Α-substituted Acroleins Research Articles

Boron Tribromide-Assisted Chiral Phosphoric Acid Catalysts for Enantioselective [2+2] Cycloaddition.

BBr3 -assisted chiral phosphoric acid catalysts for enantioselective [2+2] cycloaddition were developed. The reactions of phenyl vinyl sulfide with α-substituted acroleins proceeded, and the corresponding [2+2] cycloadducts were obtained with high enantioselectivity. In particular, the [2+2] cycloadduct obtained from methacrolein is a synthetically useful optically active cyclobutane, which could be transformed to a key intermediate for (+)-frontalin, a pheromone of Asian elephants.

Enantioselective chlorinative aldol reaction of α-substituted acroleins catalyzed by chiral phosphine oxides

The enantioselective chlorinative aldol reaction of α-substituted acroleins with aldehydes catalyzed by chiral phosphine oxides is described. A hypervalent silicon complex-derived chloride adds to the α-substituted acroleins to form the corresponding silyl enol ethers in situ, which subsequently reacts with aldehydes to produce the α-chloromethyl aldol adducts bearing a quaternary stereogenic center in good yields and stereoselectivities. When activated by a phosphine oxide catalyst, trichlorosilyl triflate acts as an effective promoter for the chlorinative aldol reaction as well as the chloride source; this discovery enabled the enantioselective chlorinative aldol reaction of α-substituted acroleins.

ChemInform Abstract: Palladium on Charcoal Catalyzed 3,4‐Hydroperoxidation of α‐Substituted Enals with Triethylsilane and Water.

Aldehyde α-hydroperoxides can be accessed from α-substituted acroleins with triethylsilane and water under Pd/C catalysis and aerobic conditions. The reaction is composed of a Pd/C-catalyzed conjugate reduction step and a hydroperoxidation step. The hydroperoxidation takes place via autoxidation of sufficiently stable enols formed in situ by transfer hydrogenation. Upon reduction, 2,2-disubstituted 1,2-diols are obtained directly from aldehydes.

Palladium on Charcoal Catalyzed 3,4-Hydroperoxidation of α-Substituted Enals with Triethylsilane and Water

Aldehyde α-hydroperoxides can be accessed from α-substituted acroleins with triethylsilane and water under Pd/C catalysis and aerobic conditions. The reaction is composed of a Pd/C-catalyzed conjugate reduction step and a hydroperoxidation step. The hydroperoxidation takes place via autoxidation of sufficiently stable enols formed in situ by transfer hydrogenation. Upon reduction, 2,2-disubstituted 1,2-diols are obtained directly from aldehydes.

Remote Tris(pentafluorophenyl)borane-Assisted Chiral Phosphoric Acid Catalysts for the Enantioselective Diels–Alder Reaction

Tris(pentafluorophenyl)borane-assisted chiral supramolecular phosphoric acid catalysts were developed for the model Diels–Alder reaction of α-substituted acroleins with cyclopentadiene. Two remotely coordinated tris(pentafluorophenyl)boranes should help to increase the Brønsted acidity of the active center in the supramolecular catalyst and create effective bulkiness for the chiral cavity. The prepared supramolecular catalysts acted as not only conjugated Brønsted acid–Brønsted base catalysts but also bifunctional Lewis acid–Brønsted base catalysts with the addition of a central achiral Lewis acid source such as catecholborane.

Boron Tribromide-Assisted Chiral Phosphoric Acid Catalyst for a Highly Enantioselective Diels-Alder Reaction of 1,2-Dihydropyridines.

BBr3-chiral phosphoric acid complexes are highly effective and practical Lewis acid-assisted Brønsted acid (LBA) catalysts for promoting the enantioselective Diels-Alder (DA) reaction of α-substituted acroleins and α-CF3 acrylate. In particular, the DA reaction of α-substituted acroleins with 1,2-dihydropyridines gave the corresponding optically active isoquinuclidines with high enantioselectivities. Moreover, transformations to the key intermediates of indole alkaloids, catharanthine and allocatharanthine, are demonstrated.

