Crotylation Of Aldehydes Research Articles

Radical Crotylation of Aldehydes with 1,3-Butadiene by Photoredox Cobalt and Titanium Dual Catalysis.

Metal-hydride hydrogen atom transfer (MHAT) has been recognized as a powerful method for alkene functionalization; however, photochemical MAT-mediated chemoselective functionalization of dienes remains undeveloped. In this study, we report a radical strategy (1e-) through MHAT using photoredox cobalt and titanium dual catalysis for aldehyde crotylation with butadiene, achieving excellent regio- and diastereoselectivity.

Allenyl Carbonate as a Butadiene Surrogate in Cobalt-Catalyzed Crotylation of Aldehydes

Allenyl carbonate was used as a 1,3-butadiene surrogate to develop a photocatalytically sustainable protocol for cobalt-catalyzed crotylation of aldehydes. The developed method tolerated a wide range of aromatic and aliphatic aldehydes with retention of functional groups under mild conditions and produced good-to-excellent yields of crotylated secondary alcohols. Based on preliminary mechanistic studies and literature precedents, a plausible mechanism is proposed.

Developing a Methodology for Catalytic Asymmetric Crotylation of Aldehydes

AbstractAsymmetric crotylation has firmly earned a place among the set of valuable synthetic tools for stereoselective construction of carbon skeletons. For a long time the field was heavily dominated by reagents bearing stoichiometric chiral auxiliaries, but now catalytic methods are gradually taking center stage, and the area continues to develop rapidly. This account focuses primarily on preformed organometallic reagents based on silicon and, to some extent, boron. It narrates our endeavors to design new and efficient chiral Lewis base catalysts for the asymmetric addition of crotyl(trichloro)silanes to aldehydes. It also covers the development of a novel protocol for kinetic resolution of racemic secondary allylboronates to give enantio- and diastereomerically enriched linear homoallylic alcohols. As a separate topic, cross-crotylation of aldehydes by using enantiopure branched homoallylic alcohols as a source of crotyl groups is discussed. Finally, the synthetic credentials of the developed methodology are illustrated by total syntheses of marine natural products, in which crotylation plays a key role in setting up stereogenic centers.1 Introduction2 Pyridine N-Oxides as Lewis Base Catalysts3 Bipyridine N,N′-Dioxides as Lewis Base Catalysts4 Chiral Allylating Reagents5 Synthetic Applications6 Concluding Remarks

Bismuth mediated barbier synthesis of α-homoallylic alcohols via a sigmatropic rearrangement in [bmim][HSO4]

A novel protocol for the Bismuth metal mediated regioselctive crotylation of aldehydes yielding α-homoallylic alcohols has been developed using 20 mol% [bmim][HSO4] as a metal activator, as well as a mediator for regioconversion from the initially formed γ-regiomer. The present protocol minimizes the use of conventional solvents and proceeds with good yields and excellent regioselectivities.

Bi(cyclopentyl)diol-Derived Boronates in Highly Enantioselective Chiral Phosphoric Acid-Catalyzed Allylation, Propargylation, and Crotylation of Aldehydes.

In this study, we disclose the catalytic addition of bi(cyclopentyl)diol-derived boronates to aldehydes promoted by chiral phosphoric acids, allowing for the formation of enantioenriched homoallylic, propargylic, and crotylic alcohols (up to >99% enantiomeric excess (ee), diastereomeric ratio (dr) >20:1). These boronate substrates provided superior enantioselectivities, allowing for the reactions to proceed with low catalyst loading (0.5-5 mol %) and reduced reaction time (15 min at room temperature for aldehyde allylboration). A wide substrate scope was exhibited, and the novel boronates provided high enantiocontrol. Reactions with substituted allylboronates and aldehydes yielded vicinal stereogenic alcohols bearing β-tertiary or quaternary carbon centers. High enantio- and diastereoselectivities were found due to the closed six-membered chair-like transition state, with backbone modifications of the boronate and its interactions with the chiral phosphoric acid being the most likely contributing factor.

