Photocatalytic Metal Hydride Hydrogen Atom Transfer Mediated Allene Functionalization by Cobalt and Titanium Dual Catalysis

Catalytic metal hydride hydrogen atom transfer (MHAT) reactions have proven to be a powerful method for alkene functionalization. This work reports the discovery of Co-porphines as highly efficient MHAT catalysts with a loading of only 0.01 mol % for unprecedented chemoselective allene functionalization under photoirradiation. Moreover, the newly developed bimetallic strategy by the combination of photo Co-MHAT and Ti catalysis enabled the successful carbonyl allylation with a wide range of amino, oxy, thio, aryl, and alkyl-allenes providing expedient access to valuable β-functionalized homoallylic alcohols in over 100 examples with exceptional regio- and diastereoselectivity. Mechanism studies and DFT calculations supported that selectively transferring hydrogen atoms from cobalt hydride to allenes and generating allyl radicals is the key step in the catalytic cycle.     

Highly chemoselective and stereocontrolled access to 6-alpha-allyl penicillanates

Treatment of 6-bromo penicillanates with allyltributyltin under free-radical conditions results in the formation of 6-alpha allyl derivatives.     

Organoselenium mediated asymmetric cyclizations. Synthesis of enantiomerically pure 1,6-dioxaspiro[4.4]nonanes

The asymmetric cyclization of 1-hydroxyoct-7-en-4-one, promoted by camphorselenenyl tetrafluoroborate, generated from camphor diselenide and silver tetrafluoroborate in dichloromethane at room temperature, afforded a mixture of two diastereoisomeric E- and two diastereoisomeric Z-2-[(camphorseleno)methyl]-1,6-dioxaspiro[4.4]nonanes. These were separated by medium pressure liquid chromatography and then deselenenylated with triphenyltin hydride and AIBN to give enantiomerically pure 2-methyl-1,6-dioxaspiro[4.4]nonanes. The camphorseleno group was also substituted by an allyl function using allyltributyltin in the presence of AIBN.     

Synthesis of Hydroxy-Functional PMMA Macromonomers by Anionic Polymerization

Living anionic polymerization has been utilized to synthesize hydroxy end-functionalized PMMA macromonomers with styryl or allyl functionalities as the polymerizable end-groups. Protected hydroxy-functionalized alkyl lithium initiators have been used to initiate anionic polymerization of MMA. Subsequently the living chains with protected hydroxyl function have been terminated using 4-vinylbenzyl chloride (4-VBC) or allyl methacrylate (ALMA) to form α-hydroxy-ω-styryl and α-hydroxy-ω-allyl PMMA, respectively. These protected hydroxy-functionalized PMMA macromonomers have been characterized by GPC and ¹H-NMR. Termination using 4-VBC led to 50% functionalization, whereas that using allyl methacrylate led to 100% functionalization of the hydroxy-PMMA.     

Cobalt‐Catalyzed sp2‐C−H Activation: Intermolecular Heterocyclization with Allenes at Room Temperature

The reactivity of allenes in transition‐metal‐catalyzed C?H activation chemistry is governed by the formation of either alkenyl–metal (M–alkenyl) or metal–π‐allyl intermediates. Although either protonation or a β‐hydride elimination is feasible with a M–alkenyl intermediate, cyclization has remained unexplored to date. Furthermore, due to the increased steric hindrance, the regioselectivity for the intramolecular cyclization of the metal–π‐allyl intermediate was hampered towards the more substituted side. To address these issues, a unified approach to synthesize a diverse array of biologically and pharmaceutically relevant heterocyclic moieties by cobalt‐catalyzed directed C?H functionalization was envisioned. Upon successful implementation, the present strategy led to the regioselective formation of dihydroisoquinolin‐1(2H)‐ones, isoquinolin‐1(2H)‐ones, dihydropyridones, and pyridones.     

Stille reaction over cis-halocyclohexadienediol derivatives

Stille reaction was performed with several halo cis-diol derivatives by reaction with allyltributyltin in the presence of a palladium catalyst forming allyl cis-dihydrodiol derivatives. These couplings were conducted with conventional heating as well as with microwave irradiation. Allylbenzene cis-dihydrodiol was obtained with excellent yield using mild conventional heating. However, if the diol moiety is protected with the isopropylidene group, the expected product is obtained only under microwave irradiation. The unusual reactivity observed for the polyoxygenated derivatives suggests assistance of the free hydroxyls in the catalytic cycle.     

