Regioselective Dihalohydration Reactions of Propargylic Alcohols: Gold‐Catalyzed and Noncatalyzed Reactions

The regioselective conversion of propargylic alcohols into previously unreported α,α‐diiodo‐β‐hydroxyketones was achieved by treatment with N‐iodosuccinimide in the presence of a gold catalyst. The corresponding α,α‐dichloro‐β‐hydroxyketones were obtained by treatment with trichloroisocyanuric acid in the absence of a catalyst. The latter reaction can be extended to other alkynols. These transformations can be used to prepare potentially useful halogenated building blocks. Preliminary mechanistic studies suggest that the reaction involves participation of the acetonitrile solvent in the formation of a 5‐halo‐1,3‐oxazine intermediate.     

syn-selective direct catalytic asymmetric Mannich-type reactions of hydroxyketones using Y{N(SiMe3)2}3/linked-BINOL complexes

[reaction, structure: see text] Chiral Y{N(SiMe3)2}3/linked-BINOL catalyst generated Y-enolate in situ from various hydroxyketones (R2 = aryl, heteroaryl). Beta-amino-alpha-hydroxy ketones (R1 = aryl, heteroaryl, alkenyl) were obtained syn-selectively (up to 96/4) in high ee (up to 98%) and good yield (up to 98% yield).     

Guerbet reaction of primary alcohols leading to beta-alkylated dimer alcohols catalyzed by iridium complexes

[IrCl(cod)]2 and [Cp*IrCl2]2 complexes catalyzed efficiently the Guerbet reaction of primary alcohols to beta-alkylated dimer alcohols in good yields. For instance, the reaction of 1-butanol in the presence of [Cp*IrCl2]2 (1 mol %), t-BuOK (40 mol %), and 1,7-octadiene (10 mol %) produced 2-ethyl-1-hexanol in 93% yield. Various primary alcohols undergo the Guerbet reaction under the influence of Ir complexes to give the corresponding dimer alcohols in good yields. This method provides an alternative direct route to beta-alkylated primary alcohols which are prepared by aldol condensation of aldehydes followed by hydrogenation.     

Direct beta-alkylation of secondary alcohols with primary alcohols catalyzed by a CpIr complex

A new catalytic system for beta-alkylation of secondary alcohols has been developed. In the presence of [CpIrCl(2)](2) (Cp = pentamethylcyclopentadienyl) catalyst and base, the reactions of various secondary alcohols with primary alcohols give beta-alkylated higher alcohols in good to excellent yields without any hydrogen acceptor or hydrogen donor. This reaction proceeds via successive hydrogen-transfer reactions and aldol condensation. [reaction: see text]     

Enantiocontrolled synthesis of trialkyl-substituted stereogenic carbons. A general route to cis-3,5-dialkyl gamma-lactones

[reaction: see text] Lewis acid treatment of tertiary Co2(CO)6-propargylic alcohols having a stereochemically defined benzyloxy group at the gamma-benzyl position yielded after cobalt demetalation sec-dialkyl bishomopropargylic alcohols in good yields. The reaction is highly stereoselective and predictable, providing pure stereoisomers. The use of benzyl-alpha,alpha'-d2 ethers permitted the stereoselective d-labeling of methines and methylenes. Very simple chemical manipulations provided a general methodology to obtain the enantiomers of 3,5-dialkyl-gamma-lactones.     

Selective catalytic oxidative carbonylation of amino alcohols to ureas

[reaction: see text] Amino alcohols undergo W(CO)(6)-catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.     