Benzamidoxime-Mediated Crotylation of Aldehydes using Potassium (Z) and (E)-Crotyltrifluoroborates

A highly diastereoselective protocol for the crotylation reaction of aldehydes using potassium (Z) and (E)-crotytrifluoroborates was developed. Benzamidoxime was employed as a renewable catalyst, which was easily recovered through a simple extraction process. This method proved to be simple, fast, regio- and chemoselective for different aldehydes. The corresponding homoallylic alcohols were obtained in good to excellent yields without the need of further purification.

Chemo- and Stereoselective Crotylation of Aldehydes and Cyclic Aldimines with Allylic gem-Diboronate Ester.

We report a highly chemo- and stereoselective crotylation of aldehydes and cyclic aldimines with allylic-gem-diboronate ester as a new type of organoboron reagent. The allylic-gem-diboronate ester undergoes the crotylation with aldehydes and cyclic aldimines in excellent stereoselectivity, forming anti-5,6-disubstituted oxaborinin-2-ols or (E)-δ-boryl-anti-homoallylic amines in high efficiency. The reaction shows a wide range of substrate scope and excellent functional group tolerance. The synthetic applications of the obtained products, including stereospecific C-C, C-O, and C-Cl bond formation, are also demonstrated.

Syn-Selective crotylation of aldehydes using bismuth-crotyl bromide-(1-butyl-3-methylimidazolium bromide) combination: some synthetic applications.

The Bi-[bmim][Br] combination has been found to offer high syn-selectivity in the crotylation of aldehydes with crotyl bromide using practically stoichiometric amounts of the reagents. The room temperature ionic liquid (RTIL), [bmim][Br], activated Bi metal in the presence of oxygen to produce crotylbismuthdibromide, which reacted with the aldehydes at room temperature. The major anti-syn diastereomeric product obtained from the crotylation of (R)-cyclohexylideneglyceraldehyde was utilized for the synthesis of dictyostatin and cryptophycin segments, and (+)-cis-aerangis lactone, using standard synthetic protocols.

ChemInform Abstract: Catalytic Asymmetric Crotylation of Aldehydes: Application in Total Synthesis of (‐)‐Elisabethadione.

AbstractThe crotylation of aldehydes by trichlorocrotylsilane yields β‐methyl homoallylic alcohols with high enantioselectivity.

Catalytic asymmetric crotylation of aldehydes: application in total synthesis of (-)-elisabethadione.

A new, highly efficient Lewis base catalyst for a practical enantio- and diastereoselective crotylation of unsaturated aldehydes with E- and Z-crotyltrichlorosilanes has been developed. The method was employed as a key step in a novel asymmetric synthesis of bioactive serrulatane diterpene (-)-elisabethadione. Other strategic reactions for setting up the stereogenic centers included anionic oxy-Cope rearrangement and cationic cyclization. The synthetic route relies on simple, high yielding reactions and avoids use of protecting groups or chiral auxiliaries.

Converting chair-like transition states into zig-zag projections

A short and easy method for the conversion of chair-like transition states into zig-zag projections using planar cyclohexane structures, and also the concepts of change of bond in the plane and group swap by rotation are described. Some common reactions where this method could be used to draw products include: aldol reaction, [3,3] sigmatropic rearrangements, allylation and crotylation of aldehydes, and formation of lithium enolates.

ChemInform Abstract: A Practical Procedure of Low Valent Tin Mediated Barbier Allylation of Aldehydes in Wet Solvent.

Abstract Use of aluminium as the reducing metal in spontaneous bimetal redox reaction has been elegantly exploited for allylation/crotylation of aldehydes in wet solvent. Here, low valent tin was prepared in situ by reduction of SnCl 2 ·2H 2 O with aluminium in THF/water. The resulting low valent tin acted as an efficient mediator for allylation and crotylation of aldehydes ( 3a – q ) producing the corresponding homoallylic alcohols. The efficacy of this procedure was due to its operational simplicity, practical viability, inexpensiveness, good yields of the products and short reaction time.

ChemInform Abstract: Enantioenriched Bifunctional Crotylsilanes for the Asymmetric Synthesis of Orthogonally Protected 2‐Methyl‐1,3‐diols.

