Domino cyclization-alkylation protocol for the synthesis of 2,3-functionalized indoles from o-alkynylanilines and allylic alcohols

A practical and efficient protocol for the one-pot synthesis of 2,3-substituted indoles was developed via a palladacycle catalyzed domino cyclization-alkylation reaction involving 2-alkynylanilines and allylic alcohols under mild conditions without any additives.     

Simple,Copper(I)-Catalyzed Oxidation of Benzylic/Allylic Alcohols to Carbonyl Compounds: Synthesis of Functionalized Cinnamates in One Pot

An environmentally benign [Cu(I)]-catalyzed oxidation of activated (benzylic/allylic) alcohols to the corresponding carbonyl compounds is presented. Interestingly, the reaction was also compatible with benzylic alcohols containing ortho-bromo substituents on the aromatic ring without competing with the expected intermolecular Buchwald coupling. Significantly, the catalytic system enables the synthesis of cinnamate-esters in a sequential domino one-pot fashion via oxidation followed by Wittig–Horner protocol.     

Copper‐Catalyzed Cyanomethylation of Allylic Alcohols with Concomitant 1,2‐Aryl Migration: Efficient Synthesis of Functionalized Ketones Containing an α‐Quaternary Center

A copper‐catalyzed alkylation of allylic alcohols by alkyl nitriles with concomitant 1,2‐aryl migration was developed. Formation of the alkyl nitrile radical was followed by its intermolecular addition to alkenes and the migration of a vicinal aryl group with the concomitant generation of a carbonyl functionality to complete the domino sequence. Mechanistic studies suggested that 1,2‐aryl migration proceeded through a radical pathway (neophyl rearrangement). The protocol provided an efficient route to functionalized ketones containing an α‐quaternary center.     

Unifying metal- and organocatalysis for asymmetric oxidative iminium activation: a relay catalytic system enabling the combined allylic oxidation of alcohols and prolinol ether catalyzed iminium reactions

A multicatalytic system consisting of tetrapropylammonium perruthenate/N-methylmorpholine N-oxide (TPAP/NMO) as oxidant, and diarylprolinol TMS-ether as chiral amine catalyst, has been developed and applied in the efficient construction of valuable chiral molecules. The one-pot domino reactions elaborated in the present study are based on the in situ generation of α,β-unsaturated aldehydes from allylic alcohols and their subsequent use in various asymmetric transformations (e.g., cyclopropanation, Michael addition, Michael addition/acetalization). TPAP as a substrate-selective redox catalyst is well tolerated by the amine catalyst and the domino reactions proceed in good yields and high enantioselectivities. The compatibility of metal and organocatalysis presented herein widens the scope of asymmetric iminium catalysis.     

Domino reactions for the synthesis of various α-substituted nitro alkenes

Efficient one-pot methods for the synthesis of variously functionalised conjugated nitro alkenes have been reported. Despite the utility in different fields of these compounds, only a few multi-step syntheses have been reported in the literature, giving the target compounds in low overall yields. α-Nitro acrylates or cinnamates, α-nitro α,β-unsaturated ketones and, most importantly, aromatic and heteroaromatic (E)- 2-nitro allylic alcohols, compounds characterised by a well-known anticancer activity, were obtained in high yields and high diastereomeric purity by a domino condensation-dehydration process.     

Unifying Metal‐ and Organocatalysis for Asymmetric Oxidative Iminium Activation: A Relay Catalytic System Enabling the Combined Allylic Oxidation of Alcohols and Prolinol Ether Catalyzed Iminium Reactions

A multicatalytic system consisting of tetrapropylammonium perruthenate/N‐methylmorpholine N‐oxide (TPAP/NMO) as oxidant, and diarylprolinol TMS‐ether as chiral amine catalyst, has been developed and applied in the efficient construction of valuable chiral molecules. The one‐pot domino reactions elaborated in the present study are based on the in situ generation of α,β‐unsaturated aldehydes from allylic alcohols and their subsequent use in various asymmetric transformations (e.g., cyclopropanation, Michael addition, Michael addition/acetalization). TPAP as a substrate‐selective redox catalyst is well tolerated by the amine catalyst and the domino reactions proceed in good yields and high enantioselectivities. The compatibility of metal and organocatalysis presented herein widens the scope of asymmetric iminium catalysis.     

