New 1,2,4,5-tetrakis-(N-imidazoliniummethyl)benzene and 1,2,4,5-tetrakis-(N-benzimidazoliummethyl)benzene salts as N-heterocyclic tetracarbene precursors: synthesis and involvement in ruthenium-catalyzed allylation reactions

New tetraimidazolinium and tetrabenzimidazolium salts have been prepared. Upon reaction with ^tBuOK, they generate carbene ligands, which were associated in situ to [RuCp*(MeCN)₃]PF₆ to produce new ruthenium catalysts that are active for the substitution of allylic substrates by amines, phenols, and carbonucleophiles. The influence of the N-heterocyclic core as well as that of the N-substitutents at the periphery of the salts, on reactivity and regioselectivity have been examined.     

Formal meta-specific intramolecular Friedel–Crafts allylic alkylation of phenols through a spirocyclization–dienone–phenol rearrangement cascade

Formal meta-specific intramolecular Friedel–Crafts allylic alkylation of phenols was achieved based on spirocyclization–dienone–phenol rearrangement cascades. Systematic screening of acid catalysts revealed that Sc(OTf)₃ was a highly effective catalyst for dienone–phenol rearrangement of spiro[4.5]cyclohexadienones. Using 5 mol % of Sc(OTf)₃ as the promoter, various spirocyclic substrates were transformed into the corresponding phenol derivatives in good to excellent yield. Furthermore, the one-pot sequential spirocyclization–dienone–phenol rearrangement proceeded using a palladium and scandium multi-catalytic system or a triphenylmethyl cation single-catalyst system, providing the corresponding meta-allylated phenol derivatives in excellent yield.     

Ether-directed diastereoselectivity in catalysed Overman rearrangement: comparative studies of metal catalysts

Ether-directed diastereoselectivity in Overman rearrangement of δ-methoxy and δ-TBDMSO substituted allylic trichloroacetimidates has been explored using PtCl₂, PtCl₄, AuCl and AuCl₃ catalysts in comparison with commonly used Pd(II) catalysts. For both substrates the use of PtCl₂ catalyst gave notably improved anti/syn-ratio of 1,2-aminoalcohol derivatives (anti/syn=11:1 for δ-methoxy; 6:1 for δ-TBDMSO) compared to all metal catalysts known to promote Overman rearrangement. Formation of 2-trichloromethyloxazoline was observed as a dominant side reaction in the metal catalysed rearrangement of δ-methoxy substituted allylic trichloroacetimidates considerably reducing the yield of the desired product. This side reaction was suppressed when δ-TBDMS-ether was used as a directing group.     

Synthesis of β-aryl ketones by tetraphosphine/palladium catalysed Heck reactions of 2- or 3-substituted allylic alcohols with aryl bromides

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction using 2- or 3-subtituted allylic alcohols. With these sterically congested alkenes, the selective formation of β-aryl ketones was observed when appropriate reaction conditions were used. The influence of the functional group on the aryl bromide and of the base on the selectivity is remarkable. With several substrates, much higher selectivities were obtained using NaHCO₃ instead of K₂CO₃ as base. Furthermore, this catalyst can be used at low loading with several substrates.     

Acetal formation by solvolysis of glucal-derived donor-acceptor cyclopropanes

The conversion of glucal derived donor-acceptor cyclopropanes to acetals by TiCl₄ mediated ring opening and alcohol trapping is described. Good selectivity for the alpha anomer and yields near 90% are consistently observed with aliphatic, benzylic and allylic alcohols, phenols and thiophenols. The utility of this method to prepare oligosaccharides through intermediate O,S-acetals is illustrated.     

Direct Ferrier rearrangement on unactivated glycals catalyzed by indium(III) chloride

Anhydrous InCl₃ has been shown to efficiently catalyze the Ferrier rearrangement by a direct allylic substitution of the hydroxyl group at C-3 position of glycals to afford the corresponding 2,3-unsaturated glycosides in high yields at ambient temperature. This methodology obviates the need for protecting and/or activating the C-3 hydroxyl group of glycals. The reaction works in equal ease with both 4,6-di-O-benzyl-d-glucal and 4,6-di-O-benzyl-d-galactal. The mildness of InCl₃ makes this approach compatible for glycosyl acceptors with acid labile groups. The generality of the reaction has been demonstrated with a diversity of alcohols, phenols, and sugar nucleophiles.     

