Regioselective Opening Research Articles

An alternative total synthesis of diplodialide-B

In this paper, an enantioselective synthesis of diplodialide-B has been described. To accomplish this target, a combination of regioselective ring opening of the chiral epoxide, Jacobsen hydrolytic kinetic resolution and Yamaguchi macrolactonization were used as the key steps.

TiCl4 catalyzed cleavage of (25R)-22-oxo-23-spiroketals. Synthesis of sapogenins with furostanol and pyranone E rings on the side chain

The regioselective opening of the F ring of 22-oxo-23-spiroketals 7a-d using TiCl4 in acetic anhydride yielded the novel furostanols 11a-d along with cholestanic derivatives 8a-d with pyranone E ring. The structures of the new derivatives thus obtained were established using one- (DEPT) and two-dimensional 1H, 13C NMR experiments (COSY, HSQC, HMBC, NOESY). The 22α-hydroxyl orientation in compounds 11a-d was proposed by comparison of the 13C chemical shifts with those of other aglycone members of this family, and confirmed by combined NOESY and X-ray diffraction analysis of compound 11a.

Molybdenum-catalyzed asymmetric anti-dihydroxylation of allylic alcohols

Asymmetric dihydroxylation of alkenes is one of the fundamental reactions in organic synthesis, but the anti-dihydroxylation is much less developed than its syn-variant. Here we report a highly enantio- and diastereoselective anti-dihydroxylation of allylic alcohols by using a chiral molybdenum-bishydroxamic acid complex as catalyst and environmentally benign hydrogen peroxide as oxidant. This reaction enables the construction of the 1,2,3-triol structural unit in high enantio- and diastereocontrol starting from simple allylic alcohol precursors. Our reaction complements the Sharpless dihydroxylation not only in its diastereoselectivity, but also in regiocontrol. The mechanistic studies indicate that this dihydroxylation reaction consists of an initial enantioselective epoxidation and the following in situ regioselective ring opening, both of which are promoted by the molybdenum-catalyst.

Enantioselective Synthesis of 3-Heterosubstituted-2-amino-1-ols by Sequential Metal-Free Diene Aziridination/Kinetic Resolution.

A general protocol for the enantioselective synthesis of 3-heterosubstituted-2-amino-1-ols was developed based on metal- free intramolecular regio- and stereoselective diene aziridination and regioselective opening. Kinetic resolution of the resulting (1'-NR1 R2 and 1'-SR)-4-oxazolidinones was performed using ABCs organocatalysts, expanding the application of this methodology.

Domino Synthesis of Thioflavones and Thioflavothiones by Regioselective Ring Opening of Donor-Acceptor Cyclopropane Using In-Situ-Generated Thiolate Anions.

A copper-catalyzed intramolecular ring opening of donor-acceptor cyclopropane is developed for the synthesis of 3-alkyl-carbonated thioflavones and further extended to 3-alkyl-carbonated thioflavothione, using xanthate as a sulfur surrogate. This reaction proceeds through thiolate formation/ring opening/Krapcho decarboxylation, followed by hydrogen abstraction, to give thioflavanone, which is further oxidized by in-situ-generated iodine from waste byproduct KI. Experimental studies prove that the charge-transfer complex is responsible for the conversion of thioketone to ketone.

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides.

Carba analogues of biologically relevant natural carbohydrates are promising structures for the development of future drugs endowed with enhanced hydrolytic stability. An open synthetic challenge in this field is the optimization of new methodologies for the stereo- and regioselective opening of α-gluco carbasugar 1,2-epoxides that allow for the preparation of pseudo mono- and disaccharides of great interest. Therefore, we investigated the effect of Lewis acids and solvate ionic liquids (SILs) on the epoxide ring opening of a model substrate. Of particular interest was the complete stereo- and regioselectivity, albeit limited to simple nucleophiles, toward the desired C(1) isomer that was observed using LiClO4. The results obtained with SILs were also remarkable. In particular, Li[NTf2]/tetraglyme ([Li(G4)]TFSI) was able to function as a Lewis acid and to direct the attack of the nucleophile preferentially at the pseudo anomeric position, even with a more complex and synthetically interesting nucleophile. The regioselectivity observed for LiClO4 and [Li(G4)]TFSI was tentatively ascribed to the formation of a bidentate chelating system, which changed the conformational equilibrium and ultimately permitted a trans-diaxial attack on C(1). To the best of our knowledge, we report here the first case in which SILs were successfully employed in a ring-opening process of epoxides.

