Emergence of 2,3,5-trisubstituted tetrahydrofuran natural products and their synthesis.

The emergence of various 2,3,5-trisubstituted tetrahydrofuran natural products in the recent literature and their synthesis is the focus of this review. These molecules exhibit varied bioactivities and have garnered the interest of several synthetic chemists owing to their efficient synthesis. A few of them have been synthesized and their absolute stereo structure has been confirmed for the first time. These will be appealing candidates in future synthetic investigations along with the untouched molecules. Thus, this compilation will reveal these molecules for expansion of their diversity within the realm of both synthesis and bioactivity studies.

Synthesis of quinazoline-3-oxides via a Pd(ii) catalyzed azide-isocyanide coupling/cyclocondensation reaction.

A novel and efficient protocol concerning palladium catalyzing the three-component reaction of 2-azidobenzaldehyde, isocyanide, and hydroxylamine hydrochloride is developed. This method allows the rapid elaboration of quinazoline 3-oxides in a one-pot fashion. The 3-CR mainly involves concatenation of azide-isocyanide denitrogenative coupling, condensation with hydroxylamine and 6-exo-dig cyclization. The salient features of the methodology are operational simplicity, use of milder reaction conditions, being devoid of any additives such as oxidants (redox neutral) or base, and releasing N2 and H2O as the byproducts.

Sequential Pd(0)/Fe(III) Catalyzed Azide-Isocyanide Coupling/Cyclization Reaction: One-Pot Synthesis of Aminotetrazoles.

A rapid and efficient synthesis of aminotetrazole from aryl azides, isocyanides, and TMSN3 is developed. The reaction is promoted by sequential Pd(0)/Fe(III) catalysis. The reaction sequence utilizes the Pd-catalyzed azide-isocyanide denitrogenative coupling reaction to generate unsymmetric carbodiimide in situ, which reacts with TMSN3 in the presence of FeCl3 in a single pot. The methodology has distinct advantages over traditional synthetic approaches where toxic Hg and Pb salts are employed at stoichiometric scale.

Iodine-catalyzed cross-coupling of isocyanides and thiols for the synthesis of S-thiocarbamates.

A novel and efficient metal free, redox-neutral method for the synthesis of secondary thiocarbamates by cross-coupling of readily available thiophenol and isocyanides has been developed. The present methodology exhibits a broad substrate scope with good to excellent yields without an additive/extra oxidant under mild reaction conditions catalyzed by inexpensive iodine as the catalyst.

Asymmetric total synthesis of (+)-dihydroitomanallene B and formal synthesis of (-)-kumausallene.

The first asymmetric total synthesis of (+)-dihydroitomanallene B and its two diastereomers, and the formal synthesis of (-)-kumausallene are reported. The synthesis of the former was completed in 18 steps from 1,4-butanediol (3.4% overall yield), with diastereoselective Tsuji-Trost cyclization to access cis-2,5-disubstituted-3-oxygenated THF scaffold and a Corey-White-Posner reaction to install the bromoallene moiety as the key steps. In addition, the enantioselective formal total synthesis of (-)-kumausallene involving the key Tsuji-Trost cyclization is also realized.

Advances in Total Synthesis of Some 2,3,5-Trisubstituted Tetrahydrofuran Natural Products.

2,3,5-Trisubstituted tetrahydrofuran moiety is ubiquitous in natural products. These have served as appealing candidates for total synthesis due to their varied bio- and pharmaceutical activities. This tutorial review delineates the ingenious efforts by many researchers in the total synthesis of selected natural products based on a common 2,3,5-trisubstituted tetrahydrofuran core structure. Many of the syntheses display nuanced interplay between new methods and the ingenuity of planned strategies achieved through catalysis or cascade chemistry. In some cases, the chiron approach has come quite handy, wherein the structural features and the stereochemistry in select molecules could map well with naturally available starting materials. This compilation also aims to enhance the diversity space based on these natural products and further interest in sustainable total synthesis.

Relay tricyclic Pd(ii)/Ag(i) catalysis: design of a four-component reaction driven by nitrene-transfer on isocyanide yields inhibitors of EGFR.

Synthesis of pyrazolo[1,5-c]quinazolines from four easily available precursors is presented through a one-pot tricyclic Pd(ii)/Ag(i) relay catalysis. The bimetallic relay cascade forges five new chemical bonds by concatenating six discrete chemical steps. The relay catalysis enables four-component assembly of pyrazolo[1,5-c]quinazolines that selectively inhibit EGFR, exhibit apoptosis through the ROS-induced mitochondrial-mediated pathway, and arrest the cell cycle at the G1 phase.

Ruthenium Catalyzed Intramolecular C-S Coupling Reactions: Synthetic Scope and Mechanistic Insight.

A ruthenium catalyzed intramolecular C-S coupling reaction of N-arylthioureas for the synthesis of 2-aminobenzothiazoles has been developed. Kinetic, isotope labeling, and computational studies reveal the involvement of an electrophilic ruthenation pathway instead of a direct C-H activation. Stereoelectronic effect of meta-substituents on the N-arylthiourea dictates the final regioselective outcome of the reaction.