Chiral Primary‐Amine‐Catalyzed Conjugate Addition to α‐Substituted Vinyl Ketones/Aldehydes: Divergent Stereocontrol Modes on Enamine Protonation

Enantioselective protonation with a catalytic enamine intermediate represents a challenging, yet fundamentally important process for the synthesis of α-chiral carbonyls. We describe herein chiral primary-amine-catalyzed conjugate additions of indoles to both α-substituted acroleins and vinyl ketones. These reactions feature enamine protonation as the stereogenic step. A simple primary-tertiary vicinal diamine 1 with trifluoromethanesulfonic acid (TfOH) was found to enable both of the reactions of acroleins and vinyl ketones with good activity and high enantioselectivity. Detailed mechanistic studies reveal that these reactions are rate-limiting in iminium formation and they all involve a uniform H2 O/acid-bridged proton transfer in the stereogenic steps but divergent stereocontrol modes for the protonation stereoselectivity. For the reactions of α-branched acroleins, facial selections on H2 O-bridged protonation determine the enantioselectivity, which is enhanced by an OH⋅⋅⋅π interaction with indole as uncovered by DFT calculations. On the other hand, the stereoselectivity of the reactions with vinyl ketones is controlled according to the Curtin-Hammett principle in the CC bond-formation step, which precedes a highly stereospecific enamine protonation.

Oxazaborolidinium Ion-Catalyzed Cyclopropanation of α-Substituted Acroleins: Enantioselective Synthesis of Cyclopropanes Bearing Two Chiral Quaternary Centers

A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

Chiral Primary Amine Catalyzed Enantioselective Protonation via an Enamine Intermediate

Asymmetric Friedel—Crafts reaction of α-substituted acroleins with various indoles gives the desired products in high yields and enantioselectivities.

A Multicomponent Reaction between α-Substituted Acroleins, Nitroalkanes and Paraformaldehyde: Efficient Construction of Nitro δ-Lactol

A base-catalyzed multicomponent cascade reaction between α-substituted acroleins, nitroalkanes, and paraformaldehyde that proceeded smoothly to give high yields of functionalized δ-lactols under mild conditions, is described. This methodology is useful in the development of a concise synthetic route to natural products (±)-manzacidin A and C.

Asymmetric Epoxidation of α-Substituted Acroleins Catalyzed by Diphenylprolinol Silyl Ether

Asymmetric epoxidation of α-substituted acroleins with hydrogen peroxide has been catalyzed by diphenylprolinol diphenylmethylsilyl ether to afford α-substituted-β,β-unsubstituted-α,β-epoxy aldehyde with excellent enantioselectivity and the generation of a chiral quaternary carbon center. The method was applied to a short synthesis of (R)-methyl palmoxirate.

Construction of stereodefined 1,1,2,2-tetrasubstituted cyclopropanes by acid catalyzed reaction of aryldiazoacetates and α-substituted acroleins

Michael-initiated ring closure of aryldiazoacetates and alpha-substituted acroleins under acid catalysis offers a unique opportunity for the stereoselective formation of various tetrasubstituted cyclopropanes.

α-Methylenation of Aldehydes

A fast and chemoselective route to α-substituted acroleins is reported. Aqueous formaldehyde and several unfunctionalized as well as functionalized aldehydes 1 were used in an organocatalytic synthesis to give the α-methyl­enated products 2 in good to excellent yields (75-99%). Either pyrrolidine/propionic acid or the dipeptid Pro-β-Ala was used as the catalyst. The reactions were carried out in isopropanol at 45 °C for 1-25 hours. Already existing stereochemistry is not touched by these conditions and several protecting groups remain in the product. Also polymerization or crossed-adol products could not be observed. Other amine salts and amino acids were tested too, but were less active.

