Electronically-controlled diastereoselective synthesis of spirocycles via [4 + 2] cycloaddition of 2-arylidene-1-indenones with benzyne.

A one-pot electronically controlled [4 + 2] cycloaddition reaction of in situ generated benzyne with 2-arylidene-1-indenone is unveiled to construct novel spirocyclic frameworks in a regio- and diastereoselective fashion. This protocol features operational simplicity, good functional group tolerance and avoids the use of metal catalysts and external additives. This methodology has extended the synthetic application of 2-arylidene-1-indenones enabling easy access to valuable 10'H-spiro[indene-2,9'-phenanthren]-1(3H)-ones in good yields.

Unusual Behavior of Ketoximes: Reagentless Photochemical Pathway to Alkynyl Sulfides.

The unique properties of ketoximes are used prominently for the synthesis of heterocycles. In contrast, their potential to absorb light and photoelectron transfer processes remains challenging. Widespread interest in controlling direct excitation of ketoxime tacticity unlocks unconventional reaction pathways, enabling photochemical intramolecular skeletal modification to constitute alkynyl sulfides that cannot be realized via traditional activation. Despite decades of advancements, the alkynyl sulfides, particularly those composed of polar functionalities and derived from renewable sources, remain unknown. These findings demonstrate the importance of decelerated ketoxime from ß-oxodithioester for the identification of reaction conditions. The method uses mild reaction conditions to generate excited-state photoreductant for the functionalization of an array of alkynyl sulfides. Additionally, a fundamental understanding of elementary steps using electrochemical and spectroscopic techniques/experiments revealed a PCET pathway to this transformation, while the involved substrates and their properties with improved economical tools indicated the translational potential of this method.

Visible-Light-Driven Photocatalyst- and Additive-Free Cross-Coupling of ß-Ketothioamides with α-Diazo 1,3-Diketones: Access to Highly Functionalized Thiazolines.

A photocatalyst- and additive-free, visible-light-mediated chemoselective domino protocol was devised to access fully substituted thiazoline derivatives from ß-ketothioamides and α-diazo 1,3-diketones at moderate temperature in open air. The reaction proceeds through in situ generation of electrophilic carbenes from α-diazo 1,3-diketones by a low-energy blue LED (448 nm), which undergoes selective coupling with nucleophilic ß-ketothioamides to give thiazolines by successive formation of C-S and C-N bonds in one stretch. Notably, the benign and clean conditions, operational simplicity, sustainability, 100 % carbon economy, high yields, and wide functional-group tolerance are further attributes of the strategy. A mechanistic rationale for this cascade reaction sequence is well supported by control experiments.

Visible-Light Photocatalysis of Eosin Y: HAT and Complementing MS-CPET Strategy to Trifluoromethylation of ß-Ketodithioesters with Langlois' Reagent.

A metal- and oxidant-free photoinduced strategy for thioxo sulfur-selective trifluoromethylation of ß-ketodithioesters at room temperature is reported. Excellent Z/E-stereoselectivity has been achieved with cheap and viable Langlois' reagent (CF3SO2Na, sodium triflinate) in the presence of eosin Y, which acts as a hydrogen atom transfer (HAT) catalyst. The reaction proceeds via disulfide intermediate disulfanediylbis(3-(alkylthio)-1-phenylprop-2-en-1-one) (a dimer of ß-ketodithioester) followed by complementing proton-coupled electron transfer-mediated reverse HAT cycle of eosin Y. This operationally simple and efficient protocol allows direct access to triflinated α-oxoketene dithioacetals in good to excellent yields bearing diverse synthetically useful functional groups of different electronic and steric nature.

Rhodium(II)-Catalyzed Annulative Coupling of ß-Ketothioamides with α-Diazo Compounds: Access to Highly Functionalized Thiazolidin-4-ones and Thiazolines.