Rapid microwave-assisted synthesis of phenyl ethers under mildly basic and nonaqueous conditions

A mild method for O-alkylation of phenols has been developed using stoichiometric amounts of K₂CO₃ as a base and microwave irradiation. The method is suitable for substrates that are sensitive towards strong bases or hydrolysis, or difficult to extract from an aqueous medium.     

Enantioselective synthesis of acyclic allylic esters catalyzed by a palladium/BINAP(S) system

The synthesis of chiral nonracemic acyclic allylic pivalates via the Pd-catalyzed allylic substitution of racemic allylic carbonates is presented. Good to excellent enantioselectivities (up to 90%) were observed in several cases. An extraordinarily high preference for the production of the branched regioisomeric product is seen when starting from 3-buten-2-yl and crotyl substrates. A significant kinetic resolution (k_rel = 38) of the 1,3-dimethylallyl substrate was also observed, leading to the production of esters of both enantiomers of an allylic alcohol with a single enantiomer of catalyst.     

A Mild and Highly Efficient Method for the Preparation of Silyl Ethers using Fe(HSO4)3/Et3N by Chlorosilanes

A very efficient and mild procedure for preparation of silyl ethers from benzylic, allylic, propargilic alcohols, phenols, naphtoles and some of phenolic drugs with trimethylsilylchloride (TMSCl), triethylsilylchloride (TESCl) and t‐buthyldimethylsilyl chloride (TDSCl) ethers in the presence of Fe(HSO₄)₃/Et₃N in room temperature in excellent yields is reported. This procedure also allows the excellent selectivity for silylation of alcohols and phenols.     

Peracid dependent stereoselectivity and functional group contribution to the stereocontrol of epoxidation of (E)-alkene dipeptide isosteres

Twelve Boc-protected phenylalanyl-phenylalanine and phenylalanyl-glycine trans-vinyl isosteres were epoxidised with magnesium monoperoxyphtalate hexahydrate (MMPP) and trifluoroperacetic acid, and the results have been compared with those from earlier studies on epoxidations with m-CPBA. The alkenes were synthesised in high yields with high E/Z-selectivities using either the Julia or Schlosser reactions. The formation of threo isomers was favoured in all epoxidation reactions except with CF₃CO₃H on substrates containing two allylic/homoallylic functional groups directing the peracid to opposite faces of the alkene. The switch to erythro selectivity observed with CF₃CO₃H is suggested to emanate from coordination to the allylic ester functionalities via hydrogen bond donation from the peracid. The other peracid reagents seem to be preferentially coordinated to the allylic carbamate function. The contribution of individual functional groups to the stereopreference was also investigated.     

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.     

Formyloxyacetoxyphenylmethane and 1,1-diacylals as versatile O-formylating and O-acylating reagents for alcohols

Formyloxyacetoxyphenylmethane, symmetric 1,1-diacylals and mixed 1-pivaloxy-1-acyloxy-1-phenylmethanes have been used as moisture stable O-formylating and O-acylating reagents for primary and secondary alcohols, allylic alcohols and phenols under solvent/catalyst free conditions to afford their corresponding esters in good yield.     

N-Bromosuccinimide-dibenzoyl peroxide/azabisisobutyronitrile: a reagent for Z- to E-alkene isomerization

N-Bromosuccinimide-dibenzoyl peroxide/azobisisobutyronitrile is used to carry out several types of Z- to E-alkene isomerizations. The NBS-bromination conditions are sufficient for both allylic bromination and alkene isomerization. When the allylic hydrogens are not available in substrates, only the isomerization of the alkene takes place. The present conditions for isomerization of carbon-carbon double bonds are mild and efficient.     

Copper triflate/t-BuOOAc-catalyzed amidation of allylic and benzylic acetates with sulfonamides

A copper triflate/t-BuOOAc-catalyzed amidation of allylic and benzylic acetates has been developed which is suitable for the coupling of a wide variety of functionalized sulfonamide nucleophiles with acetate electrophiles. The methodology allows for the amidation of benzylic substrates which are not further activated by an additional adjacent alkene or alkyne, enabling simple allylic acetates and primary benzylic acetates to be used as reaction partners.     