Enantioselective 1,3-Dipolar Cycloaddition Reaction between Diazoacetates and α-Substituted Acroleins: Total Synthesis of Manzacidin A

A titanium BINOLate catalyzed asymmetric 1,3-dipolar cycloaddition reaction between alpha-substituted acroleins and alkyl diazoacetates has been developed. With this methodology in hand, chiral 2-pyrazolines containing a quaternary stereogenic center were obtained in high to excellent enantioselectivities (up to 95% ee). The synthetic utility of the optically enriched 2-pyrazoline thus obtained was demonstrated in the short synthesis of manzacidin A.

Design of an Organocatalyst for the Enantioselective Diels—Alder Reaction with α‐Acyloxyacroleins.

We have realized the first enantioselective organocatalytic Diels−Alder reaction between α-substituted acroleins, such as α-acyloxyacroleins, and not only cyclic but also acyclic dienes. α-Acyloxyacroleins are useful as synthetic equivalents of α-haloacroleins. The present catalyst could be prepared in situ from pentafluorobenzenesulfonic acid (2.5−3.0 equiv) and chiral triamine (1 equiv) derived from H-l-Phe-l-Leu-N(CH2CH2)2. The enantioselective Diels−Alder reaction of 5-(benzyloxymethyl)cyclopentadiene, cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, and isoprene with α-(p-methoxybenzoyloxy)acrolein catalyzed by the above chiral ammonium salt (2.5−20 mol %) at −20−22 °C gave the corresponding adducts with 83, 83, 91, 92, and 88% ee, respectively.

Dibromomethane as One‐Carbon Source in Organic Synthesis: A Versatile Methodology to Prepare the Cyclic and Acyclic α‐Methylene or α‐Keto Acid Derivatives from the Corresponding Terminal Alkenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Dibromomethane as one-carbon source in organic synthesis: a versatile methodology to prepare the cyclic and acyclic α-methylene or α-keto acid derivatives from the corresponding terminal alkenes

Ozonolysis of mono-substituted alkenes A- 1 followed by reacting with a preheated mixture of CH 2Br 2–Et 2NH affords α-substituted acroleins A- 2 in good yields. Under very mild reaction conditions, these α-substituted acroleins A- 2 can be easily converted to α-methylene esters A- 4 , which could be further converted to the corresponding α-keto esters A- 5 . This methodology can be also applied to the preparation of α-methylene lactones B- 4 , α-methylene lactams, and α-keto lactones B- 5 with various ring sizes.

Cascade cycloaddition reactions involving dimethylhydrazones of α-substituted acroleins

Unusual cascade cycloaddition reactions with dimethylhydrazones of α-trimethylsilyloxyalkylacroleins acting as azadienes were found. Depending on the nature of the dienophile, the reactions give either fused heterocyclic compounds (when two consecutive Diels—Alder reactions take place) or azabicyclic compounds, resulting from the [2+4]- and [2+3]-cycloaddition cascade.

Preparation of α-substituted acroleins via the reaction of aldehyde or the corresponding ozonide with dihalomethane and diethylamine

Treatment of aldehydes or the corresponding ozonides with a mixture of dibromomethane and diethylamine afforded α-substituted acroleins in modest to good yields. The β-carbon of the acrolein ( nc, n = 1–16) derived from dibromomethane. Functional groups, such as ketone, hydroxy, acetoxy, bromide, iodide, ester are compatible with this reaction condition. The relative rates and yields of this transformation in dichloromethane were found to be in the following order: CH 2I 2 > CH 2Br 2 > CH 2Cl 2.

An efficient and versatile method for the preparation of α-keto acid derivatives from terminal alkenes

Ozonolysis of terminal alkenes followed by reacting with a preheated mixture of CH2Br2-Et2NH affords α-substituted acroleins, which can be converted to α-keto acid derivatives in three steps, under very mild reaction conditions.