Iridium-catalyzed allylic vinylation and asymmetric allylic amination reactions with o-aminostyrenes

An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.     

烯丙基保护基在多羟基化合物中的应用

烯丙基保护基由于能够在温和的反应条件下,在羟基、氨基等基团中引入和脱除,并且具有很好的区域选择性和化学选择性,因此被广泛应用于有机合成中。本文介绍了烯丙基保护基的发展历史,综述了烯丙保护基对多羟基化合物中不同羟基的选择性保护应用,并阐述了烯丙保护基的引入和脱除的机理及方法。     

Direct palladium/carboxylic acid-catalyzed allylation of anilines with allylic alcohols in water

The direct activation of C-O bonds in allylic alcohols in water as a suspension medium by palladium complexes has been accelerated by carrying out the reactions in the presence of a carboxylic acid. The palladium-catalyzed allylation of anilines using allylic alcohols directly gave allylic anilines in good yields.     

Silicon‐Directed Rhenium‐Catalyzed Allylic Carbaminations and Oxidative Fragmentations of γ‐Silyl Allylic Alcohols

A highly regioselective allylic substitution of β‐silyl allylic alcohols has been achieved that provides the branched isomer as a single product. This high level of regiocontrol is achieved through the use of a vinyl silane group that can perform a Hiyama coupling providing 1,3‐disubstituted allylic amines. An unusual oxidative fragmentation product was also observed at elevated temperature that appears to proceed by a Fleming–Tamao‐type oxidation–elimination pathway.     

Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part II. Scope and applications.

An enantioselective synthesis of allylic esters has been achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently induced the alkylation process with a variety of nucleophiles to provide allylic esters as products in good yield. High regio- and enantioselectivities were observed in the alkylation with most nucleophiles derived from malonate, whereas a modest level of ee's was obtained in the reactions with less reactive nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow addition procedure proved effective, leading to significantly improved ee's. The utility of the alkylation products was demonstrated by several synthetically useful transformations including allylic isomerizations, allylic alkylations, and Claisen rearrangements. Using these reactions, the chirality of the initial allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds in a predictable fashion with high stereochemical fidelity. The conversion of gem-diesters to chiral esters by the substitution reaction is the equivalent of an asymmetric carbonyl addition by stabilized nucleophiles. In conjunction with the subsequent reactions that occur with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a double allylic transformation.     

Acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis of terminal alkynes: scope, application, and mechanistic insights

An interesting acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis has been found. Ring-closing enyne metathesis of terminal alkynes possessing an allylic hydroxy group proceeded smoothly without the ethylene atmosphere generally necessary to promote the reaction. The synthesis of (+)-isofagomine with the aid of this efficient reaction has been demonstrated. Mechanistic studies of the acceleration effect were also carried out. Results of NMR studies suggested that the reaction proceeded via an "ene-then-yne" pathway. Kinetic studies indicated switching of the rate-determining step as a consequence of the presence of an allylic hydroxy group. These results suggest acceleration of the reentry step of Ru-carbene species by the allylic hydroxy group.     

Allylic etherification via Ir(I)/Zn(II) bimetallic catalysis

[reaction: see text] An efficient allylic etherification of aliphatic alcohols with allylic carbonates has been achieved by an iridium catalysis using stoichiometric zinc alkoxides or a two-component bimetallic catalytic system where the Ir(I) catalyst acts on allylic carbonates to generate electrophiles while aliphatic alcohols are separately activated by Zn(II) coordination to function as nucleophilies. This reaction occurs with complete regiospecificity and tolerates a wide range of functional groups.     

Pentamethylcyclopentadienyl-ruthenium catalysts for regio- and enantioselective allylation of nucleophiles

Ruthenium(II) complexes containing the pentamethylcyclopentadienyl ligand efficiently perform the activation of allylic carbonates and halides to generate cationic and dicationic ruthenium(IV) complexes. This activation has been transferred as a key step to the catalytic allylation of nucleophiles. The structural and electronic properties of the allylic moieties lead to the regioselective formation of chiral products resulting from nucleophilic addition to their most substituted terminus. The catalytic activity of various Ru(Cp*) precatalysts in several allylic substitutions by C and O nucleophiles will be presented. The enantioselective version that has been demonstrated by using optically pure bisoxazoline ligands will also be discussed.     

Cu(I)-catalyzed, α-selective, allylic alkylation reactions between phosphorothioate esters and organomagnesium reagents

Regiocontrol of allylic alkylation reactions involving hard nucleophiles remains a significant challenge and continues to be an active area of research. The lack of general methods in which α-alkylation is favored underscores the need for the development of new processes for achieving this type of selectivity. We report that Cu(I) catalyzes the allylic substitution of phosphorothioate esters with excellent α-regioselectivity, regardless of the nature of the Grignard reagent that is used. To the best of our knowledge, the Cu-catalyzed allylic alkylation of phosphorothioate esters has never been described. We have also developed a simple protocol for inducing high α selectivity starting from secondary allylic halides. This is accomplished by using sodium phosphorothioates as an additive.     

Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.     

Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents

The synthesis of a family of farnesol analogues, incorporating aromatic rings, has been achieved in high yields through the development of a regioselective coupling of allylic tetrahydropyranyl ethers with organometallic reagents. The allylic THP group is displaced readily by Grignard reagents in the presence of Cu(I) halides but is stable in the absence of added copper. Thus, an allylic THP group can fulfill its traditional role as a protecting group or serve as a leaving group depending on reaction conditions. An improved synthesis of (2E,6E)-10,11-dihydrofarnesol also has been accomplished using this methodology, and some preliminary studies on the reactivity and regioselectivity of THP ether displacements were conducted. The farnesol analogues reported herein may be useful probes of the importance of nonbonding interactions in enzymatic recognition of the farnesyl chain and allow development of more potent competitive inhibitors of enzymes such as farnesyl protein transferase.     