Synthesis of E-vinylogous (R)-amino acid derivatives via metal-catalyzed allylic substitutions on enzyme-derived substrates

Oxynitrilase-derived allylic (R)-cyanohydrin carbonates 3 and allylic (R)-α-hydroxy ester carbonates 6 were examined as substrates for a palladium(0)-catalyzed allylic azidation reaction. The enantioselectivities and cis/trans diastereoselectivities of the concomitant 1,3-chirality transposition step were studied. The cyano carbonates 3a–c were found to be unimpressive substrates producing γ-azido-α,β-unsaturated nitriles 4a–c with cis/trans ratios that approached unity and gave enantiomeric excesses that ranged from 57% to 85%. In contrast, ester carbonates 6a and b were excellent substrates for the reaction exclusively affording trans substitution products 7a and b in identical enantiomeric excesses of 95% ee.     

Rearrangements d'alkyl aryl ethers en phenols meta alkyles

In SbF₅-HF. ethers of para alkylated or 2.6-dialkylaled phenols give the corresponding meta alkylated phenols. For example, ethers 7, 9 and 21 give respectively the phenols 8,10, 22. Cross reactions, and use of deuterated substrates show that the mechanism implies alkylation of the O-protonated ether or phenol.     

Palladium-catalyzed desulfinylative C-C allylation of Grignard reagents and enolates using allylsulfonyl chlorides and esters

2-Methylprop-2-ene-, prop-2-ene-, 1-methylprop-2-ene-, and (E)-but-2-enesulfonyl chlorides have been used as electrophilic partners in desulfinylative palladium-catalyzed C-C coupling with Grignard reagents and sodium salts of dimethyl malonate and methyl acetoacetate. Neopentyl alk-2-ene sulfonates can also be used as electrophilic partners in desulfinylative allylic arylations and allylic alkylations. The regioselectivity of the allylic arylation and alkylation depends on the nature of the catalyst. With PdCl₂(PhCN)₂, (E)-crotyl derivatives are formed in high regioselectivity using either 1-methylprop-2-ene- or (E)-but-2-enesulfonyl chloride.     

Copper‐Catalyzed Trifluoromethylation of Trisubstituted Allylic and Homoallylic Alcohols

An efficient copper‐catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni’s reagent has been developed. This strategy, accompanied by a double‐bond migration, leads to various branched CF₃‐substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β‐H elimination is prohibited, CF₃‐containing oxetanes are isolated as the sole product.     

Pd-catalyzed asymmetric synthesis of allylic tert-butyl sulfones and sulfides: Kinetic resolution of the allylic substrate by a chiral Pd-complex

The acyclic and cyclic allylic tert-butyl sulfones 3, ent-3, 11a, 11b and 15a–c of 89–98% ee were synthesized in 40–92% yield by a Pd-catalyzed reaction of the respective allylic acetates and carbonates rac-1a, rac-1b, rac-10a, rac-10b and rac-14a–c with LiO₂St-Bu in the presence of the chiral ligands 2a, ent-2b and 12. Formation of the n-butyl sulfones 13a and 13b of 95% ee was observed. Reactions of rac-1a and 1b/ent-1b with LiO₂St-Bu in the presence of 2a and ent-2b, respectively, in THF under heterogeneous conditions were accompanied by a kinetic resolution of the allylic substrates. The faster reacting allylic substrate and the preferentially formed sulfone had the same absolute configuration. The allylic tert-butyl sulfide 17 of 92% ee was obtained in 63% yield by the Pd-catalyzed reaction of rac-1b with Me₃SiSt-Bu in the presence of ent-2b.     

Water-mediated transition-metal-free Tsuji-Trost-type reaction

The treatment of 1-acetoxy-1,3-diphenylpropene (1) by C-, O-, S- and N-nucleophiles in basic aqueous media produced the corresponding substitution products in the absence of a transition-metal catalyst. Mechanistic studies, using (S)-1 and p-MeC₆H₄CH(OAc)CHCHPh as substrates, led to propose a B_AL1 cleavage of the ester function leading to a stabilized allylic carbocation as intermediate.