Palladium-Catalyzed Low Pressure Carbonylation of Allylic Alcohols by Catalytic Anhydride Activation

A direct carbonylation of allylic alcohols has been realized for the first time with high catalyst activity at low pressure of CO (10 bar). The procedure is described in detail for the carbonylation of E-nerolidol, an important step in a new BASF-route to (−)-ambrox. Key to high activities in the allylic alcohol carbonylation is the finding that catalytic amounts of carboxylic anhydride activate the substrate and are constantly regenerated with carbon monoxide under the reaction conditions. The identified reaction conditions are transferrable to other substrates as well.     

Pd-Catalyzed allylic alkylation of secondary nitroalkanes

A Pd-catalyzed allylic alkylation of secondary nitroalkanes, using a catalytic amount of external base, was developed. Simple allyl carbonate and monosubstituted allyl carbonates were used as electrophiles, and bulky secondary nitroalkanes were used as nucleophiles. This is the first catalytic allylic alkylation of bulky secondary nitroalkanes, such as 2-nitroheptane. The use of the strong base DBU in the aprotic polar solvent DMSO is a key in realizing the high reactivity. In an attempt to develop an asymmetric reaction, 2-aryloxazoline ligand PHOX L1 gave excellent results for inducing chirality at the π-allyl moiety. As for asymmetric induction at the α-position of the NO₂ functionality, the free OH-group containing 2-aryloxazoline ligand L4 showed moderate selectivity.     

手性二茂铁类配体在钯催化不对称反应中的应用

本文综述了近10 年来手性二茂铁类配体在钯催化不对称烯丙基取代反应,包括各种不同底物的烯丙基烷基化、烯丙基胺基化和烯丙基磺酰化反应中的应用,并对其在不对称Claisen 重排、不对称Diels-Alder 反应、不对称Heck 反应、不对称羰基化、不对称氢化硅烷化和不对称碳碳键断裂等反应中的应用进行了综述,对部分反应的机理和该领域的发展前景进行了讨论。     

A regio- and stereoisomeric study of allylic alcohol fluorination with a range of reagents

A range of dehydroxyfluorination reagents was reacted with separate diastereoisomers of a chiral allylic alcohol to explore both the regio- and stereoselectivity ratios of direct versus allylic fluorination. The allylic alcohol stereoisomers gave the same predominant fluorinated diastereoisomer indicating that the reaction proceeds with a significant S_N1 component via an allylic carbocation intermediate, which is quenched by fluoride ion, predominantly from the least hindered face. None of the reagents displayed very high regio- or stereoselectivity, although in all cases the allylic fluorination products predominated.     

Syngas reactions : II. The homogeneous catalyzed carbonylation and cyclization of allylic substrates

Carbon monoxide insertion and/or addition to allylic precursors may lead to the formation of both linear and cyclic carbonylation products. In examining these competing reaction paths, rhodium, platinum, palladium and nickel-based homogeneous catalysts have been developed which are particularly useful for the selective synthesis of γ-butyrolactam, N-alkyl-2-pyrrolidones, vinylacetate and phenylacetate esters and diesters from a variety of allylic and benzylic substrates. The extension of this catalysis to the carbonylation of certain vinylic and propargyl congeners had also been considered.     

Direct and Selective Synthesis of Adipic and Other Dicarboxylic Acids by Palladium-Catalyzed Carbonylation of Allylic Alcohols

A general and direct synthesis of dicarboxylic acids including industrially important adipic acid by palladium-catalyzed dicarbonylation of allylic alcohol is reported. Specifically, the combination of PdCl₂ and a bisphosphine ligand (HeMaRaphos) promotes two different carbonylation reactions with high activity and excellent selectivity.     

Conversion of Allylic Alcohols into Allylic Nitromethyl Compounds via a Palladium-Catalyzed Solvolysis: An Enantioselective Synthesis of an Advanced Carbocyclic Nucleoside Precursor(1)

A two-step reaction sequence to homoallylic nitro compounds from allylic alcohols is presented. Ethoxy carbonylation of the alcohols with ethyl chloroformate provides the corresponding allylic ethyl carbonates in high yields. Exposure of these substrates to catalytic palladium(0) in CH(3)NO(2) initiates a reaction sequence, ionization-decarboxylation-nitromethylation, that culminates with the formation of nitroalkenes. The regio- and stereochemical outcomes of the nitromethyl allylation reaction can be explained by the behavior of the transient pi-allylpalladium complexes. This methodology serves as a centerpiece for the synthesis of an important carbocyclic nucleoside intermediate.     

Palladium complex catalyzed acylation of allylic esters with acylsilanes.