Total synthesis of (±) aspidostomide B, C, regioisomeric N-methyl aspidostomide D and their derivatives

A full account of the total synthesis of aspidostomide B, C, their analogues and our synthetic efforts towards the synthesis of aspidostomide D, which led to the synthesis of regioisomeric N-methyl aspidostomide D, its analogues via epoxide opening strategy is presented. The synthesis of regioisomeric N-methyl aspidostomide D involves an efficient, five-step sequence, with 36.3% overall yield, starting from 3,4,5-tribromo-1H-pyrrole-2-carboxylic acid. The key features of this protocol are intramolecular cyclization, dehydration, oxidation, and a Lewis acid-mediated regioselective epoxide ring opening by C-3 position of 2,5-dibromo-1H-indole to furnish the title compounds.

Triphenylcarbenium Tetrafluoroborate as an Efficient Catalyst in the Regioselective Reductive Ring Opening of Benzylidene Acetals of Carbohydrates

AbstractTriphenylcarbenium tetrafluoroborate was found to be an efficient catalyst for the highly regioselective reductive ring opening of 4,6‐benzylidene acetals of hexopyranosides using DIBAL−H as the reducing agents to furnish the primary 6‐OH alcohols in good to excellent yield.

First enantioselective synthesis of salinipostin A, a marine cyclic enol-phosphotriester isolated from Salinispora sp

Salinipostins are cyclic enol-phosphotriesters isolated from a marine-derived Salinispora sp. as antimalarial compounds. Herein, the first enantioselective synthesis of salinipostin A was achieved. Organocatalyst-mediated asymmetric cyclopropanation and regioselective cyclopropane ring opening were the key steps.

Synthesis of the C1–C13 fragment of eribulin mesylate

Synthesis of the C1–C13 fragment of eribulin mesylate has been accomplished. It features a highly stereoselective construction of a trans-dihydropyran framework using three key reactions: (1) Sharpless epoxidation, (2) regioselective ring opening, and (3) olefin metathesis.

A Step‐Economic Synthesis of (S)‐(−)‐Juglomycin C and (S)‐(−)‐NHAB by Dötz Benzannulation and Convergent Deprotections

AbstractA step‐economic stereoselective synthesis of (S)‐(−)‐juglomycin C and (S)‐(−)‐NHAB is described. The synthesis features Dötz benzannulation reaction to readily assemble the desired naphthalene structure. The key alkyne fragment was synthesized via a Jacobsen hydrolytic kinetic resolution of racemic epoxide followed by regioselective ring opening. The convergent quinone formation and TBS group removal with ceric ammonium nitrate (CAN) and also AlCl3‐mediated demethylation and tert‐butyl group removal in a convergent deprotection are notable features in the synthesis.

Scandium‐Triflate‐Catalyzed Regioselective Ring Opening of Purines with Aminocyclopropanes

AbstractAn efficient route to acyclic purine nucleoside analogues with an amino group at the C1′ position of the side chains has been reported. Using Sc(OTf)3 as the catalyst, the ring‐opening reaction of purines with aminocyclopropanes afforded acyclic nucleoside analogues with moderate to good yields and in a regioselective manner. Furthermore, phenyl cyclopropane also gave the desired acyclic nucleoside analogue with a phenyl linked at C1′ position. Furthermore, generation of a penciclovir analogue may also occur from the ring‐opening product via a reduction reaction.

Alternative total synthesis of dendrodolide-L

A new synthetic route for the total synthesis of dendrodolide-L has been developed from known chiral epoxides. The key reactions involved in this synthesis are regioselective ring-opening of epoxide, Yamaguchi esterification and ring-closing metathesis reactions (RCM) to result the target compound.

Recent Advances in the Chemistry of Doubly Activated Cyclopropanes: Synthesis and Reactivity

Diactivated cyclopropanes containing two geminal electron withdrawing groups, commonly called as ‘Doubly Activated Cyclopropanes’ are useful synthons for the synthesis of many interesting natural products and functionalized molecules. These geminal electron withdrawing groups (EWG’s) facilitate the regioselective ring opening of cyclopropanes by polarizing the C-C bond adjacent to it. This polarization also allows them to undergo 1,3 dipolar cycloaddition reactions when substituted with a suitable electron donor substituent at the adjacent carbon (donor-acceptor cyclopropanes) in the presence of suitable dipolarophiles. In this review, we discuss the recent advances in the chemistry of doubly activated cyclopropanes: their synthesis, reactions and applications in total synthesis.