AbstractBifunctional air‐stable crotylsilane (I) undergoes highly enantio‐ and diastereoselective aldehyde crotylation followed by Ir(I)‐catalyzed double diastereoselective allylic etherification.

ChemInform Abstract: A New and More Powerfully Activating Diamine for Practical and Scalable Enantioselective Aldehyde Crotylsilylation.

AbstractA convenient one‐pot protocol employing an optically active diaminophenol activator ligand for the diastereo‐ and enantioselective allylation and crotylation of aldehydes is developed.

A practical procedure of low valent tin mediated Barbier allylation of aldehydes in wet solvent

Use of aluminium as the reducing metal in spontaneous bimetal redox reaction has been elegantly exploited for allylation/crotylation of aldehydes in wet solvent. Here, low valent tin was prepared in situ by reduction of SnCl2·2H2O with aluminium in THF/water. The resulting low valent tin acted as an efficient mediator for allylation and crotylation of aldehydes (3a–q) producing the corresponding homoallylic alcohols. The efficacy of this procedure was due to its operational simplicity, practical viability, inexpensiveness, good yields of the products and short reaction time.

Enantioenriched Bifunctional Crotylsilanes for the Asymmetric Synthesis of Orthogonally Protected 2-Methyl-1,3-diols

Enantiomerically pure α-substituted crotylsilane reagents I and ent-I undergo asymmetric aldehyde crotylation followed by Ir(I)-catalyzed diastereoselective allylic etherification to give a variety of orthogonally protected 2-methyl-1,3-diols at the synthetically useful level of yields and stereoselectivity. The reagents are air-stable and bifunctional so that they can be used in these reactions sequentially without recourse to functional group adjustments.

ChemInform Abstract: Ir(I)‐Catalyzed Enantioselective Decarboxylative Allylic Etherification: A General Method for the Asymmetric Synthesis of Aryl Allyl Ethers.

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification of aryl allyl carbonates provides aryl allyl ethers. Key to the generality and high stereoselection of the reaction is the use of the intramolecular decarboxylative allylation process and [Ir(dbcot)Cl]2 as an Ir(I) source. Ir(I)-catalyzed diastereoselective decarboxylative allylic etherification, combined with asymmetric aldehyde crotylation and cross metathesis, can furnish monoprotected 2-methyl-1,3-diols (starting from simple aldehydes) with high diastereoselectivities.

Ir(I)-Catalyzed Enantioselective Decarboxylative Allylic Etherification: A General Method for the Asymmetric Synthesis of Aryl Allyl Ethers

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification of aryl allyl carbonates provides aryl allyl ethers. Key to the generality and high stereoselection of the reaction is the use of the intramolecular decarboxylative allylation process and [Ir(dbcot)Cl](2) as an Ir(I) source. Ir(I)-catalyzed diastereoselective decarboxylative allylic etherification, combined with asymmetric aldehyde crotylation and cross metathesis, can furnish monoprotected 2-methyl-1,3-diols (starting from simple aldehydes) with high diastereoselectivities.

ChemInform Abstract: High Regiocontrol in the Zinc‐Mediated Crotylation of Aldehydes and Ketones: A Straightforward and Facile Approach to Linear Homoallylic Alcohols in DMPU.

The α-regioselectivity of carbonyl crotylation is a long-standing problem in the realm of C–C bond formation reactions. We demonstrate that zinc-mediated crotylation of aldehydes and ketones can afford α-linear homoallylic alcohols exclusively to provide a simple solution for this problem. In this context, we describe a method for the α-regioselective crotylation of aldehydes and ketones by using an easily available starting material, such as crotyl bromide, zinc dust, and the less-toxic solvent DMPU. The reaction has broad substrate scope and is highly efficient. Moreover, a metallo-[3,5]-sigmatropic rearrangement is proposed to account for the high α-regioselectivity in the zinc-mediated crotylation.

Ru-Catalyzed Asymmetric Crotylation of Aldehydes with Butadiene

Ru-Catalyzed Asymmetric Crotylation of Aldehydes with Butadiene