Acylation of allylic esters (2) with acylsilanes (1) in the presence of a catalytic amount (5 mol %) of a palladium complex is reported. The reaction proceeds selectively to afford beta,gamma-unsaturated ketones (3) in high yields. [Pd(eta3-C6H5CH=CHCH2)(CF3COO)]2 (4a) showed the best catalytic activity. After the reaction, formation of CF3COOSiMe3 (5a) was confirmed by 29Si NMR measurement of the resulting reaction mixture, indicating the trimethylsilyl moiety effectively traps the CF3COO leaving group from 2. The leaving group of the allylic esters affects the reaction considerably: allylic trifluoroacetate gave the best result, while the corresponding acetates and trichloroacetates did not afford any acylation products at all. Stoichiometric reaction of 4a with 1 gave acylation product 3 with a formation of 5a and Pd(0), whereas no acylation reaction took place with the corresponding acetate complex [Pd(eta3-C6H5CH=CHCH2)(CH3COO)]2 (4b). A DFT calculation suggests that interaction of high-lying HOMO of 1 and low-lying LUMO of eta3-allylpalladium trifluoroacetate intermediate 4 would be indispensable in the catalytic cycle.     

Extraction of nickel from nickel alloy by carbonylation

Carbonylation refining technology has been used to extract nickel from nickel alloy. Before carbonylation, roasting and size reduction is used as a pre-treatment method, and re-activation with H₂ is needed. During carbonylation, the addition of H₂S helps to activate the nickel surface and improve the extraction rate. The supply of H₂S does not necessarily need to be continuous. The optimum parameters for extraction of nickel are a carbonylation temperature of 70 °C, pressure of 10 bar, flow rate of 0.25–0.35 L/min and mixture of CO and H₂S as carbonylation agent. The best extraction rate of nickel can reach 99%.     

Efficient synthesis of trifluoromethyl and related trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation of amino acid derived allylic carbonates

A novel stereoselective synthetic approach to (Z)-trifluoromethylalkene dipeptide isosteres (CF(3)-ADIs) is described. Starting from readily available N-Boc-L-phenylalanine, Phe-Gly type CF(3)-ADIs were obtained through palladium-catalyzed carbonylation of allylic carbonates under CO. While the reaction of N-Boc derivatives proceeds in excellent yields but lower stereoselectivity (E: Z = 62:38-43:57), the reaction of the N, N-diBoc derivative exclusively affords the desired (Z)-isomer in 61% yield. We also present a highly stereoselective synthesis of several Phe-Gly type trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation.     

Stereoselective anti-SN2′ Mitsunobu reaction of α-hydroxy-α-alkenylsilanes

A novel silyl group-directed anti-S_N2′ reaction of allylic alcohols under Mitsunobu reaction conditions is described. The Mitsunobu reaction of α-hydroxy-α-alkenylsilanes with a TBS or TIPS group gave the anti-S_N2′ product, in which regio- and stereochemical outcomes of the reaction depended on the steric bulkiness of the silyl group.     

Allylic alkylation and amination using mixed (NHC)(phosphine) palladium complexes under biphasic conditions

A dramatic improvement of the catalytic activity was observed when a phosphine was added in allylic alkylation reactions catalyzed by (NHC)Pd(η³-C₃H₅)Cl complexes. Consequently, several palladium complexes, generated in situ from different NHC-silver complexes, [Pd(η³-C₃H₅)Cl]₂ and PPh₃, were tested in this reaction to evaluate their potential. High reaction rates and conversions could be obtained with this catalytic system in the alkylation of allylic acetates with dimethylmalonate, particularly under biphasic conditions using water/dichloromethane and KOH 1 M as the base. These conditions are experimentally more convenient and gave higher reaction rates than the classical anhydrous conditions (NaH/THF). In this system, the phosphine is essential since no conversion was obtained when it is not present. The steric hindrance of the carbene ligand has a great influence on the activity and the stability of the catalytic system. The best NHC ligands for this reaction are either 1-mesityl-3-methyl-imidazol-2-ylidene or 1-(2,6-diisopropylphenyl)-3-methyl-imidazol-2-ylidene which are less bulky among the NHC tested. These two ligands led in 5 min to a complete conversion at 20 °C. The Pd-catalyzed allylic amination reaction using (E)-1,3-diphenylprop-3-en-yl acetate and benzylamine was also tested with (NHC)(PPh₃)Pd complexes and under the biphasic conditions. This reaction was found to be slower than the alkylation with dimethylmalonate but a complete conversion could be reached in 6 h at 20 °C using K₂CO₃ 1 M as the base. NMR experiments indicated that mixed (NHC)(PPh₃)Pd complexes are formed in situ but their structure could not be established exactly.     

Palladium catalysed enantioselective asymmetric allylic alkylations using the Berens’ DIOP analogue

Berens’ DIOP analogue 1a was evaluated in a series of Pd(0) catalysed asymmetric allylic alkylations of both acyclic and cyclic substrates using both C- and N-nucleophiles. The reaction conditions were exhaustively analysed and a maximum ee of 60% was obtained using rac-1,3-diphenylpropenyl acetate 3 and malonate as the nucleophile. rac-3-Acetoxycyclohexene 5 gave inferior ee’s. Various solvents were applied including [bmim]PF₆. The results using benzylamine were comparable to those obtained using malonate. For 3, in all cases the reaction exclusively gave the branched alkylated product 4 and allylic amine 8, with no trace of their linear regioisomers. The [allylPd-1a]BF₄ complex 7 was prepared, characterised and screened in the asymmetric allylic alkylation of rac-1,3-diphenylpropenyl acetate 3. It was also immobilised on montmorillonite K-10 support and preliminary solid phase reactions were conducted with 3.     