An operationally simple and efficient one-pot protocol for the synthesis of highly functionalized thiazolidin-4-ones and thiazolines has been devised via Rh(OAc)2-catalyzed annulative coupling of ß-ketothioamides with diazo compounds under mild reaction conditions for the first time. This double functionalization of diazo compounds proceeds via selective S-alkylation followed by intramolecular N-cyclization enabling the formation of C-S and C-N bonds at moderate temperature. Notably, the products possess Z-stereochemistry with regard to the exocyclic C═C double bond at the 2-position of the ring. Further, the synthetic utility of the strategy has been revealed to access 2,3-dihydrobenzo[d]thiazoles. Remarkably, atom economy and tolerance of a wide range of functional groups are added characteristics to this strategy.

Phosphonium ylide catalysis: a divergent diastereoselective approach to synthesize cyclic ketene acetals [thia(zolidines/zinanes)] from ß-ketothioamides and dihaloalkanes.

Phosphonium ylides are being reported here as a catalyst for the formation of thiazolidines and 1,3-thiazinanes from ß-ketothioamides (which act as a three atom N, C, and S synthon) with dihaloalkanes via [3 + 2] and [3 + 3] annulations under metal-free conditions. An N,C,S-centred chemoselective dihaloalkane-controlled cascade process has been identified for the preparation of cyclic N,S-heterocycles (thiazolidines and 1,3-thiazinanes) from identical ß-ketothioamides. The reaction proceeds via consecutive sulfur and nitrogen nucleophilic attack of the thioamide on dihaloalkanes enabling the formation of S-C and N-C bonds. The ring size of the skeletally distinct N,S-heterocycles has been efficiently tuned by switching the use of 1,2- and 1,3-dihaloalkanes as α,ß- and α,γ-dielectrophiles. It is noteworthy that the products possess Z-stereochemistry with regard to the exocyclic C[double bond, length as m-dash]C double bond at the 2-position of the ring, revealing exclusive diastereoselectivity. Since phosphorus ylides have found limited use as catalysts, control experiments revealed their behaviour as a catalyst, which not only increase the catalyst tool box, but also would contribute to the field of ylide chemistry.

Access to Functionalized Thiazolothiadiazoles via the Chemoselective Cascade Heteroannulation of Thioamides with Hypervalent Iodine Reagents.

We describe herein a chemo- and regioselective cascade annulation between ß-ketothioamides and diazo-substituted hypervalent iodine reagents under transition-metal-free and base-free conditions at room temperature. Thus, a divergent construction of fused-heterocyclic scaffold thiazolothiadiazoles has been achieved with the advantages of operational simplicity, scalability, broad substrate compatibility, and mild reaction conditions. This one-pot strategy not only avoids potential toxicity but also broadens the arsenal of synthetic methods to obtain fused N,S-heterocyclic frameworks.

Base Mediated Diazirination via Iodine(III) Reagents.

Herein, we described an efficient method for the construction of highly functionalized diazirines from the carbohydrazide and diazo-substituted hypervalent iodine reagents. Unambiguous transformation has been designed with user applicable and easy practicable conditions. Remarkably, d-glucose, menthol, aspirin, proline, and lithocholic acid were efficiently diazirinated. Furthermore, the method is mild, robust, and highly selective, which successfully converted a variety of aryl, alkyl, benzyl, and heterocyclic hydrazides into the corresponding diazirine derivatives.

[2 + 3] Annulative Coupling of Tetrahydroisoquinolines with Aryliodonio diazo compounds To Access 1,2,4-Triazolo[3,4-a]isoquinolines.

Base promoted one-pot annulative coupling of 1,2,3,4-tetrahydroisoquinolines (THIQs) with hypervalent iodine(III) species aryliodonio diazo compounds has been devised for the direct construction of 1,2,4-triazolo[3,4-a]isoquinoline derivatives at room temperature in open air for the first time. This approach involves [2 + 3] cascade annulation of nucleophilic THIQ with an electrophilic aryliodonio diazo compound via N-H and α-C1(sp3)-H difunctionalization of THIQ.