Synthesis and Synthetic Application of Phosphonoketene Dithioacetals. New Synthesis of Dithioallenes and (alpha-Dithiocarboxyvinyl)phosphonates

Phosphonoketene dithioacetals 3a-e were obtained in good yields by the reaction of ethyl phosphonoacetates 1a,b with 2-4 equiv of thiols 2a-c in the presence of an alkylaluminum dichloride or dialkylaluminum chlorides. Reaction of 2,2-dithio-1-phosphonovinyl anions with aldehydes afforded allylic alcohols 4-7, 11-18 in good to moderate yields. Treatment of the alcohols 4-6 with t-BuOK in THF led to symmetrical [2 + 2] cycloadducts 20-22 of 1,1-(ethylenedithio)allenes in moderate yields, while a similar reaction of the alcohols 11-13 produced a mixture of symmetrical and unsymmetrical [2 + 2] cycloadducts of 1,1-(trimethylenedithio)allenes,23a-25a and 23b-25b, in 55-94% yields. The alcohol 15 on a similar treatment gave 3-tert-butyl-1,1-bis(ethylthio)allene (26) in quantitative yield. The structures of 20 and 23b were determined by X-ray analysis. Treatment of the alcohols 15 and 18 with trifluoromethanesulfonic acid/n-Bu(4)NX (X = Br, I) or triphenylphosphine/CBr(4) in CH(2)Cl(2) afforded alpha-phosphonodithioacryclic acid esters 34 and 35 in 25-52% yields. The tandem Michael-Wittig reaction of 35 with sodium salt of 2-pyrrolecarbaldehyde in DMF gave ethyl 3-phenyl-3H-cyclopenta[a]pyrrole-2-dithiocarboxylate (36) in 25% yield.     

Synthesis and photochromism of novel phenylene-linked photochromic bispyrans

[reaction: see text] Phenylene-linked bisnaphthopyrans were synthesized in good yields via the one-pot reaction of bis-propargyl alcohols with naphthols. Temperature-dependent photochromism in 1,4-phenylene-linked bispyrans leads to up to 60 nm bathochromic shift between the colored species formed at room temperature and at -20 degrees C. Better fatigue resistance and higher colorability was observed in 1,4-phenylene-linked bis-[2H]-naphtho[1,2-b]pyrans by comparison to the 1,3-phenylene linked bis-[2H]-naphtho[1,2-b]pyrans.     

Efficient and Ecofriendly Route for the Solvent-Free Synthesis of 4-Alkoxy-5H-chromen[2,3-d]pyrimidines Using Phosphonic Acid Functionalized KIT-6 Confined Ionic Liquid as Recoverable Catalyst

Phosphonic acid functionalized KIT-6 confined ionic liquid (IL, 1-butyl-3-methylimidazolium tetrafluoroborate [BMIm][BF₄]) catalyzed the one-pot condensation reaction of iminochromenes and salicylaldehydes with different primary alcohols to achieve the corresponding 4-alkoxy-5H-chromen[2,3-d]pyrimidines under solvent-free conditions and in good yields. This efficient nanocatalyst can be recovered for at least five reaction runs without significant loss of either activity or confined IL.     

Lanthanide triflate-catalyzed preparation of beta,beta-difluorohomopropargyl alcohols in aqueous media. Application to the synthesis of 4,4-difluoroisochromans

An indium-mediated Barbier-type reaction of difluoropropargyl bromide with several aldehydes in aqueous media was enhanced by a catalytic amount of a lanthanide triflate (5 mol %). The reaction gave the corresponding beta,beta-difluorohomopropargyl alcohols with high regioselectivity. The [2 + 2 + 2] alkyne cyclotrimerization of beta,beta-difluorohomopropargyl alcohols with monosubstituted acetylenes produced 4,4-difluoroisochromans in good yields with moderate regioselectivity.     

Nickel-catalyzed homoallylation reaction of aldehydes with 1,3-dienes: stereochemical and mechanistic studies

[reaction: see text] Contrary to what was reported, the coupling reaction of nickel-catalyzed cyclic diene such as cyclohexadiene with carbonyl compounds in the presence of diethyl zinc afforded gamma,delta-alkenyl alcohols in good yields.     

