Nucleophilic Allylation Research Articles

Silica Support‐Enhanced Pd‐Catalyzed Allylation Using Allylic Alcohols

AbstractThe front cover artwork for issue 20/2018 is provided by Dr. Ken Motokura at Tokyo Institute of Technology (Japan) and collaborators. The image illustrates the concerted catalysis of a Pd complex and silanol on a mesoporous silica surface for the efficient activation of allylic alcohol in the allylation of nucleophiles. See the Full Paper itself at https://doi.org/10.1002/cctc.201801097.

Silica Support‐Enhanced Pd‐Catalyzed Allylation Using Allylic Alcohols

AbstractAlthough allylation using allylic alcohol is an environmentally‐friendly method because of water being the sole byproduct in such reactions, allylic alcohol is one of the most difficult allylating agents in Pd‐catalyzed allylation of nucleophiles. In this study, we successfully developed a mesoporous silica‐supported Pd complex as an efficient catalyst for the allylation of nucleophiles using allylic alcohols as allylating agents. The allylic alcohol is activated by the silanol group on the support surface, which easily undergoes a π‐allylpalladium intermediate formation. The catalytic activity of the supported Pd complex was ca. 9 times higher than that of its homogeneous precursor Pd complex. A highest turnover number of 4500 based on Pd was achieved. Various nucleophiles and allylic alcohol derivatives could be used as substrates. Not only the detailed catalyst structure but also the reaction mechanism including the concerted activation of allylic alcohol by the Pd complex and silanol were investigated by several spectroscopic techniques, such as Pd K‐edge XAFS, solid‐state NMR, and in‐situ FT‐IR measurements.

Remote Nucleophilic Allylation by Allylrhodium Chain Walking.

Metal migration through a carbon chain is a versatile method for achieving remote functionalization. However, almost all known examples involve the overall net migration of alkylmetal species. Here, we report that allylrhodium species obtained from hydrorhodation of 1,3-dienes undergo chain walking toward esters, amides, or (hetero)arenes over distances of up to eight methylene units. The final, more highly conjugated allylrhodium species undergo nucleophilic allylation with aldehydes and with an imine to give Z-homoallylic alcohols and amines, respectively.

Deacylative Reactions: Synthetic Applications

Herein we introduce the recent developments of a new strategy based on deacylative alkylation (DaA) reactions for the generation of quaternary stereocenters based on the in situ preparation and functionalization of enolates under very mild reaction conditions. Palladium‐catalyzed deacylative allylation and benzylation reactions of carbon nucleophiles are performed with the corresponding alcohols. This methodology has been applied to the synthesis of the calcium ion channel blocker verapamil, the antiviral (+)‐hamigeran B, several oxindole precursors of esermethole, horsfiline, physostigmine, phenserine, meso‐folicanthine, meso‐chinonanthine and the dimer cyclotriptamine alkaloids. Base‐promoted deacylative reactions enable the functionalization of 2‐oxindole enolates at the 3‐position with alkyl halides and electrophilic alkenes. In the presence of oxygen or air, 3‐hydroxy‐2‐oxindoles are prepared by deacylative oxidation. Detrifluoroacylative reactions are promoted by a base generating fluoroenolates, which can participate in aldol, Mannich and Michael reactions for the preparation of important fluorinated intermediates. Finally, palladium‐catalyzed deacylative cross‐coupling of acetyl diazoacetates and phosphonates with aryl iodides let to the formation of aryl diazoacetates and phosphonates, respectively. The same process, with 2‐iodoazoarenes and 2‐iodoaryltriazenes, gives 2H‐indazoles, which are important pharmacophores.

Iterative Synthetic Strategy for Azaphenalene Alkaloids. Total Synthesis of (-)-9a epi-Hippocasine.

A new strategy for the stereoselective synthesis of alkaloids with perhydro-9b-azaphenalene skeleton has been developed. The starting material is the substituted glutarimide derivative 1, readily available in either enantiomeric form through the palladium-catalyzed asymmetric allylic alkylation of glutarimide. The strategy relies on an iterative methodology encompassing two nucleophilic allylations and two ring closing metathesis processes. The approach has been used in the first synthesis of (-)-9a- epi-hippocasine.

