Synthesis of Alicyclic 2-Methylenethiazolo[2,3-b]quinazolinone Derivatives via Base-Promoted Cascade Reactions

The synthesis of alicyclic 2-methylenethiazolo[2,3-b]quinazo­l­inones is performed via base-promoted cascade reactions, starting from either alicyclic β-amino propargylamides using carbon disulfide, or from alicyclic ethyl 2-isothiocyanatocarboxylates by addition of propargylamine. In both cases the cascade reaction proceeds by way of a favoured 5-exo-dig process during the second ring closure, as confirmed by full NMR spectroscopic assignments. Moreover, a high-yielding retro­-Diels–Alder (RDA) reaction is performed on the norbornene derivatives leading to 2-methylene-2H-thiazolo[3,2-a]pyrimidin-5(3H)-ones. The obtained compounds exert modest antiproliferative activities against a panel of human gynaecological cancer cell lines.

Diversity-oriented functionalization of 2-pyridones and uracils

Heterocycles 2-pyridone and uracil are privileged pharmacophores. Diversity-oriented synthesis of their derivatives is in urgent need in medicinal chemistry. Herein, we report a palladium/norbornene cooperative catalysis enabled dual-functionalization of iodinated 2-pyridones and uracils. The success of this research depends on the use of two unique norbornene derivatives as the mediator. Readily available alkyl halides/tosylates and aryl bromides are utilized as ortho-alkylating and -arylating reagents, respectively. Widely accessible ipso-terminating reagents, including H/DCO2Na, boronic acid/ester, terminal alkene and alkyne are compatible with this protocol. Thus, a large number of valuable 2-pyridone derivatives, including deuterium/CD3-labeled 2-pyridones, bicyclic 2-pyridones, 2-pyridone-fenofibrate conjugate, axially chiral 2-pyridone (97% ee), as well as uracil and thymine derivatives, can be quickly prepared in a predictable manner (79 examples reported), which will be very useful in new drug discovery.

A Facile and Versatile Approach for the Synthesis of Degradable Polymers via Controlled Ring-Opening Metathesis Copolymerization

Norbornene derivatives (NBEs) are the most common monomers for ring-opening metathesis polymerization (ROMP) because they undergo living polymerization, yielding polymers with low dispersities and diverse functionalities. However, the all-carbon backbone of polyNBEs cannot be degraded. Polymer degradation is highly desired for many applications and has been a major limitation in ROMP chemistry. Here, we report a simple yet powerful method to synthesize controlled, degradable polymers by copolymerizing 2,3-dihydrofuran (DHF) with NBEs. DHF rapidly reacts with the Grubbs catalyst to form a thermodynamically stable Ru Fischer carbene, which is the only detectable active Ru species during the copolymerization, and the addition of NBEs becomes rate determining. This unique Ru Fischer carbene reactivity attenuates NBE homoaddition, which presented a significant challenge to previous copolymerization approaches, allows even incorporation of DHF units (acid-degradable enol ether bonds) throughout the copolymers, and thus enables complete polymer degradation while maintaining the favorable characteristics of living ROMP. We demonstrate the effective copolymerization of DHF with several types of NBEs to synthesize narrow-disperse polymers with tunable solubility, glass transition temperature, and mechanical properties. These polymers can all be fully degraded into small molecule or oligomeric species under mildly acidic conditions. This method can be readily adapted to traditional ROMP of widely used NBEs to synthesize new degradable polymers with tunable properties and facile degradation for various applications and environmental sustainability.

Synthesis of Polycycles and Oxacycles by Tandem Metathesis of endo–norbornene Derivatives

Here, we have demonstrated that the presence of a carbonyl group at C7 position is preventing the olefin metathesis of endo-norbornene derivatives due to the complexation of the metal alkylidene. Time-dependent NMR studies showed the presence of new proton signals in the metal alkylidene region, which indicate the formation of metal complex with the carbonyl group of the substrate. These observations were further proved by ESI-MS analysis. Whereas, computational studies provided that the catalyst was interacting with the C7 carbonyl group and aligned perpendicular to that of norbornene olefin. Later, these endo-keto norbornene derivatives were reduced to hydroxyl derivatives diastereoselectively. Ring-rearrangement metathesis (RRM) of these hydroxyl derivatives, produced the [6/5/6], and [5/6/5] carbo-tricyclic cores of the natural products in one step. Whereas the RRM of O-allyl derivatives, delivered the oxa-tricyclic compounds in a single step with excellent yields.

Highly photoluminescent poly(norbornene)s carrying platinum-acetylide complex moieties in the side chain: evaluation of oxygen sensing and TTA–UC

Ring-opening metathesis polymerization (ROMP) of norbornene derivatives is useful for preparing thermally stable and transparent polymeric materials with good moldability. This study deals with ROMP of norbornene monomer 1 bearing...

Cationic tungsten imido alkylidene N-heterocyclic carbene complexes for stereospecific ring-opening metathesis polymerization of norbornene derivatives

Cationic W alkylidene N-heterocyclic carbene complexes allow for the stereospecific ring-opening metathesis polymerization of norbornenes with high trans-iso- and high cis-syndiospecificity, respectively.