Selenium promoted synthesis of enantiopure pyrrolidines starting from chiral aminoalcohols

Starting from commercially available enantiomerically pure aminoalcohols and using simple conversions promoted by organoselenium reagents, several enantiomerically pure substituted pyrrolidines were prepared. After double protections (R)- or (S)-2-phenylglycinols were converted into the β-amino selenides by displacing the tosyl group with phenyl selenolate anions. The phenylseleno group was then substituted by an allyl group by treatment with allyltributyltin and AIBN. The reaction of these allylic derivatives with electrophilic phenylselenium reagents afforded selenium containing pyrrolidines as the result of a 5-exo-trig cyclization. The pyrrolidine derivatives thus obtained were reductively deselenylated with triphenyltin hydride and AIBN. Moreover, the selenides were converted into the selenones, which easily gave substitution with different nucleophiles. Enantiopure 2,5-pyrrolidines containing azido, methylthio, cyano and iodo groups were thus obtained.     

Synthesis of per-substituted hydrophilic and hydrophobic ��-cyclodextrin derivatives

The aim of this work was to synthesize new cyclodextrin derivatives from native ??-cyclodextrin by allylation reactions and indium metal in aqueous and organic medium. The resulted products could be used to prepare a new hydrophilic pharmaceutical active ingredient. A hydrophobic derivative can also be prepared by the same method. Indeed, the allylation reactions allow the creation of a stereogenic centers and the introduction of an allyl group lead to development of various functionalization of CD sites. Natural ??-cyclodextrin was treated with allyl bromide and sodium hydride in dimethylformamide (DMF) at room temperature, which resulted in the formation of O-perallylated ??-cyclodextrin A₁ (98%). Through successive reactions of oxidation, reduction and allylation, the latter was converted into per 2, 3, 6-tri-O-(2-hydroxypent-4-enyl) ??-cyclodextrins A₄ (40%). Others derivates of CD type B₃ and C₃ were synthesized by series of reaction to give multifunctionalized cyclodextrins with yield of 25 and 30%, respectively.     

A novel approach to functionalization of allyl aglycon. Effective synthesis of selectively protected 2-aminoethyl lactoside, a common building block for the synthesis of carbohydrate chains of glycolipids

A novel approach to the functionalization of aglycon in allyl glycosides is described. The method comprises ozonolysis of the double bond in the allyl group, leading to the corresponding aldehyde, and subsequent transformation of the latter into the corresponding oxime, which is finally reduced to give the amine. The efficiency of this synthetic sequence (yield ∼90%) is exemplified by the transformation of two allyl lactoside derivatives into selectively protected 2-aminoethyl lactosides. The latter are convenient common building blocks for the synthesis of carbohydrate chains of glycolipids that have a lactose unit at the reducing end. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1308–1313, July, 2000.     

Synthesis of allyl end‐block functionalized poly(ε‐caprolactone)s and their facile post‐functionalization via thiol–ene reaction

A simple and facile strategy for the functionalization of commercial poly(ε‐caprolactone) diols (PCLs) with pendant functionalities at the polymer chain termini is described. Well‐defined allyl‐functionalized PCLs with varying numbers of allyl end‐block side‐groups were synthesized by cationic ring‐opening polymerization of allyl glycidyl ether using PCL diols as macroinitiators. Further functionalization of the allyl‐functionalized PCLs was realized via the UV‐initiated radical addition of a furan‐functionalized thiol to the pendant allyl functional groups, showing the suitability for post‐modification of the PCL materials. Changes in polymer structure as a result of varying the number of pendant functional units at the PCL chain termini were demonstrated. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 928–939     

Cobalt-catalyzed multisubstituted allylation of the chelation-assisted C–H bond of (hetero)arenes with cyclopropenes

Cyclopropenes are highly strained three-membered carbocycles, which offer unique reactivity in organic synthesis. Herein, Cp*Co^III-catalyzed ring-opening isomerization of cyclopropenes to cobalt vinylcarbene has been utilized for the synthesis of multisubstituted allylarenes via directing group-assisted functionalization of C–H bonds of arenes and heteroarenes. Employing this methodology, various substituents can be introduced at all three carbons of the allyl moiety with high selectivity. The important highlights are excellent functional group tolerance, multisubstituted allylation, high selectivity, gram scale synthesis, removable directing group, and synthesis of cyclopenta[b]indoles. In addition, a potential cobaltocycle intermediate was identified and a plausible mechanism is also proposed.

Cp*Co^III-catalyzed ring-opening isomerization of cyclopropenes to cobalt vinylcarbene has been utilized for the synthesis of multisubstituted allylarenes via directing group-assisted functionalization of C–H bonds of arenes and heteroarenes.     

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh₃)Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh₃)Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt-catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.     

Mechanistic aspects of reductions of allylic ethers and acetates with organocuprates

The rate of substitution to reduction has been investigated for reactions of three phenyl-substituted allylic ethers and the corresponding acetates with EtMgBr plus 10 or 25% copper(I) bromide in THF. It is found that the relative amount of reduction increases with increased electron delocalization in the postulated copper(III)-bound allyl ligand, and is also dependent on the nature of the leaving group; methoxy giving much more reduction product than acetoxy. Furthermore, for one acetate investigated there was more reduction at −65° than at −25°C. The results are interpreted in terms of relative binding strength of allyl ligands to a copper(III) intermediate.     

