes between Pt^III—Pt^III and Pt^II—Pt^IV and stabilizes the reaction intermediates.     

Radical Carbofluorination of Alkenes with Arylhydrazines and Selectfluor: Additives,Mechanistic Pathways,and Polar Effects

Radical carbofluorination reactions starting from arylhydrazines and nonactivated alkenes, in which the C−F bond is formed through the use of Selectfluor, can be improved through the addition of anisole. Because direct trapping products could be detected only in trace amounts, anisole does primarily act as a reversible scavenger for the highly reactive ammonium radical dication released from Selectfluor in the C−F bond-forming step. As shown for three diverse substitution patterns, the main role of anisole is to prevent, or at least reduce, the undesired addition of the ammonium radical dication to the alkene, which in turn leads to an unfavorable consumption of the arylhydrazine-derived precursors required for carbofluorination. Moreover, besides the remarkable polar effects in radical trapping, this study shows that the Selectfluor-derived nitrogen-centered radical dication may add directly to alkenes, which has not been described so far.     

Mechanistic studies of Wacker-type intramolecular aerobic oxidative amination of alkenes catalyzed by Pd(OAc)2/pyridine

Wacker-type oxidative cyclization reactions have been the subject of extensive research for several decades, but few systematic mechanistic studies of these reactions have been reported. The present study features experimental and DFT computational studies of Pd(OAc)(2)/pyridine-catalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a Pd(II)-amidate-alkene chelate with release of 1 equiv of pyridine and AcOH from the catalyst center, (2) alkene insertion into a Pd-N bond, (3) reversible β-hydride elimination, (4) irreversible reductive elimination of AcOH, and (5) aerobic oxidation of palladium(0) to regenerate the active trans-Pd(OAc)(2)(py)(2) catalyst. Evidence is obtained for two energetically viable pathways for the key C-N bond-forming step, featuring a pyridine-ligated and a pyridine-dissociated Pd(II) species. Analysis of natural charges and bond lengths of the alkene-insertion transition state suggest that this reaction is best described as an intramolecular nucleophilic attack of the amidate ligand on the coordinated alkene.     

Ruthenium-catalyzed formal [4 + 2] cycloaddition of alkynes with alkenes: formation of cyclohexenedicarboxylates via isomerization of alkynes and successive Diels-Alder reaction

Formal [4 + 2] cycloaddition of alkynes with electron-deficient alkenes, which affords 3,6-dialkyl-4-cyclohexene-1,2-dicarboxylates, was achieved using Ru(η⁶-1,3,5-cyclooctatriene)(η²-dimethyl fumarate)₂ as a catalyst. The reaction mechanism consists of two steps, isomerization of an alkyne to conjugated dienes and successive Diels-Alder reaction of the generated dienes with an electron-deficient alkene.