An efficient direct alpha-alkylation of ketones with primary alcohols catalyzed by [Ir(cod)Cl]2/PPh3/KOH system without solvent

alpha-Alkylation of ketones was successfully achieved by the reaction of ketones with alcohols catalyzed by iridium complexes in the presence of a small amount of base. For example, 2-octanone was allowed to react with butanol under the influence of [Ir(cod)Cl]2/PPh3/KOH to give 6-dodecanone in good yield. The reaction was found to proceed by using a 1:1 mixture of ketone and alcohol without use of any solvent.     

Cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to alpha,beta-enones

We have developed a cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to alpha,beta-enones. The asymmetric variant of this reaction, a kinetic resolution of secondary propargylic alcohols, was also developed with good selectivity. The mechanistic study revealed that the isomerization proceeds through intramolecular 1,3- and 1,2-hydrogen migration pathways. [reaction: see text]     

A New Method of Deoxygenation in the Synthesis of Taxanes by Hypophosphorous Acid

Based on the chemistry involved in the radical chain deoxygenation of alcohols by the Barton-McCombie reaction, numerous applications in the synthesis of taxanes were reported. [1] In the original Barton-McCombie method,tributyltin hydride was the hydrogen atom source and tributyltin radical generated from the hydride served as a chain carrier. [2] Although the method gave the good yield and found many applications, the problems associated with the price, toxicity and removal of tin residues prompted search for other hydrogen atom sources. Radical chain deoxygenation of alcohols can be carried out with phosphorus centered radicals, generated from hypophosphorous acid orits salts. [3]     

Lewis acid-catalyzed ring-opening reactions of methylenecyclopropanes with alcoholic or acidic nucleophiles

[reaction: see text] Methylenecyclopropanes can react with various nucleophiles such as alcohols, phenols, carboxylic acids, and thiols to give the corresponding homoallylic esters or ethers in good yields with good stereoselectivities in the presence of Lewis acids.     

Sequential pericyclic reaction of ene-diallenes: an efficient approach to the steroid skeleton

[reaction: see text] The one-pot construction of polycyclic aromatic systems from acyclic ene-bis(propargyl alcohols) was achieved through a tandem dual [2,3]-sigmatropic rearrangement/6pi-electrocyclic reaction/intramolecular [4 + 2] cycloaddition sequence. A steroidal compound was conveniently synthesized using the present method.     

Rhodium-catalyzed allyl transfer from homoallyl alcohols to aldehydes via retro-allylation followed by isomerization into ketones

Retro-allylation of homoallyl alcohol by rhodium catalysis occurs to generate allylrhodium species. This allylrhodium reacts with aldehydes to give the corresponding secondary alcohols in situ. Isomerization of these alcohols proceeds in the same pots to furnish the corresponding saturated ketones in good yields. [reaction: see text]     

Efficient and stereoselective synthesis of allylic ethers and alcohols

[Structure: see text] A short and efficient synthesis of allylic TBS ethers and allylic alcohols has been developed, based upon a unique Kocienski-Julia olefination reaction. Allylic alcohols and allylic ethers are obtained in good to excellent yields and with high (E)-selectivity. The conditions are mild and the procedure is broadly applicable.     

Expedient protocol for solid-phase synthesis of secondary and tertiary amines

[reaction: see text] An expedient solid-phase synthetic approach to secondary and tertiary amines was developed. The protocol employs conversion of resin-bound amino alcohols to the corresponding iodides, followed by iodide displacement with primary or secondary amines or with unprotected amino alcohols. This two-step procedure, affording products in good to excellent yields, is suitable for solid-phase synthesis of polyamines.     

Synthesis and transformation of [difluoro(phenylseleno)methyl]- trimethylsilane

[reaction: see text] A novel and efficient strategy was developed to synthesize [difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF(2)TMS, 2), which was further utilized as a nucleophilic difluoromethylating reagent to incorporate the difluoro(phenylseleno)methyl (PhSeCF(2)) group into carbonyl compounds in good yields. The resulting PhSeCF(2)-containing alcohols 3 could be conveniently converted into corresponding difluoromethyl alcohols 4 by a radical deselenylation.