Synthesis of New Thiazoles from α-Halohetaryl Ketones

Reactions of -bromoacetylphenoxathiin, -bromoacetylphenoxathiin 10,10-dioxide, or -bromoacetylthianthrene with certain p-(arylsulfonyl)thiobenzamides lead to the formation of the corresponding 2,4-disubstituted thiazoles. The new compounds were characterized through elemental analysis and spectral data (IR, ¹H NMR, and ¹³C NMR).     

Enantioselective Synthesis of Tertiary α-Hydroxyketones from Unfunctionalized Ketones: Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates

Aiming high: The title reaction for the synthesis of tertiary α-hydroxyketones is reported. Protected 1,2-enediol carbonates, the starting materials, were accessed from simple and readily available enol carbonates. Highly functionalized tertiary α-hydroxyketones can be obtained in high yield with excellent enantioselectivity using this method.     

A Catalytic Method for the Enantioselective Synthesis of α-Quaternary Ketones, α-Ketoesters and Aldehydes

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an α-quaternary stereocenter is described. Reactions utilize simple carboxylic acid or ester starting materials, a monodentate chiral phosphine, and afford a variety of aryl, alkenyl, alkynyl, and alkyl-substituted ketone and aldehyde products in 25–94 % yield and 90 : 10 to >99 : 1 enantiomeric ratio. Reactions proceed by acyl substitution with in situ formed chiral allylic nucleophiles, and display selectivity and conversion dependence on a protic additive. The utility of the approach is demonstrated through several product transformations.     

Enantioselective synthesis of α,α-disubstituted amines from nitroalkenes

Disubstituted nitroalkenes were converted into enantiomerically enriched amines (isolated as their hydrochloride salts) with enantiomeric excesses of 88 to >95% in three steps: (a) highly stereoselective conjugate addition of the potassium salt of 4-phenyloxazolidin-2-one; (b) radical-mediated removal of the nitro group; (c) cleavage of the oxazolidinone.     

Regiospecific Synthesis of α-Alkylated Ketones

Several solutions have been developed to avoid the troublesome di- and polyalkylation encountered in ketone enolate alkylations¹, including use of the covalent Li enolate, or “additives” to tighten the metal-oxygen bond (M = Si^2,3,4, Sn^5,6, Al⁶, B^7,8,9).     

Synthesis of α,β-Unsaturated Ketones via Enamines

Acylation of an enamine followed by acid hydrolysis constitutes the well-known Stork's reaction of synthesizing β-diketones.^1,2 This article reports that the acylated enamine 1 which corresponds to monoenamine of a β-diketone can be hydrogenated to a Mannich base 2 which on elimination by heating or treatment with acid yields the α, β-unsaturated ketone 3; further hydrogenation gives saturated ketone 4 in good yield (Scheme 1). A similar transformation effected by hydroboration has been reported by Montury and Góre.     

Catalytic Enantioselective Direct Aldol Addition of Aryl Ketones to α-Fluorinated Ketones

The catalytic enantioselective synthesis of α-fluorinated chiral tertiary alcohols from (hetero)aryl methyl ketones is described. The use of a bifunctional iminophosphorane (BIMP) superbase was found to facilitate direct aldol addition by providing the strong Brønsted basicity required for rapid aryl enolate formation. The new synthetic protocol is easy to perform and tolerates a broad range of functionalities and heterocycles with high enantioselectivity (up to >99:1 e.r.). Multi-gram scalability has been demonstrated along with catalyst recovery and recycling. ¹H NMR studies identified a 1400-fold rate enhancement under BIMP catalysis, compared to the prior state-of-the-art catalytic system. The utility of the aldol products has been highlighted with the synthesis of various enantioenriched building blocks and heterocycles, including 1,3-aminoalcohol, 1,3-diol, oxetane, and isoxazoline derivatives.     

Synthesis of novel chiral phosphines from α,α-trehalose

New disaccharide chiral phosphines, such as 4,6-O-benzylidene-2-(diphenylphosphino)-2-deoxy-α-d-altropyranosyl-(1,1)-4,6-O-benzylidene-2-(diphenylphosphino)-2-deoxy-α-d-altropyranoside 1 and 2-(diphenylphosphino)-2-deoxy-4,6-O-isopropylidene-α-d-altropyranosyl-(1,1)-2-(diphenylphosphino)-2-deoxy-4,6-O-isopropylidene-α-d-altropyranoside 9, were prepared from α,α-trehalose. We also succeeded in the synthesis of polyhydroxy chiral diphosphine 2-(diphenylphosphino)-2-deoxy-α-d-altropyranosyl-(1,1)-2-(diphenylphosphino)-2-deoxy-α-d-altropyranoside 5 by deprotection of isopropylidene groups.     

De Novo Design and Synthesis of Four-Helix Bundle Peptides

ＤｅＮｏｖｏＤｅｓｉｇｎａｎｄＳｙｎｔｈｅｓｉｓｏｆＦｏｕｒ－ＨｅｌｉｘＢｕｎｄｌｅＰｅｐｔｉｄｅｓＤｅＮｏｖｏＤｅｓｉｇｎａｎｄＳｙｎｔｈｅｓｉｓｏｆＦｏｕｒ－ＨｅｌｉｘＢｕｎｄｌｅＰｅｐｔｉｄｅｓ￥ＸｉａｎｇＱｕｎＬＩ；ＺｈｅｎＷｅｉＭＩＡＯ；Ｙ...     

