Concise Synthesis of α‐Methylene‐β‐hydroxy‐γ‐carboxy‐γ‐lactams

A concise protocol for the synthesis of α‐methylene‐β‐hydroxy‐γ‐carboxy‐γ‐lactams has been described via alkylation of amino acid derived iminoesters with α‐bromomethylmethacrylate, followed by allylic hydroxylation. All the synthesized compounds have been evaluated for their cytotoxicity on multiple myeloma cancer cell lines.     

Synthesis of γγγ-trifluorocarbonyl compounds

γγγ-Trifluorocarbonyl compounds are easily obtained in a good yield by introduction of the 1,1,1-trifluoroethyl moiety (CF₃-CH₂-) on the -methylene group of a ketone.     

Efficient Synthesis of α‐Benzylidene‐γ‐methyl‐γ‐butyrolactones

A concise synthesis of α‐benzylidene‐γ‐methyl‐γ‐butyrolactones 5a – g from substituted benzaldehydes is described. Compounds 1a – g on reaction with phosphorane 2 , provide the pentenoates 3a – g , which can be hydrolyzed to the acids 4a – g . The latter are cyclized to the corresponding butyrolactones 5a – g in excellent yields. The pentenoates 3a – g , on acid catalyzed cyclization, also provide 5a – g in very high yields.     

A Novel Synthesis of γ,δ‐Unsaturated Aldehydes from α‐Formyl‐γ‐lactones

A preparatively useful one‐step transformation of γ,γ‐disubstituted α‐formyl‐γ‐lactones into trisubstituted γ,δ‐unsaturated aldehydes is described, by means of catalytic amounts of either AcOH or AcOEt in the vapor phase over a glass support. A mechanistic rationale is proposed.     

Rhodium‐Catalyzed Asymmetric Arylation of β,γ‐Unsaturated α‐Ketoamides for the Construction of Nonracemic γ,γ‐Diarylcarbonyl Compounds

A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide.     

Base‐Catalyzed Highly Stereoselective Conversion of γ‐Hydroxy‐α,β‐acetylenic Esters to γ‐Acetoxy Dienoates

A convenient route with high stereo control to γ‐acetoxy dienoates is provided by the reaction of methyl propiolate with aldehydes in the presence of ZnEt₂ and N‐methylimidazole at room temperature, followed by the catalytic conversion of the resulting γ‐hydroxy‐α,β‐acetylenic esters with p‐N,N‐dimethylaminopyridine (DMAP) in acetic anhydride (see scheme).

     

γ,δ‐ and δ,ε‐Unsaturated Aldehydes from γ‐ and δ‐Lactones in One Step. Preliminary Communication

A one‐step transformation of γ‐ and δ‐(spiro)lactones into γ,δ‐ and δ,ε‐unsaturated aldehydes with an excess of formic acid in the vapor phase over a supported manganese catalyst is described for the first time. The scope and limitations of this new reaction are shown with different lactones as substrate, and a mechanistic rationale is proposed.     

Radical‐initiated polymerization of β‐methyl‐α‐methylene‐γ‐butyrolactone

β‐Methyl‐α‐methylene‐γ‐butyrolactone (MMBL) was synthesized and then was polymerized in an N,N‐dimethylformamide (DMF) solution with 2,2‐azobisisobutyronitrile (AIBN) initiation. The homopolymer of MMBL was soluble in DMF and acetonitrile. MMBL was homopolymerized without competing depolymerization from 50 to 70 °C. The rate of polymerization (R_p) for MMBL followed the kinetic expression R_p = [AIBN]^0.54[MMBL]^1.04. The overall activation energy was calculated to be 86.9 kJ/mol, k_p/k_t^1/2 was equal to 0.050 (where k_p is the rate constant for propagation and k_t is the rate constant for termination), and the rate of initiation was 2.17 × 10^?8 mol L^?1 s^?1. The free energy of activation, the activation enthalpy, and the activation entropy were 106.0, 84.1, and 0.0658 kJ mol^?1, respectively, for homopolymerization. The initiation efficiency was approximately 1. Styrene and MMBL were copolymerized in DMF solutions at 60 °C with AIBN as the initiator. The reactivity ratios (r₁ = 0.22 and r₂ = 0.73) for this copolymerization were calculated with the Kelen–Tudos method. The general reactivity parameter Q and the polarity parameter e for MMBL were calculated to be 1.54 and 0.55, respectively. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1759–1777, 2003     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.     

