Selective Cobalt-Catalyzed Reduction of Terminal Alkenes and Alkynes Using (EtO)₂Si(Me)H as a Stoichiometric Reductant

While attempting to effect Co-catalyzed hydrosilylation of β-vinyl trimethylsilyl enol ethers, we discovered that, depending on the silane, solvent, and the method of generation of the reduced cobalt catalyst, a highly efficient and selective reduction or hydrosilylation of an alkene can be achieved. This paper deals with this reduction reaction, which has not been reported before in spite of the huge research activity in this area. The reaction, which uses the air-stable [2,6-bis­(aryliminoyl)­pyridine)]­CoCl₂ activated by 2 equiv of NaEt₃BH as the catalyst (0.001–0.05 equiv) and (EtO)₂SiMeH as the hydrogen source, is best run at ambient temperature in toluene and is highly selective for the reduction of simple unsubstituted 1-alkenes and the terminal double bonds in 1,3- and 1,4-dienes, β-vinyl ketones, and silyloxy dienes. The reaction is tolerant of various functional groups such as bromide, alcohol, amine, carbonyl, di- or trisubstituted double bonds, and water. Highly selective reduction of a terminal alkyne to either an alkene or alkane can be accomplished by using stoichiometric amounts of the silane. Preliminary mechanistic studies indicate that the reaction is stoichiometric in the silane and both hydrogens in the product come from the silane

A Theoretical Investigation of the Ni(II)-Catalyzed Hydrovinylation of Styrene

We report a detailed and full computational investigation on the hydrovinylation reaction of styrene with the Ni(II)-phospholane catalytic system, which was originally presumed to proceed through a cationic mechanism involving a nickel hydride intermediate. The following general features emerge from this study on a specific catalyst complex that was found to give quantitative yield and moderate selectivity: (a) the activation barrier for the initiation (18.8 kcal/mol) is higher than that for the reaction due to a low-lying square-planar pentenyl chelate intermediate originating from a Ni(II)-allyl catalyst precursor. Consequently there is an induction period for the catalysis; (b) the exit of product from the catalyst is via a <i>β-H</i>-<i>transfer</i> step instead of the usual <i>β-H elimination</i> pathway, which has a very high activation energy due to a trans effect of the phospholane ligand; (c) the turnover-limiting and enantio- determining transition state is also the β-H-transfer; (d) because of the absence of a hydride intermediate, the unwanted isomerization of the product is prevented; (e) since the enantio-discrimination is decided at the H-transfer stage itself, the configuration of the product in a catalytic cycle influences the enantioselectivity in the subsequent cycle; (f) the trans effect of the sole strong ligand in the d⁸ square-planar Ni(II), the stability of the η³-benzyl intermediate, and the availability of three coordination sites enable regioselective hydrovinylation over the possible oligomerization/polymerization of the olefin substrates and linear hydrovinylation. This work has also confirmed the previously recognized role of the hemilabile group at various stages in the mechanism

Chemoselective Reactions of (<i>E</i>)‑1,3-Dienes: Cobalt-Mediated Isomerization to (<i>Z</i>)‑1,3-Dienes and Reactions with Ethylene

In the asymmetric hydrovinylation (HV) of an <i>E</i>/<i>Z</i>-mixture of a prototypical 1,3-diene with (<i>S</i>,<i>S</i>)-(DIOP)­CoCl₂ or (<i>S</i>,<i>S</i>)-(BDPP)­CoCl₂ catalyst in the presence of Me₃Al, the (<i>E</i>)-isomer reacts significantly faster, leaving behind the <i>Z</i>-isomer intact at the end of the reaction. The presumed [<b>L</b>Co–H]⁺-intermediate, especially when <b>L</b> is a large-bite angle ligand, similar to DIOP and BDPP, promote an unusual isomerization of (<i>E</i>/<i>Z</i>)-mixtures of 1,3-dienes to isomerically pure <i>Z</i>-isomers. A mechanism that involves an intramolecular hydride addition via an [η⁴-(diene)­(<b>L</b>Co–H)]⁺ complex, followed by π–σ–π isomerization of the intermediate Co­(allyl) species, is proposed for this reaction