Facile One-pot Transformation of 2,3-Epoxy Alcohols into Allylic Alcohols

Optically-active allylic alcohols have been frequently used as chiral building blocks for the preparation of optically pure compounds.¹ There are at present various methods for the synthesis of optically active allylic alcohols including the kinetic resolution racemic allylic alcohols,² reductive rearrangement of 2,3-epoxy alcohol by metal, halide and telluium-based chemistry.³ To our knowledge, One-pot Transformation of 2,3-epoxy alcohols into allylic alcohols, especially via epoxy iodides,is limited to Dorta's method³ using a Ph₃P,iodine, imidazole,2,6-lutidine and water system. The original Dorta's method can be successfully applied to the formation of tertiary allylic alcohols, but give unsatisfactory results in formation of secondary allylic alcohols.     

Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction

Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.     

Palladium-catalyzed deracemization of allylic carbonates in water with formation of allylic alcohols: hydrogen carbonate ion as nucleophile in the palladium-catalyzed allylic substitution and kinetic resolution

The palladium-catalyzed deracemization of racemic cyclic and acyclic allylic methyl carbonates in water in the presence of N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphophino)benzamide] proceeds with high enantioselectivities to give the corresponding allylic alcohols in high yields. This deracemization involves a palladium-catalyzed allylic substitution with the in-situ-formed hydrogen carbonate ion and an irreversible decomposition of the intermediate allylic hydrogen carbonates, with formation of the corresponding allylic alcohols. The palladium-catalyzed reaction of racemic cyclic allylic acetates with potassium hydrogen carbonate in water in the presence of the chiral bisphosphane proceeds with a highly selective kinetic resolution to give the corresponding allylic alcohols and allylic acetates.     

Allylic alkylation and ring-closing metathesis in sequence: a successful cohabitation of Pd and Ru

An allylic alkylation/ring-closing metathesis domino catalytic process, wherein a palladium and a ruthenium catalyst are concomitantly present in the reaction mixture from the outset of the reaction, is developed. Evidence for Grubbs' catalysts activity in allylic alkylation is also reported.     

One-pot synthesis and resolution of chiral allylic alcohols

Substituted α,β-unsaturated ketones were selectively reduced to the corresponding allylic alcohols under mild reaction conditions. The allylic alcohols thus obtained were kinetically resolved by lipase catalyzed transesterification in the same pot to afford chiral allylic alcohols in excellent enantioselectivity. Various lipases were screened for this one-pot transesterification of allylic alcohols. Effects of different solvent have also been studied under these conditions. Pseudomonas cepacia lipase immobilized on ceramic particles (PS-C) and on diatomaceous earth (PS-D) catalyzes this transesterification in diisopropyl ether in a highly efficient manner.     

A comparison of intrazeolite and solution singlet oxygen Ene reactions of allylic alcohols

The singlet oxygen ene reactions of four allylic alcohols and for comparison an allylic ether have been examined both in solution and in zeolite Y. Brønsted acid sites in the zeolite were shown to induce decomposition of several of the allylic alcohols. Treatment of the zeolites with pyridine removed these acid sites and allowed intrazeolite reactions of the allylic alcohols without interference from decomposition. Control reactions with an allylic alcohol that is inert to decomposition provided evidence that the presence of pyridine in the zeolite labyrinth does not influence the product composition.     

A Practical Domino‐Claisen–Cope Sequence in the Synthesis of New Blooming Citrus and Potent Floral Rose Alcohols

Fifty years after its first discovery by Alan Francis Thomas , we describe a versatile, metal and pressure‐free domino‐Claisen–Cope rearrangement using the readily available α ,β‐unsaturated aldehydes 5 or their acetals 5′ and allylic alcohols 6 . This transformation provides a convenient access to a large number of radiant citrus and floral rosy odorants. Odor profiles of novel floral rosy and citrus alcohols 13 , 14 , and 16 were studied. Compound 14ba has a floral, rosy, geranium‐like character and shows unique performance and diffusiveness. Compound 16ba has a clear main citrus odor character with a clean green grapefruit/rhubarb connotation. Both odorants have been successfully introduced to perfumery recently as Rosyfolia ™ ( 14ba ) and Pomelol ™ ( 16ba ).     