Coupling of Boronic Acids, 1,3-Enynes and Cyclic Imines

Key words rhodium catalysis - enantioselective nucleophilic allylation - 1,4-rhodium(I) migration - three-component coupling

Catalytic nucleophilic 'umpoled' π-allyl reagents.

After seminal Tsuji-Trost reactions (palladium catalyzed allylation of nucleophiles via π-allyl intermediates as electrophiles), the idea of reversal reactivity of π-allyl intermediates (i.e. π-allyl as nucleophiles) has been stated since the eighties. Thanks to different transition metal sources and the modification of their electronic environment through the use of additives and ligands, such 'reactivity switch' of π-allyl intermediates proved its powerfulness allowing high control in regio-, diastereo- and enantio-selectivities. These methodologies have thus emerged as efficient methods in the catalytic enantioselective allylation of carbonyl compounds and imines with a deep impact on natural product and/or drug elaboration. This tutorial review highlights the concept of 'umpoled' reactivity of π-allyl intermediates, relying on selected recent examples.

Catalytic Nucleophilic Allylation Driven by the Water-Gas Shift Reaction.

The ruthenium-catalyzed allylation of aldehydes with allylic pro-nucleophiles has been demonstrated to be an efficient means to form carbon-carbon bonds under mild conditions. The evolution of this reaction from the initial serendipitous discovery to its general synthetic scope is detailed, highlighting the roles of water, CO, and amine in the generation of a more complete catalytic cycle. The use of unsymmetrical allylic pro-nucleophiles was shown to give preferential product formation through the modulation of reaction conditions. Both (E)-cinnamyl acetate and vinyl oxirane were efficiently used to form the anti-branched products (up to >20:1 anti/syn) and E-linear products (up to >20:1 E/Z) in high selectivity with aromatic, α,β-unsaturated, and aliphatic aldehydes, respectively. Attempts to render the reaction enantioselective are highlighted and include enantioenrichment of up to 75:25 for benzaldehyde.

Enantioselective approach to indolizidine and quinolizidine scaffolds. Application to the synthesis of peptide mimics

An enantioselective approach to substituted indolizidine and quinolizidine frameworks has been developed. Key steps of the synthesis are the enantioselective, palladium-catalyzed N-allylation of an imide, the nucleophilic allylation of an acyliminium ion and a ring closing metathesis. This general strategy has been applied to the synthesis of indolizidine peptide mimics, starting from a chiral imide derived from l-aspartic acid. It was observed that the preexisting stereogenic center of this substrate has a moderate influence on the stereoselectivity of the electrophilic allylation, which is mainly determined by the sense of chirality of the catalyst.

Direct Allylic Amination of Allylic Alcohol Catalyzed by Palladium Complex Bearing Phosphine-Borane Ligand.

The direct electrophilic, nucleophilic, and amphiphilic allylations of allylic alcohol by use of a palladium catalyst and organometallic reagents such as organoborane and organozinc has been developed. The phosphine-borane compound works as the effective ligand for palladium-catalyzed direct allylic amination of allylic alcohol. Thus, with secondary amines, the reaction was completed in only 1 h, even at room temperature.

固体表面における協奏的触媒作用：金属錯体・金属カチオン・有機分子の集積による有機反応の促進

Bifunctional catalytic surface enables significant acceleration of organic reactions by concerted catalysis. For example, allylation of nucleophiles smoothly occurred on a SiO2 surface possessing both Pd complex and tertiary amine. In the case of the catalysts with Pd-bisphosphine complex and 1,4-diazabicyclo [2.2.2] octane (DABCO) on same SiO2 surface, the turnover number (TON) value based on Pd species approached up to 106000. Other reaction systems containing Rh complex and In cation for 1,4-addition of organoboronic acid and cyanation reaction of aldehyde, respectively, are also described. These SiO2- and SiO2-Al2O3-supported catalysts were characterized by several spectroscopic techniques, such as solid-state NMR, X-ray absorption fine structure (XAFS) spectroscopy, and X-ray photoelectron spectroscopy (XPS), for atomic or molecular-level understanding. Reaction mechanisms including acceleration process is also discussed based on several experiments.