Cobalt-Catalyzed Enantioselective Hydroboration of α‑Substituted Acrylates

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of α-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of α-alkyl- and α-aryl- acrylates, giving β-borylated propionates. Since the C–B bonds in these compounds can be readily replaced by C–O, C–N, and C–C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of “Roche” ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in these reactions and rule out the possibility of a [L]Co–H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the β-carbon of an η4-coordinated acrylate-cobalt complex is proposed as a plausible route

Asymmetric Hydrovinylation of Vinylindoles. A Facile Route to Cyclopenta[<i>g</i>]indole Natural Products (+)-<i>cis</i>-Trikentrin A and (+)-<i>cis</i>-Trikentrin B

Vinylindoles undergo Ni­(II)-catalyzed asymmetric hydrovinylation under very mild conditions (−78 °C, 1 atm ethylene, 4 mol % catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantioselectivities. Hydroboration of the alkene and oxidation to an acid, followed by Friedel–Crafts annulation, gives an indole-annulated cyclopentanone that is a suitable precursor for the syntheses of <i>cis</i>-trikentrins and all known herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is converted into (+)-<i>cis</i>-trikentin A in four steps (Wittig reaction, alkene isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The previous synthesis of this molecule from (<i>S</i>)-(−)-malic acid involved more than 20 steps and a preparative HPLC separation of diastereomeric intermediates

Control of Selectivity through Synergy between Catalysts, Silanes, and Reaction Conditions in Cobalt-Catalyzed Hydrosilylation of Dienes and Terminal Alkenes

Readily accessible (^{<i>i‑</i>Pr}PDI)­CoCl₂ [^{<i>i‑</i>Pr}PDI = 2,6-<i>bis</i>(2,6-diisopropylphenyliminoethyl)­pyridine] reacts with 2 equiv of NaEt₃BH at −78 °C in toluene to generate a catalyst that effects highly selective anti-Markovnikov hydrosilylation of the terminal double bond in 1,3- and 1,4-dienes. Primary and secondary silanes such as PhSiH₃, Ph₂SiH₂, and PhSi­(Me)­H₂ react with a broad spectrum of terminal dienes without affecting the configuration of the other double bond. When dienes conjugated to an aromatic ring are involved, both Markovnikov and anti-Markovnikov products are formed. The reaction is tolerant of various functional groups such as an aryl bromide, aryl iodide, protected alcohol, and even a silyl enol ether. Reactions of 1-alkene under similar conditions cleanly lead to a mixture of Markovnikov and anti-Markovnikov hydrosilylation products, where the ratio of the products increasingly favors the latter, as the size of the 2,6-substituents in the iminoylaryl group becomes larger. The complex (^{<i>i‑</i>Pr}PDI)­CoCl₂ gives exclusively the linear silane for a wide variety of terminal alkenes. Mechanistic studies suggest a pathway that involves a key role for an in situ-generated metal hydride, (<b>L</b>)­Co­(I)-H. Exclusive reduction of the terminal double bond (vis-à-vis hydrosilylation) when (EtO)₂Si­(Me)H is used in the place of PhSiH₃ is explained on the basis of an alternate silane-mediated decomposition path for the linear Co­(I)-alkyl intermediate

Asymmetric Catalysis with Ethylene. Synthesis of Functionalized Chiral Enolates

Trialkylsilyl enol ethers are versatile intermediates often used as enolate surrogates for the synthesis of carbonyl compounds. Yet there are no reports of broadly applicable, catalytic methods for the synthesis of chiral silyl enol ethers carrying latent functionalities useful for synthetic operations beyond the many possible reactions of the silyl enol ether moiety itself. Here we report a general procedure for highly catalytic (substrate:catalyst ratio up to 1000:1) and enantioselective (92% to 98% major enantiomer) synthesis of such compounds bearing a vinyl group at a chiral carbon at the β-position. The reactions, run under ambient conditions, use trialkylsiloxy-1,3-dienes and ethylene (1 atm) as precursors and readily available (bis-phosphine)-cobalt­(II) complexes as catalysts. The silyl enolates can be readily converted into novel enantiopure vinyl triflates, a class of highly versatile cross-coupling reagents, enabling the syntheses of other enantiomerically pure, stereodefined trisubstituted alkene intermediates not easily accessible by current methods. Examples of Kumada, Stille, and Suzuki coupling reactions are illustrated