Palladium-catalyzed decarboxylative aminocarbonylation with alkynoic acid and tertiary amine for the synthesis of alkynyl amide

We developed a method for the synthesis of alkynyl amides via the carbonylation of alkynoic acids and C-N activation of tertiary amines. The reaction of alkynoic acid and tertiary amine with carbon monoxide using a palladium catalyst in the presence of oxygen, KI, and K₃PO₄, gave the desired alkynyl amides in good yields.     

Ketene as a Reaction Intermediate in the Carbonylation of Dimethyl Ether to Methyl Acetate over Mordenite

Unprecedented insight into the carbonylation of dimethyl ether over Mordenite is provided through the identification of ketene (CH₂CO) as a reaction intermediate. The formation of ketene is predicted by detailed DFT calculations and verified experimentally by the observation of doubly deuterated acetic acid (CH₂DCOOD), when D₂O is introduced in the feed during the carbonylation reaction.     

Sodium nitrite (NaNO2) catalysed iodo-cyclisation of alkenes and alkynes using molecular oxygen

We have developed a convenient iodo-cyclisation reaction using NaNO₂ as catalyst and molecular oxygen as the terminal oxidant. The reactive species, acetyl hypoiodite (IOAc), was generated in situ from TBAI and AcOH. The iodo-cyclisation reaction with a range of alkenes and alkynes gave good to excellent yields. Iodo-amination products can also be obtained using carbamates prepared from commercially available allylic alcohols and alkynic alcohols.     

Generation and reaction of heteroaromatic zirconocene: synthetic application to polycyclic heterocycles

Heteroaromatic zirconocene intermediates were generated by the reaction of ‘Cp₂Zr’ with alkoxymethyl-(TMS-ethynyl)-indole, -benzofuran or -benzothiophene derivatives under mild conditions in moderate to good yields. Copper-catalyzed C-C bond formation of the zirconocene intermediate with allylic halides gave allylation products, which were transformed into heterocyclic dienes through enyne metathesis. Preliminary Diels-Alder reaction of the dienes with DMAD showed notable site selectivity.     

Aromatic allylation via diazotization: variation of the allylic moiety and a short route to a benzazepine derivative

A continued study of the recently discovered diazotizative allylation (DiazAll) reaction of aniline derivatives is reported. Several allyl reagents, commonly used in radical allylation reactions, were evaluated, and some of these reagents resulted in allylation when used in the DiazAll reaction. The best result was obtained with allyl bromide. Substituted allylic bromides gave the corresponding allyl aromatic compounds in poor to excellent yields. In comparison with an established method for aromatic allylation, the DiazAll reaction performed well and was superior when a more complex allylic bromide was used. Finally, a new allylation-bromocyclization reaction was demonstrated and used in the synthesis of a known inhibitor of phenylethanolamine N-methyltransferase (PNMT), an enzyme involved in the biosynthesis of adrenaline.     

Heterocyclic Spiro-naphthalenones. Part I: Synthesis and reactions of some spiro [(1 H-naphthalenone)-1,3′-piperidines]

The title compounds 14–16 were obtained via an intramolecular Mannich condensation by treating 11–13 with CH₂O at RT. The unsaturated ketones 14 and 15 were reduced to the allylic alcohols 18 and 19 respectively. Ring cleavage of compound 18 on treatment with 2N HCl gave the substituted aminopropanol 20 . The allylic alcohols 18 and 19 were hydrogenated to 22 and 23 respectively. With CH₂O, the amino-alcohol 23 gave the methano-naphthoxazocine 24 , whereas 22 and 23 , on heating in polyphosphoric acid (PPA), afforded the naphthazepines 25 and 26 respectively. With organolithium compounds, the unsaturated ketones 14 and 16 gave the teriary allylic alcohols 27–29 , which were hydrogenated and dehydrated to the olefins 36–40 ; these were cyclized via an intramolecular alkylation to the methanodibenzo-octahydrocyclooctapyridines 41–43 . On heating in PPA, the allylic alcohol 29 was converted into the naphthazepine 44 . With CH₂O, the naphthol 49 gave the naphthoxazocine 50 , in equilibrium with the spiro-naphthalene-pyrrolidinone 51 in solution. Finally, in the presence of CH₂O, the naphthazepine 57 afforded the methano-naphthazepinone 58 , which, by a 4-stage degradation, was transformed to the benzisoquinoline 62 .     

Carbonylation of Olefins under Mild Temperature Conditions in the Presence of Palladium Complexes

During a search for catalysts that allow carbonylation reactions on olefins to proceed below 100 °C, complex palladium(II ) compounds having the formula L_mPdX_n were found to be catalytically active. L denotes a ligand such as a phosphine, nitrile, amine, or olefin, X is an acid residue, and m+n is 3 or 4. The catalysts permit the carbonylation of heat-sensitive compounds, as well as selective carbonylation of polyunsaturated olefins. The new process can also be carried out on the industrial scale, as is shown by the carbonylation of cyclododecatriene