Lewis acid-catalyzed Csp3–H functionalization of methyl azaarenes with α-trifluoromethyl carbonyl compounds

A Lewis acid promoted Csp³–H bond functionalization of methyl azaarenes with α-trifluoromethylated carbonyl compounds is described. Catalytic amounts of Yb(OTf)₃ provided a straightforward access to the corresponding trifluoromethylated alcohols in excellent yields up to 94% under mild reaction conditions.     

Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols under ligand-, base-, and additive-free reaction conditions

An effective, convenient, and mild coupling reaction of benzylic alcohols with terminal alkynes has been developed. As an effective Lewis acid, Cu(OTf)₂-catalyzed arylmethylation of terminal alkynes with benzylic alcohols generated the corresponding products in BrCH₂CH₂Br with good yields in the absence of ligand, base, and additive.     

Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols

The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]⁺[MeO‐B₂pin₂]^? favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C.     

Ruthenium Trichloride-Catalyzed Allyl Ether Formation

Ruthenium complexes are well known to catalyze the oxidation of alcohols,¹ where a ruthenium alkoxide has been assumed as a key intermediate. The formation of symmetrical ethers from certain carbinols is also catalyzed by ruthenium in a similar manner.² We now wish to report that the mixed etherification of allyl alcohols is catalyzed by RuCl₃, which acts as a Lewis acid to cleave the allylic carbon—oxygen bond.     

Carbohydrate Phosphorylation with Phosphoric Acid,Polyphosphoric Acid,Pyrophosphoric Acid,and Anhydrous Phosphoric Acid

Abstract

Pyrophosphoric acid was first reported as a phosphorylating agent for highmolecular weight alcohols in 1934¹. Direct phosphorylating of sugars and sugar derivatives was first carried out by Cherbuliez² who used polyphosphoric acid on alcohols, amines and glycols. These precedents suggested to Seegmiller and Horecker in 1951³ to try tetraphosphoric (polyphosphoric) acid, as supplied by commercs, as the phosphorylating agent of carbohydrate phosphorylation. Carbohydrates can be phosphorylated when all but one of the positions is blocked by suitable protective groups, or, on rare occasions, in the unblocked, “natural” stata.? The latter method can be used only on terminal, C₅ or C₆ positions as the 5-phosphates of pentoses and the 6-phosphates of hexoses are more stable at low pH than other phosphates and can withstand an acidic hydrolysis of the mixture of phosphorylated sugars resulting from such phosphorylation. For the phosphorylation of easily available, cheap pentoses and hexoses in the 5- and 6-positions respectively, with cheap polyphosphoric acid, this is the method of choice.     

Stereo- and regiocontrol of acyclic systems via the lewis acid mediated reaction of allylic stannanes with aldehydes

The reaction of crotyltrialkylstannanes (1) with aldehydes in the presence of BF₃,OEt₂, produces the corresponding erythro homoallyl alcohols (2) predominantly regardless of the geometry of the double bond. Further, the Lewis acid mediated reaction exhibits the enhanced Cram selectivity in comparison with other allylic organometallic reactions which proceed in the absence of Lewis acids. Use of AlCl₃-i-PrOH as the Lewis acid entirely changes the reaction course; the linear adduct (12) is produced rather than the branched adduct (13). The reaction of 1-BF₃,OEt₂ system is applied to the short and stereoselective synthesis of the (±) Prelog-Djerassi lactonic acid (16) and (-) verrucarinolactone (19).     

Synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-thiaspiro[5.5]undecanes from exo-glycal

A new spirocyclization was developed for the synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-thiaspiro[5.5]undecanes by reaction of exo-glycal with aryl alcohols or thiophenols in the presence of Lewis acid BF₃·OEt₂. The reaction proceeded through tandem Ferrier rearrangement, glycosylation, and Friedel–Crafts alkylation to provide the corresponding products in good to excellent yields.     

Ultrasound-assisted addition of alcohols to N-acyliminium ions mediated by In(OTf)3 and synthesis of 1,2,3-triazoles

An easy and mild approach using ultrasound-assisted reaction addition of alcohols to N-acyliminium ion mediated by Lewis acid, In(OTf)₃, allowed the synthesis of ether pyrrolidinones; next, the products were converted to 1,2,3-triazoles using click chemistry reaction conditions. The products in both reactions were afforded in moderate to good yields.     