Catalytic Enantio­selective Hetero-dimerization of Acrylates and 1,3-Dienes

1,3-Dienes are ubiquitous and easily synthesized starting materials for organic synthesis, and alkyl acrylates are among the most abundant and cheapest feedstock carbon sources. A practical, highly enantio­selective union of these two readily available precursors giving valuable, enantio-pure skipped 1,4-diene esters (with two configurationally defined double bonds) is reported. The process uses commercially available cobalt salts and chiral ligands. As illustrated by the use of 20 different substrates, including 17 prochiral 1,3-dienes and 3 acrylates, this hetero-dimerization reaction is tolerant of a number of common organic functional groups (e.g., aromatic substituents, halides, isolated mono- and di-substituted double bonds, esters, silyl ethers, and silyl enol ethers). The novel results including ligand, counterion, and solvent effects uncovered during the course of these investigations show a unique role of a possible cationic Co­(I) intermediate in these reactions. The rational evolution of a mechanism-based strategy that led to the eventual successful outcome and the attendant support studies may have further implications for the expanding use of low-valent group 9 metal complexes in organic synthesis

Russian Nesting Doll Complexes of Molecular Baskets and Zinc Containing TPA Ligands

In this study, we examined the structural and electronic complementarities of convex <b>1</b>–Zn­(II), comprising functionalized tris­(2-pyridylmethyl)­amine (TPA) ligand, and concave baskets <b>2</b> and <b>3</b>, having glycine and (<i>S</i>)-alanine amino acids at the rim. With the assistance of ¹H NMR spectroscopy and mass spectrometry, we found that basket <b>2</b> would entrap <b>1</b>–Zn­(II) in water to give equimolar <b>1</b>–Zn⊂<b>2</b>_in complex (<i>K</i> = (2.0 ± 0.2) × 10³ M^–1) resembling Russian nesting dolls. Moreover, <i>C</i>₃ symmetric and enantiopure basket <b>3</b>, containing (<i>S</i>)-alanine groups at the rim, was found to transfer its static chirality to entrapped <b>1</b>–Zn­(II) and, via intermolecular ionic contacts, twist the ligand’s pyridine rings into a left-handed (<i>M</i>) propeller (circular dichroism spectroscopy). With molecular baskets embodying the second coordination sphere about metal-containing TPAs, the here described findings should be useful for extending the catalytic function and chiral discrimination capability of TPAs

Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control

A stereogenic center, placed at an exocyclic location next to a chiral carbon in a ring to which it is attached, is a ubiquitous structural motif seen in many bioactive natural products, including di- and triterpenes and steroids. Installation of these centers has been a long-standing problem in organic chemistry. Few classes of compounds illustrate this problem better than serrulatanes and amphi­lectanes, which carry multiple methyl-bearing exocyclic chiral centers. Nickel-catalyzed asymmetric hydro­vinylation (AHV) of vinyl­arenes and 1,3-dienes such as 1-vinyl­cycloalkenes provides an exceptionally facile way of introducing these chiral centers. This Article documents our efforts to demonstrate the generality of AHV to access not only the natural products but also their various diastereo­isomeric derivatives. Key to success here is the availability of highly tunable phosphor­amidite Ni­(II) complexes useful for overcoming the inherent selectivity of the chiral intermediates. The yields for hydro­vinylation (HV) reactions are excellent, and selectivities are in the range of 92–99% for the desired isomers. Discovery of novel, configurationally fluxional, yet sterically less demanding 2,2′-biphenol-derived phosphor­amidite Ni complexes (fully characterized by X-ray) turned out to be critical for success in several HV reactions. We also report a less spectacular yet equally important role of solvents in a metal–ammonia reduction for the installation of a key benzylic chiral center. Starting with simple oxygenated styrene derivatives, we iteratively install the various exocyclic chiral centers present in typical serrulatane [e.g., a (+)-<i>p</i>-benzo­quinone natural product, elisabetha­dione, <i>nor</i>-elisabetha­dione, helioporin D, a known advanced intermediate for the synthesis of colombiasin and elisa­pterosin] and amphi­lectane [e.g., A–F, G–J, and K,L pseudo­pterosins] derivatives. A concise table showing various synthetic approaches to these molecules is included in the Supporting Information. Our attempts to synthesize a hitherto elusive target, elisabethin A, led to a stereo­selective, biomimetic route to pseudo­pterosin A–F aglycones