Enantioselective Rhodium-Catalyzed Synthesis of α-Chloromethylene-γ-Butyrolactams from N-Allylic Alkynamides

The first enantioselective cycloisomerization with intramolecular halogen migration of various 1,6-enynes promoted by a cationic Rh-Synphos catalyst is reported. This method provides an efficient route to enantiomerically enriched γ-butyrolactam derivatives, which are important core scaffolds found in numerous natural products and biologically active molecules. Good yields and enantiomeric excesses up to 96% are achieved.     

Copper-Catalyzed Enantioselective Sonogashira Type Coupling of Alkynes with α-Bromoamides

An asymmetric copper-catalyzed Sonogashira type coupling between alkynes and α-bromoamides has been developed. This method represents a facile approach to synthetically useful β, γ-alkynyl amides from two readily available starting materials in a highly enantioselective manner. A Bisoxazoline diphenylanaline (BOPA) serves as the effective chiral ligand. Preliminary mechanistic studies support the formation of alkyl radical species .     

One‐Step Synthesis of Aromatic Terminal Alkynes from Their Corresponding Ketones under Microwave Irradiation

One‐step microwave‐assisted synthesis of phenylacetylenes 2a–j from the corresponding ketones 1a–j in the presence of a new reagent, PCl₅–pyridine, is described. The reaction is carried out under a simple operational and experimental procedure, avoiding the use of the complicated and harsh multistep reaction.     

Organocatalytic Enantioselective Acyloin Rearrangement of α-Hydroxy Acetals to α-Alkoxy Ketones

We report an unprecedented organocatalytic enantioselective acyloin rearrangement of α,α-disubstituted α-hydroxy acetals. In the presence of a catalytic amount of chiral binol-derived N-triflyl phosphoramide, α-hydroxy acetals rearranged to α-alkoxy ketones in good to high yields with high enantioselectivities. Formation of an ion pair between the in situ generated oxocarbenium ion and the chiral phosphoramide anion was proposed to be responsible for the highly efficient transfer of chirality. Conditions for removal of cyclohexyl and cyclopentyl groups from the corresponding α-alkoxy ketones were uncovered underpinning their potential general utility as hydroxy protecting groups. Conversion of the rearranged products to the enantioenriched α-hydroxy ketone, 1,2-diol, β-amino alcohol and 1,4-dioxane was also documented.     

New and Stereospecific Synthesis of α-Ethylenic Ketones

Abstract

H. Kise et al¹ have shown that the reaction of β-propiolactones 1 with ylides 2 give phosphonium carboxylate betaïne 3. We now report that, carried out under different conditions, reaction of lactones 1 with the same ylides proceeds through pathway (b). Thermolysis of 4 affords α-ethylenic ketones 5. The mecanism of this new extrusion reaction of triphenylphosphine oxyde probably involves the generation of an oxaphosphene as an intermediate.     

A Convenient Synthesis of β-Chloro, β-Methylthio α,β-Unsaturated Ketones from β-Oxodithioesters

The reaction of β-oxodithioesters with the Vilsmeier-Haack reagent prepared from POCl₃ and DMF provide β-chloro, β-methylthio α,β-unsaturated ketones in good yields.     

Synthesis of symmetrical acetylenic hydrocarbons and their α,ω-di-derivatives from α,α,α-trichloro- and α,α,α,ω-tetrachloro-alkanes

Summary By the action of sodium in xylene on polychloro hydrocarbons containing -CCl₂-CCl₂- or- CC1=CC1-, groupings the corresponding symmetrical acetylenic hydrocarbons containing 10,14, and 18 carbon atoms in the molecule were obtained. From ,-disubstituted tetrachloroalkanes by the same method 1,10-diethoxy-5-decyne, 1,14-diethoxy-7-tetradecyne, and 1,14-bisdiethylamino-7-tetradecyne were obtained.The spectra were determined in the Optical Laboratory of the Institute of Heteroorganic Compounds of the USSR by N. A. Chumaevskii, who we thank.     

One‐Pot Synthesis of α‐Formyloxy Ketones from Enolizable Ketones

One‐pot synthesis of α‐formyloxy tones as well as α‐acetoxy ketones from enolizable ketones and [hydroxy(tosyloxy) iodo] benzene (HTIB)/polymer supported [hydroxy(tosyloxy) iodo] benzene (PSHTIB) in N,N–dimethylformamide (DMF)/N, N–dimethylacetamide (DMA) in high yields is described.     

Hypervalent Iodine(III)-Catalysed Enantioselective α-Acetoxylation of Ketones

An enantioselective catalytic synthesis of α-acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide-based chiral iodoarene is reported. Catalyst turnover by in situ generation of the active iodine(III) derivative is achieved by oxidation with mCPBA in the presence of acetic acid. The prior transformation of ketones to easily accessible acetyl enol ethers is beneficial and yields up to 97 % with enantioselectivities up to 88 % ee are obtained using only low catalyst loadings of only 5 mol % under mild reaction conditions.     

Synthesis of α‐Hydroxy Ketones from Terpene Aldehydes

Abstract

Unsymmetrically substituted α‐hydroxy ketones possessing isoprenoid units within the molecule were synthesised from commercially available terpene aldehydes. The synthesis was applicable to α,β‐unsaturated aldehydes and afforded the respective α‐hydroxy‐methyl ketones in overall good yield. Tautomerisation of these products did not occur under the conditions of reaction but was observed upon heating. Diastereoisomeric α‐hydroxy ketones have been resolved, and X‐ray analysis on one of these analogues allowed for the elucidation of the stereochemistry after conversion into its camphanate ester.     

Synthesis of Enantiopure Dehydropiperidinones from α-Amino Acids and Alkynes via Azetidin-3-ones

Chiral dehydropiperidinones were synthesized in enantiopure form from α-amino acids and alkynes via azetidin-3-ones.