Recherches dans la série des cyclitols,XL. Préparation de cyclopentane-triols et de cyclopentène-triols et -diols

Two as yet unknown cyclopentene-triols have been prepared. The replacement of the halogen of cyclopentene derivatives brominated in the allylic position has been investigated. In the presence of dimethyl sulfoxide and sodium hydrogen carbonate, the bromine of some of the above mentioned allylic derivatives or the tosyloxy group of a dibenzoyloxy-monotosyloxy-cyclopentane derivative is replaced by a hydroxyl group without formation of any keto compound. The mechanism of action of the substitution agents is discussed.     

Palladium-Catalyzed Branch- and Z-Selective Allylic C−H Amination with Aromatic Amines

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C−H bonds and commonly available amines is a major synthetic challenge. An allylic C−H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.     

Tin powder‐promoted diastereoselective allylation of chiral acylhydrazones

An efficient method for the allylation of chiral acylhydrazones derived from aldehydes has been developed to give the corresponding allylic hydrazides in good yields and diastereoselectivities. The method uses a combination of tin powder and allylic bromide as allylation system, which avoids the use of toxic allylic stannanes while retaining their merits.     

Catalytic Oxidative Trifluoromethoxylation of Allylic C−H Bonds Using a Palladium Catalyst

A catalytic intermolecular allylic C−H trifluoromethoxylation reaction of alkenes has been developed based on the use of a palladium catalyst, CsOCF₃ as the trifluoromethoxide source, and benzoquinone as the oxidant. This reaction provides an efficient route for directly accessing allylic trifluoromethoxy derivatives with excellent regioselectivities from terminal alkenes via an allylic C−H bond activation process.     

From allylic alcohols to aldols through a new nickel-mediated tandem reaction: synthetic and mechanistic studies

Nickel hydride type complexes have been successfully developed as catalysts for the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes. Optimization of the reaction conditions has shown that a cocatalyst, such as MgBr2, has a very positive effect on the kinetics of the reaction and in the yields of aldols. Under such optimized conditions {[NiHCl(dppe)] + MgBr(2) at 3-5 mol %)}, this reaction affords the aldols in good to excellent yields. It is a full-atom-economy-type reaction that occurs under mild conditions. Furthermore, it has a broad scope for the allylic alcohols and it is compatible with a wide range of aldehydes, including very bulky derivatives. The reaction is completely regioselective, but it exhibits a low stereoselectivity, except for allylic alcohols with a bulky substituent at the carbinol center. The use of chiral nonracemic catalysts was not successful, affording only racemic compounds. However, it was possible to use asymmetric synthesis for the preparation of optically active aldols. Various mechanistic studies have been performed using, for instance, a deuterated alcohol or a deuterated catalyst. They gave strong support to a mechanism involving first a transition-metal-mediated isomerization of the allylic alcohol into the free enol, followed by the addition of the latter intermediate onto the aldehyde in an "hydroxyl-carbonyl-ene" type reaction. These results confirm that allylic alcohols can be considered as new and useful partners in the development of the aldol reaction.     

Platinum-catalyzed allylation of aminonaphthalenes with allylic acetates in water

The activation of C-O bonds in allylic acetates in water as a suspension medium has been accelerated by carrying out the reactions in the presence of platinum complexes associated with ligands. The platinum-catalyzed allylation of aminonaphthalenes using allylic acetates gave the corresponding N-allylic aminonaphthalenes in good yields.     

Palladium-catalyzed allylation of acidic and less nucleophilic anilines using allylic alcohols directly

The direct activation of C-O bonds in allylic alcohols by palladium complexes has been accelerated by carrying out the reactions in the presence of titanium(IV) isoproxide and 4 A molecular sieves. The acidic and less nucleophilic anilines such as diphenylamine, phenothiazine, 4-cyanoaniline, and nitroanilines are efficiently allylated under palladium catalysis using allylic alcohols as allylating reagents.     

Highly efficient and regioselective allylic amination of allylic alcohols catalyzed by [Mo3PdS4] cluster

A highly efficient and regioselective allylation reaction of amines with allylic alcohols under mild conditions catalyzed by the cubane-type sulfido cluster [(Cp∗Mo)₃S₄Pd(dba)][PF₆] with H₃BO₃ as an additive has been developed. A variety of amines and allylic alcohols are investigated, and in the case of allylic alcohols bearing substituents at either α- or γ-position only linear allylic amination products are obtained.     

Fe-Catalyzed Amidation of Allylic Alcohols by Borrowing Hydrogen Catalysis

Allylic amines are useful building blocks in organic synthesis, so the development of green and efficient methods for the preparation of allylic amines are of great importance. An Fe-catalyzed amidation of allylic alcohols with chiral tert-butylsulfinamide has been developed. With water as the only by-product, a range of synthetically useful chiral sulfinamide olefin derivatives (30 examples) were obtained under mild reaction conditions. The reaction can be performed on a gram-scale, and the products could serve as chiral ligands for asymmetric catalysis. Mechanistic studies suggest that the reaction proceeds by an Fe-catalyzed borrowing hydrogen process, which is different from most of the reported allylic amination reactions.