Catalytic Wittig Reaction Research Articles

Catalytic wittig reactions of semi- and nonstabilized ylides enabled by ylide tuning.

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

Catalytic Wittig Reactions of Semi- and Nonstabilized Ylides Enabled by Ylide Tuning

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

First Enantioselective Catalytic Wittig Reaction

AbstractHerein we present the first catalytic enantioselective Wittig reaction. Chiral mono‐ and diphosphines were employed as catalysts for the desymmetrization of a prochiral ketone. The reaction was performed under microwave dielectric heating as well as under conventional heating. Selected catalysts led to moderate to good yields and enantioselectivities. In the presence of (+)‐1,2‐bis[(2S,5S)‐2,5‐dimethylphospholano]benzene [(S,S)‐Me‐DuPhos], an enantiomeric excess of up to 90 % was obtained.

Part I: The Development of the Catalytic Wittig Reaction

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96%) by using a precatalyst loading of 4-10 mol%. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74% yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions.

ChemInform Abstract: Breaking the Ring Through a Room Temperature Catalytic Wittig Reaction.

AbstractFirst time, acyclic phosphine oxides are used as catalysts for catalytic Wittig reactions under improved reaction conditions.

Breaking the Ring through a Room Temperature Catalytic Wittig Reaction

One ring no longer rules them all: Employment of 2.5-10 mol % of 4-nitrobenzoic acid with phenylsilane led to the development of a room temperature catalytic Wittig reaction (see scheme). Moreover, these enhanced reduction conditions also facilitated the use of acyclic phosphine oxides as catalysts for the first time. A series of alkenes were produced in moderate to high yield and selectivity.

ChemInform Abstract: Iron Carbenoid Mediated Ylide Reactions

AbstractReview: 35 refs.

Iron carbenoid-mediated ylide reactions

Electrophilic metal carbenoids, readily available from diazo compounds, prove to be good reagents for the preparation of ylides under neutral conditions. We have extended the strategy to synthesize allenes from diazoacetates with both stable and unstable ketenes in the presence of PPh3 and Fe(TCP)Cl (0.5 mol %), which provided an easy access to optically active 4,4-disubstituted allenic esters by employing enantiopure phosphines. The mechanism involving the generation of ylide through catalytic transfer of an iron(II) carbene to phosphine was confirmed. A tandem Wittig–Nazarov cyclization reaction was further developed based on these results, culminating in a straightforward method for the construction of β-methylenecyclopentenones in a multistep one-pot manner without isolation of inter-mediates. By combining AsPh3 and iron carbenoids, a catalytic Wittig reaction in toluene/water biphasic system was accomplished, affording α,β-unsaturated esters in high yields with E/Z above 50/1. Surprisingly, crotonate-derived phosphorus ylide reacted with electrophilic iron carbenoid, affording 1,1,4-trisubstituted 1,3-butadienes with high regio- and stereo-selectivities, where a new ylide generated via formal intermolecular carbenoid insertion into olefinic C–H bonds of the crotonate-derived phosphorus ylide was proposed.

Wittig without waste

The combination of a cyclic phosphine oxide and a chemoselective reducing agent are key in the discovery of a catalytic Wittig reaction.

Recycling the Waste: The Development of a Catalytic Wittig Reaction

It's all in the ring: 3-Methyl-1-phenylphospholane-1-oxide (4–10 mol %) and an organosilane reducing agent are the key components in the first Wittig reaction catalytic in phosphine. The protocol also functions well on larger scale: a reaction on a 30 mmol scale yielded 3.39 g of product, corresponding to a yield of 67 %. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.

Recycling the Waste: The Development of a Catalytic Wittig Reaction

Recycling the Waste: The Development of a Catalytic Wittig Reaction