A Janus‐Headed Lewis Superacid: Simple Access to,and First Application of Me3Si‐F‐Al(ORF)3

Upon reaction of gaseous Me₃SiF with the in situ prepared Lewis acid Al(OR^F)₃, the stable ion‐like silylium compound Me₃Si‐F‐Al(OR^F)₃ 1 forms. The Janus‐headed 1 is a readily available smart Lewis acid that differentiates between hard and soft nucleophiles, but also polymerizes isobutene effectively. Thus, in reactions of 1 with soft nucleophiles (Nu), such as phosphanes, the silylium side interacts in an orbital‐controlled manner, with formation of [Me₃Si?Nu]⁺ and the weakly coordinating [F?Al(OR^F)₃]^– or [(^FRO)₃Al‐F‐Al(OR^F)₃]^– anions. If exchanged for hard nucleophiles, such as primary alcohols, the aluminum side reacts in a charge‐controlled manner, with release of FSiMe₃ gas and formation of the adduct R(H)O?Al(OR^F)₃. Compound 1 very effectively initiates polymerization of 8 to 21 mL of liquid C₄H₈ in 50 mL of CH₂Cl₂ already at temperatures between ?57 and ?30 °C with initiator loads as low as 10 mg in a few seconds with 100 % yield but broad polydispersities.     

Use of CaH2 as a reductive hydride source: reduction of ketones and imines with CaH2/ZnX2 in the presence of a Lewis acid

A new combination reagent of CaH₂/ZnX₂ effectively reduced a variety of ketones and imines to the corresponding alcohols and amines, respectively, in the presence of a catalytic amount of a Lewis acid such as Ti(O-i-Pr)₄, Al(O-i-Pr)₃, B(O-i-Pr)₃ and ZnF₂.     

A general method for the synthesis of enantiopure aliphatic chain alcohols with established absolute configurations. Part 2, via catalytic reduction of acetylene alcohol MαNP esters

A general method for synthesizing enantiopure (100% ee) aliphatic alcohols with established absolute configurations has been developed and applied to alcohols CH₃(CH₂)_n–CH(OH)–(CH₂)_mCH₃, the enantiomeric discrimination of which is the most difficult, if m = n + 1 and n is large. Racemic saturated alcohols with short chains could be directly enantioresolved as (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid) esters by HPLC on silica gel, and their absolute configurations were simultaneously determined by ¹H NMR diamagnetic anisotropy. However, the application of this powerful MαNP ester method to alcohols with long chains was difficult, because of smaller values of the separation factor α. In such cases, the use of the corresponding acetylene alcohol MαNP esters was crucial. Acetylene alcohol MαNP esters were largely separated by HPLC on silica gel, and their absolute configurations were unambiguously determined by ¹H NMR as reported in the Part 1 paper. The MαNP esters obtained with established absolute configurations were catalytically hydrogenated to yield saturated alcohol MαNP esters. It was evidenced that no racemization occurred at the stereogenic center of the alcohol moiety during catalytic hydrogenation, by the coinjection of MαNP esters in HPLC. From the MαNP esters obtained, enantiopure (100% ee) aliphatic chain alcohols with established absolute configurations were recovered. Although the [α]_D values of these alcohols were too small for the identification of the enantiomers, it was clarified that the analytical HPLC of MαNP esters is useful for identification in most cases.     

Metal/linked-BINOL complexes: Applications in direct catalytic asymmetric Mannich-type reactions

Development of metal/linked-BINOL complexes and their applications in direct catalytic asymmetric Mannich-type reactions of hydroxyketones are reviewed. A Et₂Zn/linked-BINOL complex was effective for diastereo- and enantioselective synthesis of β-amino alcohols. By choosing the proper protective groups on the imine nitrogen, either anti- or syn-β-amino alcohol was obtained in excellent enantioselectivity (up to >99.5% ee) using the same zinc catalysis. Y{N(SiMe₃)₂}₃/linked-BINOL complex was effective for various hydroxyketones, affording syn-β-amino alcohols with high enantioselectivity (up to 98% ee). To broaden the nucleophile scope to carboxylic acid derivatives, N-acylpyrrole was utilized as an ester equivalent donor. In(O-iPr)₃/linked-BINOL complex was effective for generating an In-enolate from N-acylpyrrole in situ, giving Mannich adducts with high enantioselectivity (up to 98% ee).     

A chiral iron(II)-pybox catalyst stable in aqueous media. Asymmetric Mukaiyama-aldol reaction

Among various transition metals, iron is nontoxic, cheap and hence of great potential synthetic use. We report herein a water stable chiral Lewis acid containing an iron(II) ion and a pybox-type ligand. The resulting cationic aqua complex of C₂-symmetry is an effective Lewis acid catalyst for asymmetric Mukaiyama-aldol reactions in aqueous media. The aldol products have been obtained in good yields, syn-diastereoselectivities and ca. 70% levels of enantioselectivity.     