Two‐Step Synthesis of Multifunctional γ‐Lactams from γ‐Lactone

We present herein an efficient and rapid method for the synthesis of N,1‐dialkyl‐4‐(2‐hydroxyethyl)‐5‐oxopyrrolidine‐3‐carboxamides based on the conversion of γ‐lactone to γ‐lactam via the conjugate addition of primary amines to an ethyl α‐functionalized acrylate followed by intramolecular cyclization.     

PPh3⋅HBr‐DMSO Mediated Expedient Synthesis of γ‐Substituted β,γ‐Unsaturated α‐Ketomethylthioesters and α‐Bromo Enals: Application to the Synthesis of 2‐Methylsulfanyl‐3(2 H)‐furanones

An efficient chemoselective general procedure for the synthesis of γ‐substituted β,γ‐unsaturated α‐ketomethylthioesters from α,β‐unsaturated ketones has been achieved through an unprecedented PPh₃?HBr‐DMSO mediated oxidative bromination and Kornblum oxidation sequence. The newly developed reagent system serves admirably for the synthesis of α‐bromoenals from enals. Furthermore, AuCl₃‐catalyzed efficient access to 3(2H)‐furanones from the above intermediates under extremely mild conditions are described.     

Matrix-isolated NCl. Radiative rates for b Π→a Δ, b Σ→X Σ and a Δ→X Σ in solid argon

Radiative rates for the b→a, b→X, and a→X transitions in NCl have been determined in solid argon. The rates - corrected for the refractive index - are 520, 260, and 0.27 s⁻¹. The b→X and a→X rates are in good agreement with calculated rates, whereas the b→a rate is enhanced by five orders of magnitude in the matrix.     

Organocatalytic Enantioselective Synthesis of Tetrasubstituted α‐Amino Allenoates by Dearomative γ‐Addition of 2,3‐Disubstituted Indoles to β,γ‐Alkynyl‐α‐imino Esters

The first asymmetric synthesis of tetrasubstituted α‐amino allenoates by a chiral phosphoric acid catalyzed dearomative γ‐addition reaction of 2,3‐disubstituted indoles to β,γ‐alkynyl‐α‐imino esters is reported. This method provides access to a series of highly functionalized tetrasubstituted allenes featuring quaternary stereocenters in high yields, and with excellent regio‐, diastereo‐, and enantioselectivities under mild conditions without by‐product formation. Representative large‐scale reactions and diverse transformations of the products into various scaffolds with potential biological activities render are also disclosed. The mechanism of the reaction was elucidated by control reactions and DFT calculations.     

Co‐crystals of 3‐deoxy‐3‐fluoro‐α‐d‐glucopyranose and 3‐deoxy‐3‐fluoro‐β‐d‐glucopyranose

3‐Deoxy‐3‐fluoro‐d ‐glucopyranose crystallizes from acetone to give a unit cell containing two crystallographically independent molecules. One of these molecules (at site A) is structurally homogeneous and corresponds to 3‐deoxy‐3‐fluoro‐β‐d ‐glucopyranose, C₆H₁₁FO₅, (I). The second molecule (at site B) is structurally heterogeneous and corresponds to a mixture of (I) and 3‐deoxy‐3‐fluoro‐α‐d ‐glucopyranose, (II); treatment of the diffraction data using partial‐occupancy oxygen at the anomeric center gave a high‐quality packing model with an occupancy ratio of 0.84:0.16 for (II):(I) at site B. The mixture of α‐ and β‐anomers at site B appears to be accommodated in the lattice because hydrogen‐bonding partners are present to hydrogen bond to the anomeric OH group in either an axial or equatorial orientation. Cremer–Pople analysis of (I) and (II) shows the pyranosyl ring of (II) to be slightly more distorted than that of (I) [θ_(I) = 3.85 (15)° and θ_(II) = 6.35 (16)°], but the general direction of distortion is similar in both structures [ϕ_(I) = 67 (2)° (B_C1,C4) and ϕ_(II) = 26.0 (15)° (^C3TB_C1); B = boat conformation and TB = twist‐boat conformation]. The exocyclic hydroxymethyl (–CH₂OH) conformation is gg (gauche–gauche) (H5 anti to O6) in both (I) and (II). Structural comparisons of (I) and (II) to related unsubstituted, deoxy and fluorine‐substituted monosaccharides show that the gluco ring can assume a wide range of distorted chair structures in the crystalline state depending on ring substitution patterns.