Total Synthesis of Pactalactam, an Imidazolidinone-Type Pactamycin Analogue.

The first total synthesis of pactalactam was accomplished using substrate-controlled stereoselective aziridination and regioselective aziridine ring-opening to construct three continuous amino groups on an octasubstituted cyclopentane core. The cyclopentane framework was obtained by ring-closing metathesis and aldol coupling using a l-threonine-derived oxazoline compound. Cyclic urea formation, m-acetylphenyl group introduction by Chan-Lam coupling, and primary alcohol-selective acylation yielded the reported pactalactam structure. The presence of pactalactam in the fermentation broth of pactamycin-producing bacteria was also confirmed.

Synthesis of Highly Substituted Azepanones from 2 H-Azirines by a Stepwise Annulation/Ring-Opening Sequence.

Bicyclic aziridines possessing a 1-azabicyclo[4.1.0]heptan-2-one core were prepared from 2 H-azirines by a stepwise annulation sequence involving a diastereoselective allylindanation, an N-acylation, and a ring-closing metathesis to construct the six-membered ring. After hydrogenation or functionalization of the olefin, regioselective ring opening of the resulting azabicyclic compounds with carboxylic acids (or sulfur nucleophiles) afforded highly substituted azepanones possessing an ester moiety or a trifluoromethyl group and a tetrasubstituted carbon at the α and β positions of the nitrogen atom, respectively.

Synthesis and catalytic antioxidant activity of functionalized chalcogen-containing GPx mimics

The synthesis and the evaluation of the thiol peroxidase like antioxidant properties of β-functionalized symmetric and non-symmetric organochalcogenides have been explored. The tested catalysts were synthesized exploiting the reactivity of strained heterocycles with silyl chalcogenides. Oxygen-, nitrogen-, and sulfur-containing selenides and tellurides were efficiently achieved from the corresponding epoxides, aziridines, and thiiranes through mild and regioselective ring opening reactions. The thiol peroxidase catalytic activity was investigated by using the dithiothreitol (DTT) oxidation model. The results showed that the nature of the β-substituent plays a crucial role in modulating the catalytic properties of the studied GPx mimics. This effect can be reasonably ascribed to the presence of chalcogen bonding interactions involving the selenium or the tellurium atom and the heteroatom (O, S) placed on the moiety at C-2.

Phosphazene-Catalyzed Regioselective Ring-Opening Polymerization of rac-1-Methyl Trimethylene Carbonate: Colder and Less is Better

The regioselective organocatalytic ring-opening polymerization (ROP) of a 6-membered cyclic carbonate, rac-1-methyl trimethylene carbonate, was studied using phosphazene base (t-BuP2) as the princi...

Stereoselective total synthesis of C2-symmetric natural products pyrenophorol and its derivatives

A stereoselective total synthesis of 16-membered C2-symmetric macrodiolide Pyrenophorol, Tetrahydropyrenophorol and 4,4-diacetylpyrenophorol have been accomplished. The synthesis started from commercially available L-Aspartic acid and the key reactions involved are regioselective epoxide opening, CBS reduction, Pinnick oxidation and Mitsunobu dilactonization.

Lewis Acid-Promoted Regio- and Diastereoselective Cross-Coupling of Aryl-Substituted 1,2-Diols and Boronic Acids.

A Lewis acid-promoted highly regio- and diastereoselective C(sp3)-C(sp2) cross-coupling reaction between unprotected aryl-substituted 1,2-diols and styryl-, aryl-, heteroaryl-, and polyarylboronic acids has been developed in a one-pot procedure. The regioselective opening of aryl-substituted cyclic boronic esters promoted by a Lewis acid followed by subsequent intramolecular 1,4-transfer of the carbon ligand from boron to a resonance-stabilized benzylic carbenium ion minimizing the allylic 1,3-strain in a stereoselective fashion led to the corresponding α-substituted syn-phenylethyl alcohols. The synthetic utility of the method was illustrated by a short and efficient enantioselective synthesis of cherylline diethyl ether (-)-16.