A new methodology of intramolecular hetero Diels-Alder reaction with β-alkoxy-substituted conjugated nitroalkenes as heterodienes: stereoselective one-pot synthesis of trans-fused bicyclic γ-lactones

Tandem reaction of (E)-1-ethoxy-2-nitroethylene with δ,ε-unsaturated alcohols leading to stereoselective trans-fused bicyclic γ-lactones has been developed using a catalytic amount of a Lewis acid such as Yb(OTf)₃ and Ni(ClO₄)₂·6H₂O. This process involves the stereoselective tandem transetherification-intramolecular hetero Diels-Alder reaction leading to bicyclic nitronates, and sequential transformation of the nitronate moiety to a lactone functional group under similar reaction conditions in good yields.     

Modification of catalysts for propylene polymerization: Alcohols and lewis bases

A series of compounds were examined as modifiers for the high activity supported catalyst TiCl₄/MgCl₂–AlEt₃ for isospecific propylene polymerization. The list included two aromatic acid esters, 21 various Lewis bases, and 12 alcohols. A convenient graphic method is described for comparing the performance of different modifiers by plotting experimental results in coordinates “relative activity-isotactic index” and a kinetic rationale for this evaluation is presented. Aromatic acid esters exhibit much better performance than the bulk of Lewis bases but some sterically demanding aromatic alcohols show behavior show similar to that of the esters.     

[Cd2(tren)2(dl-alaninato)](ClO4)3: an efficient water-compatible Lewis acid catalyst for chemo-, regio-, and diastereo-selective allylation of various aldehydes

The use of [Cd₂(tren)₂(dl-alaninato)](ClO₄)₃·H₂O (I) (tren = tris(2-aminoethyl)amine) as an efficient water-compatible Lewis acid catalyst for the allylation of aldehydes in aqueous media was described. The reaction proceeded smoothly to afford the corresponding homoallyl alcohols in up to 96% yield. Additionally, cinnamyltributylstannane was selected as the allylation reagent, the regio- and diastereoselectivity of the reaction favors the formation of the γ-product and the anti isomers, respectively.     

Lewis-acid catalyzed formation of dihydropyrans

A methodology is described for the synthesis of 2,6-disubstituted dihydro[2H]pyrans through a Lewis-acid catalyzed 6-endo-trig cyclization of β-hydroxy-γ,δ-unsaturated alcohols. Employing alkyl-substituted allylic diols and catalytic amounts of a Lewis acid, such as BF₃·OEt₂, the corresponding syn-pyrans are formed highly diastereoselectively and in good yields. The described process is simple to execute, proceeds readily at ambient temperature, and is scalable.     

Lewis Acids as Activators in CBS‐Catalysed Diels–Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4

The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While ²H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT‐IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ(²H) values and rate constants k_DA, which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid–CBS complexes. Unexpectedly, a significant deviation was found for SnCl₄ as Lewis acid. The SnCl₄–CBS adduct was much more reactive than the Δδ(²H) values predicted and gave similar reaction rates to those observed for the prominent AlBr₃–CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid–CBS–naphthoquinone adducts and k_DA could be found. For the SnCl₄–CBS–naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA‐NOCV) calculations revealed the relevant interactions and activation mode of SnCl₄ as Lewis acid in Diels–Alder reactions.     

Synergistic Brønsted/Lewis acid catalyzed aromatic alkylation with unactivated tertiary alcohols or di-tert-butylperoxide to synthesize quaternary carbon centers

Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert-butylation of electron-rich arenes using di-tert-butylperoxide. This transformation inspired the development of a synergistic Brønsted/Lewis acid catalyzed aromatic alkylation that fills a gap in the Friedel–Crafts reaction literature by employing unactivated tertiary alcohols as alkylating agents, leading to new quaternary carbon centers. Corroborated by DFT calculations, the Lewis acid serves a role in enhancing the acidity of the Brønsted acid. The use of non-allylic, non-benzylic, and non-propargylic tertiary alcohols represents an underexplored area in Friedel–Crafts reactivity.

Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert-alkylation of arenes using di-tert-butylperoxide and tertiary alcohols.     

SiCl4-catalyzed/PR3-mediated β-C(sp3)−H functionalization of nitrones to α,β-unsaturated imines and aromatic heterocycles

A novel method of SiCl₄-catalyzed/PR₃-mediated β-C(sp³)?H functionalization of nitrones with aldehydes/ketones to α,β-unsaturated imines was developed. The synthesis of α,β-unsaturated imines mainly invovles deoxygenation and aldol condensation, each proceeding under a cooperation effect between Lewis acid and Lewis base. In addition, both the acidity and hydrolytic stability of the weak SiCl₄ were supposed to be enhanced by coordination with phosphine oxide (R?=?Et) or phosphoric triamide (R?=?NMe₂) that originated from deoxygenation of nitrones by PR₃. In the case of 6-membered nitrone, a [1,3]-hydride shift within the resulted α,β-unsaturated imines renders the aromatization leading to 3,5-dialkylpyridines.