On the Orthogonality of Two Thiol‐Based Modular Ligations

The chemoselectivity of two thiol‐based modular ligations operating under mild conditions is assessed. For this purpose, a macromolecular scaffold possessing allyl and pentafluorophenyl groups in two distinct parts is employed, which enables facile characterization by NMR spectroscopy (¹H and ¹⁹F) and size‐exclusion chromatography. By using appropriate triggers (introduction of a base or light irradiation), it is possible to direct thiols to an arbitrarily chosen part of the scaffold, without any change to the other part and with no involvement of protecting group chemistry. Dual functionalization experiments are achieved by applying these triggers consecutively with no consideration of the reaction sequence order, evidencing full bidirectionality. A set of one‐pot, purification‐free procedures that enable near‐quantitative to full dual functionalization in (very) short reaction times (17–180 min) is also presented.     

Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.     

和厚朴酚电化学还原机理的研究

用量子化学AM1、PM3方法研究了和厚朴酚分子的电化学还原反应机理.结果表明,和厚朴酚分子电还原的基团为两个烯丙基的双键,其中邻位烯丙基优先被还原,对位次之,整个还原反应中和厚朴酚得到4e和4H⁺,使两个烯丙基饱和,计算结果较好地说明了实验事实.     

Quantitative preparation of allyl telechelic polyisobutylene under reflux conditions

Allyl telechelic polyisobutylene (allyl‐PIB‐allyl) is of great commercial and scientific interest produced by living polymerization of isobutylene followed by functionalization (allylation with allyltrimethylsilane) under external cooling, typically to ?78 °C. Cooling is cumbersome and costly, and temperature control is far from ideal. Herein we describe the quantitative preparation of allyl‐PIB‐allyl under ideal internal temperature control at ～?40 °C using refluxing propane/methyl chloride mixtures. The exact composition of the nonpolar/polar solvents and polymerization time crucially affect product quality. Well‐defined allyl‐PIB‐allyl is obtained using 60/40 (v/v) refluxing propane/methyl chloride and terminating not more than 5 min after monomer depletion. In pure refluxing propane or methyl chloride, or at longer reaction times, byproducts form that compromise product quality. A mechanism is presented to explain the observations. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 1784–1789     

Distal Allylic/Benzylic C−H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes

Regio- and stereoselective distal allylic/benzylic C−H functionalization of allyl and benzyl silyl ethers was achieved using rhodium(II) carbenes derived from N-sulfonyltriazoles and aryldiazoacetates as carbene precursors. The bulky rhodium carbenes led to highly site-selective functionalization of less activated allylic and benzylic C−H bonds even in the presence of electronically preferred C−H bonds located α to oxygen. The dirhodium catalyst Rh₂(S-NTTL)₄ is the most effective chiral catalyst for triazole-derived carbene transformations, whereas Rh₂(S-TPPTTL)₄ works best for carbenes derived from aryldiazoacetates. The reactions afford a variety of δ-functionalized allyl silyl ethers with high diastereo- and enantioselectivity. The utility of the present method was demonstrated by its application to the synthesis of a 3,4-disubstituted l -proline scaffold.     

L‐arabinitol‐based functional polyurethanes

Three new polymerizable diols, based on mono‐, di‐, and tri‐O‐allyl‐L ‐arabinitol derivatives, were prepared from L ‐arabinitol as versatile materials for the preparation of tailor‐made polyurethanes with varied degrees of functionalization. Their allyl functional groups can take part in thiol‐ene reactions, to obtain greatly diverse materials. This “click” reaction with 2‐mercaptoethanol was firstly studied on the highly hindered sugar precursor 2,3,4‐tri‐O‐allyl‐1,5‐di‐O‐trityl‐L ‐arabinitol, to apply it later to macromolecules. A polyurethane with multiple pendant allyl groups was synthesized by polyaddition reaction of 2,3,4‐tri‐O‐allyl‐L ‐arabinitol with 1,6‐hexamethylene diisocyanate, and then functionalized by thiol‐ene reaction. The coupling reaction took place in every allyl group, as confirmed by standard techniques. The thermal stability of the novel polyurethanes was investigated by thermogravimetric analysis and differential scanning calorimetry (DSC). This strategy provides a simple and versatile platform for the design of new materials whose functionality can be easily modified. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Iron-facilitated direct oxidative C-H transformation of allyl arenes to alkenyl aldehydes

A direct oxidative approach to alkenyl aldehydes from allyl arenes via allyl sp³ C-H functionalization was disclosed. An inexpensive iron catalyst was employed to facilitate this transformation. The mechanistic studies indicate that the cleavage of the allyl sp³ C-H bond is involved in the rate-determining step.