Diversity-Oriented Synthesis of Highly Functionalized Alicycles across Dipolar Cycloaddition/Metathesis Reaction

This Account gives an insight into the selective functionalization of some readily available commercial cyclodienes across simple chemical transformations into functionalized small-molecular scaffolds. The syntheses involved selective cycloadditions, followed by ring-opening metathesis (ROM) of the resulting azetidin-2-one derivatives or isoxazoline frameworks and selective cross metathesis (CM) by discrimination of the C=C bonds on the alkenylated heterocycles. The CM protocols have been described when investigated under various conditions with the purpose on exploring chemodifferentiation of the olefin bonds and a study on the access of the corresponding functionalized β-lactam or isoxazoline derivatives is presented. Due to the expanding importance of organofluorine chemistry in drug research as well as of the high biological potential of β-lactam derivatives several illustrative examples to the access of some fluorine-containing molecular entities is also presented in this synopsis.1 Introduction2 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Chlorosulfonyl Isocyanate Cycloaddition3 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Nitrile Oxide Cycloaddition4 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Metathesis5 Functionalization of sSome Cyclodienes across Nitrile Oxide Cycloaddition6 Selective Synthesis of Functionalized Alicycles across Ring-Opening Metathesis7 Selective Synthesis of Functionalized Alicycles through Cross Metathesis8 Summary and Outlook9 List of Abbreviations

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.

One-Pot Synthesis of Oxazolidinones and Five-Membered Cyclic Carbonates from Epoxides and Chlorosulfonyl isocyanate: Theoretical Evidence for the Asynchronous Concerted Pathway

The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having substituted phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained with a ratio close to (1:1) in the cyclization reactions. The best reaction conversion for the synthesis of these compounds was carried out in dichloromethane (DCM). The method presented here has distinct advantageous over the existing methods such as one-pot reaction, shorter reaction times, metal-free reagent, good yields and very simple purification method. The mechanism for the cycloaddition reactions has been elucidated using density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level. The investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates revealed that the cycloaddition reaction takes place through an asynchronous concerted mechanism in gas phase and in DCM.

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

In this study, we developed a new addition reaction of chlorosulfonyl isocyanate (CSI), starting from 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione. The addition reaction of CSI with 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione resulted in the formation of ylidenesulfamoyl chloride, whose exact configuration was determined by X-ray crystal analysis. We explain the mechanism of product formation supported by theoretical calculations.

Studies on the synthesis and properties of 1,1,1-trinitroprop-2-yl urea, carbamate and nitrocarbamate

Potential high energetic dense oxidizers with the 1,1,1-trinitropropan-2-yl moiety are described in this study. The urea, N,N′-bis(1,1,1-trinitropropan-2-yl)urea (1), is synthesized by the reaction of urea with acetaldehyde and trinitromethane. The reaction of 1,1,1-trinitropropan-2-ol (2) with the reagent chlorosulfonyl isocyanate results in the formation of 1,1,1-trinitroprop-2-yl carbamate (3). The nitration of 3 with anhydrous nitric and sulfuric acid yields the nitrocarbamate (4). All compounds were fully characterized by multinuclear NMR (1H, 13C, 14/15N) and vibrational spectroscopy, mass spectrometry and elemental analysis (C,H,N). For analysis of the thermostability differential scanning calorimetry (DSC) was used. Energetic properties, the sensitivities towards impact, friction and electrostatic discharge were tested and compared with the corresponding 2,2,2-trinitroethyl and 3,3,3-trinitropropyl derivatives. The crystal structures of two compounds with that of the 1,1,1-trinitroprop-2-yl moiety have been determined by low temperature X-ray diffraction and discussed. The energies of formation were evaluated and several detonation parameters such as the velocity of detonation and the propulsion performance were calculated with the program package explo5.

Synthesis of an Oxacepham derivative from 1,2-O-Cyclohexylidene-α-DXylofuranose

Carbohydrates have gained much attention as cheap chiral starting materials in stereocontrolled target oriented synthesis. β-lactam antibiotics still remain the main tool against bacterial infections but the search for new active compounds has not been the aim of reported investigations. Synthesis of β-lactam antibiotics from carbohydrate precursors played a special role owing to the importance of these classes of compounds in modern chemotherapy. In this report, we carried out this subject to synthesize β-lactam derivative (oxacepham) via [2 + 2] cycloaddition of chlorosulfonyl isocyanate (CSI) to vinyl ether derived from carbohydrate (α-D-glucose).