Rhodium-Catalyzed Dynamic Kinetic Asymmetric Allylation of Phenols and 2-Hydroxypyridines.

Inspired by the mechanistic studies of rhodium-catalyzed atom-economic addition of carboxylate acids to allenes, a rhodium-catalyzed dynamic kinetic asymmetric allylation of different nucleophiles with racemic allylic carbonates has been developed. High regio- and enantioselectivities can be obtained under neutral conditions and, furthermore, the chemoselectivities can be controlled by different diphosphine ligands. (R,R)-QuinoxP* leads to selective O-allylation of phenols, whereas when embedding (S,S)-DIOP as the ligand, 2-naphthol is ortho-C-allylated for the first time in high enantioselectivity. To this end, hydroxypyridines can be N-allylated by Rh(I) /(S)-DTBM-Segphos via the same intermediate as in the previously reported atom-economic addition to allenes.

ChemInform Abstract: Dehydrogenation Adjacent to Carbonyls Using Palladium—Allyl Intermediates

AbstractReview: [34 refs.

ChemInform Abstract: Chain Walking of Allylrhodium Species Towards Esters During Rhodium‐Catalyzed Nucleophilic Allylations of Imines.

AbstractThe Rh‐catalyzed reaction of imines (I) and (VIII) with allyltrifluoroborates (II) is accompanied by isomerization of the Rh‐intermediates to afford homoallylic sulfamates (III) and (IX).

Dehydrogenation Adjacent to Carbonyls Using Palladium–Allyl Intermediates

Palladium–allyl chemistry has historically been used as a means of allylation of nucleophiles, as developed by Tsuji and Trost in the 1970s. Also during this decade, the Saegusa oxidation, the most prominent palladium-catalyzed dehydrogenation reaction, was developed. This Synpacts article provides a historical overview of dehydrogenation adjacent to carbonyls and our recent contribution to this area: palladium–allyl catalyzed dehydrogenation of nitriles and esters.

Synthesis of benzofuro[3,2-b]indoline amines via deamination-interrupted Fischer indolization and their unexpected reactivity towards nucleophiles.

We report the access to the benzofuro[3,2-b]indoline framework of phalarine from benzofuran-2-ones via the Fischer indolization reaction which was interrupted at the deamination step. Unexpectedly, allyl nucleophiles did not add to the aminal position of these benzofuro[3,2-b]indoline amines but to the adjacent ring junction center in the presence of trifluoroborane to deliver 3,3-disubstituted indolines containing a difluoroboron-containing six-membered ring with fluorescence properties.

Chain Walking of Allylrhodium Species Towards Esters During Rhodium‐Catalyzed Nucleophilic Allylations of Imines

AbstractAllylrhodium species derived from δ‐trifluoroboryl β,γ‐unsaturated esters undergo chain walking towards the ester moiety. The resulting allylrhodium species react with imines to give products containing two new stereocenters and a Z‐alkene. By using a chiral diene ligand, products can be obtained with high enantioselectivities, where a pronounced matched/mismatched effect with the chirality of the allyltrifluoroborate is evident.

Chain Walking of Allylrhodium Species Towards Esters During Rhodium-Catalyzed Nucleophilic Allylations of Imines.

Allylrhodium species derived from δ‐trifluoroboryl β,γ‐unsaturated esters undergo chain walking towards the ester moiety. The resulting allylrhodium species react with imines to give products containing two new stereocenters and a Z‐alkene. By using a chiral diene ligand, products can be obtained with high enantioselectivities, where a pronounced matched/mismatched effect with the chirality of the allyltrifluoroborate is evident.

ChemInform Abstract: Catalyst‐Directed Diastereo‐ and Site‐Selectivity in Successive Nucleophilic and Electrophilic Allylations of Chiral 1,3‐Diols: Protecting‐Group‐Free Synthesis of Substituted Pyrans.

AbstractA straightforward strategy for the synthesis of different diastereomers of 4‐hydroxy‐2,6‐disubstituted pyrans is described.

ChemInform Abstract: The Isomerization of Allylrhodium Intermediates in the Rhodium‐Catalyzed Nucleophilic Allylation of Cyclic Imines.

AbstractHigh enantioselectivities are obtained with chiral diene‐Rh complexes.