Additions of allenyl/propargyl organometallic reagents to 4-oxoazetidine-2-carbaldehydes: novel palladium-catalyzed domino reactions in allenynes

Metal-mediated carbonyl allenylation and propargylation of 4-oxoazetidine-2-carbaldehydes were investigated in aqueous environment. Different propargyl bromide and metal promoters showed varied regio- and stereoselectivities on product formation. In addition, an unprecedented one-pot stereoselective synthesis of beta-chlorinated allylic alcohols, which can also be considered as functionalized allylsilanes, has been developed, which involves tin(IV) chloride-mediated reaction of propargyltrimethylsilane and 4-oxoazetidine-2-carbaldehydes. Some of the resulting coupling products were submitted to transition metal catalyzed reactions, such as the allenic Pauson-Khand and palladium-catalyzed reactions, leading to novel fused or bridged tricyclic beta-lactams. Remarkably, a novel domino process, namely the allene cyclization/intramolecular Heck reaction was found. A likely mechanism for the cascade reaction should involve an intramolecular cyclization on a (pi-allyl)palladium complex and a Heck-type reaction.     

Photoredox-Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C−H Bond Activation

Photoredox-catalyzed isomerization of γ-carbonyl-substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C−H bond activation. This catalytic redox-neutral process resulted in the synthesis of 1,4-dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ-position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.     

Reaction of allylic and benzylic alcohols and esters with PPh3/I2: one-pot synthesis of β,γ-unsaturated compounds

The treatment of tertiary and secondary allylic alcohols containing a terminal double bond, and their acetyl derivatives, with triphenylphosphine and iodine under mild conditions leads regiospecifically and in high stereoselectivity to the corresponding primary allylic iodides, which can react ‘in situ’ with diverse nucleophiles. Primary allylic alcohols and benzyl alcohols and acetates are also transformed into the corresponding iodides under these conditions.     

From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins

A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was developed by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-allyl-3-hydroxy-2-oxindoles were prepared directly from allylic alcohols in one step with excellent yields and moderate enantioselectivities. This represents the first catalytic asymmetric allylation of ketones with allylic alcohol as the allylating agent.     

Photoredox‐Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C−H Bond Activation

Photoredox‐catalyzed isomerization of γ‐carbonyl‐substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C?H bond activation. This catalytic redox‐neutral process resulted in the synthesis of 1,4‐dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ‐position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.     

Highly selective 1,3-isomerization of allylic alcohols via rhenium oxo catalysis

Two reaction strategies are developed to promote the highly selective 1,3-isomerization of a variety of allylic alcohols using O3ReOSiPh3 as a catalyst. The first strategy utilizes substrates whose 1,3-regioisomer contains a conjugated alkene, which relies on thermodynamics to obtain high selectivity. The second strategy employs N,O-bis(trimethylsilyl)acetamide as an additive to selectively and irreversibly remove the product from the reaction equilibrium and works well for the isomerization of tertiary allylic alcohols into primary allylic alcohols containing trisubstituted alkene components. High stereoselectivity is also observed in the 1,3-isomerization of enantioenriched allylic alcohols.     

Direct preparation of allylic indium(III) reagents from allylic alcohols via a reductive transmetalation of pi-allylnickel(II) with indium(I) iodide

InI-mediated direct allylation of carbonyl compounds with allylic alcohols proceeded smoothly with catalytic amounts of Ni(acac)(2) and PPh(3) to give the corresponding homoallylic alcohols in high yields. Allylindium compounds were shown to be the real allylating agents in the present system. Substituted allylic alcohols gave branched homoallylic alcohols with syn-selectivity irrespective of the geometry of the starting allylic alcohols, whereas high anti-selectivity was observed when a bulky substituent is present in the allylic alcohols. The outcome of the diastereoselectivity is discussed on the basis of the reaction mechanism, comparing with the corresponding Pd-catalyzed version. Another distinct behavior between the Ni- and Pd-catalyzed allylation was demonstrated in the reaction of hex-1,5-diene-3,4-diol derivatives: the Pd catalyst did not give any coupling product, whereas the Ni-catalyzed InI-mediated reaction with benzaldehyde afforded the 1:1 and 1:2 adduct diols selectively depending on the reaction conditions.