Olefin Cross‐Metathesis: Studies towards the Total Synthesis of (+)‐Bitungolide F

A stereoselective synthesis of (5S,6S)‐6‐[(2S,5S,7R,8E,10E)‐5‐(benzyloxy)‐7‐{[(tert‐butyl)dimethylsilyl]oxy}‐11‐phenylundeca‐8,10‐dien‐2‐yl]‐5‐ethyl‐5,6‐dihydro‐2H‐pyran‐2‐one (=(+)‐9‐O‐benzyl‐11‐O‐[(tert‐butyl)dimethylsilyl]bitungolide F) is reported. The strategy involves Gilman reaction, olefin cross‐metathesis, and Horner? Wadsworth? Emmons olefination as key steps.     

The Stereoselective Total Synthesis of (6S)‐5,6‐Dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one via Prins Cyclization

The stereoselective total synthesis of an antiproliferative and antifungal α‐pyrone natural product (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and ring‐closing metathesis reaction.     

Two Rare α‐Pyrone (=2H‐Pyran‐2‐one) Derivatives from Gentiana rhodantha Franchet

Two new rare α‐pyrone (=2H‐pyran‐2‐one) derivatives, rhodanthpyrones A and B ( 1 and 2 , resp.), together with fourteen known compounds, 3 – 16 , were isolated from the whole plants of Gentiana rhodantha. The structures of these compounds were elucidated by spectroscopic analyses. This is the first report on the occurrence of α‐pyrone derivatives in the genus Gentiana.     

Sequential Ugi Four‐Component Reaction (4‐CR)/CH Activation Using (Diacetoxyiodo)benzene for the Synthesis of 3‐(Diphenylmethylidene)‐2,3‐dihydro‐1H‐indol‐2‐ones

A sequential Ugi four‐component reaction (4‐CR)/C? H activation using (diacetoxyiodo)benzene is reported. This process is a five‐component reaction of aromatic aldehydes, aniline derivatives, isocyanides, phenylpropiolic acid (3‐phenylprop‐2‐ynoic acid), and (diacetoxyiodo)benzene for the synthesis of 3‐(diphenylmethylidene)‐2,3‐dihydro‐1H‐indol‐2‐ones. This procedure offers several advantages such as good yields, high bond‐forming efficiency, selectivity, and short reaction times.     

Environmentally Sustainable and Chemo‐selectively Favorable Synthesis of Substituted 2H‐Pyran‐2‐ones in Water under MWI

In this paper, a novel synthesis of diversely substituted 2H‐pyran‐2‐ones via the tandem reaction of 3‐hydroxyhexa‐4,5‐allenic esters in water under the promotion of MWI has been developed. Compared with those reactions carried out in organic solvents, water mediated synthesis of poly‐substituted 2H‐pyran‐2‐ones is not only environmentally sustainable, but also chemo‐selectively favorable.     

A One‐Pot Biginelli Synthesis of 6‐Unsubstituted 5‐Aroylpyrimidin‐2(1H)‐ones and 6‐Acetyl‐1,2,4‐triazin‐3(2H)‐ones

The three‐component Biginelli‐like cyclocondensation reaction of enamines 1 , urea, and aldehydes in dioxane/acetic acid efficiently afforded the corresponding 6‐unsubstituted 3,4‐dihydropyrimidin‐2(1H)‐ones 2 in good yields (Scheme 1, Table). The corresponding reaction of azaenamine (=hydrazone) 7 with benzaldehyde and urea afforded 6‐acetyl‐1,2,4‐triazin‐3(2H)‐ones in good yields (Scheme 3).     

Sesterterpenes and 2H‐Pyran‐2‐ones (=α‐Pyrones) from the Mangrove‐Derived Endophytic Fungus Fusarium proliferatum MA‐84

Two new tricyclic sesterterpenes, fusaprolifins A and B ( 1 and 2 ), and three new 2H‐pyran‐2‐one derivatives, prolipyrones A – C ( 3 – 5 ), were isolated and characterized from Fusarium proliferatum MA‐84, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Bruguiera sexangula. In addition, two known sesterterpenes, terpestacin ( 6 ) and fusaproliferin ( 7 ), and one known 2H‐pyran‐2‐one derivative, gibepyrone D ( 8 ), were also identified. The structures of these compounds were elucidated by detailed spectroscopic analyses. Fusaprolifin A ( 1 ) showed moderate activity against brine shrimp (Artemia salina), with a lethality rate of 49.5% at 100 μg/ml, while fusaprolifin B ( 2 ) showed weak activity.     

Preparation of Some Novel,Highly Unstable Chain Conjugated 2H‐Pyran‐5‐carboxylates

Aldol condensations of conjugated unsaturated β‐ketoesters and unsaturated aldehydes gave chain conjugated 2H‐pyran‐5‐carboxylates.     

Ring Opening of 2‐(Benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones and 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones

Substituted 2‐(benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones are unstable under alkaline and acidic conditions, undergoing opening of the benzoxazinone ring. 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones show similar degradation under alkaline conditions, while replacement of Br at C(2) to give 2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐ones was observed only under mild alkaline conditions. Mechanisms of ring opening and degradation to 2‐aminophenol derivatives are proposed.     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

A Convenient Synthesis of 2,3‐Dihydro‐3‐methylidene‐1H‐isoindol‐1‐ones by Reaction of 2‐Formylbenzo­nitriles with Dimethyloxosulfonium Methylide

A facile method for the synthesis of 2,3‐dihydro‐3‐methylidene‐1H‐isoindol‐1‐one and its derivatives carrying substituent(s) at C(5) and/or C(6) has been developed. The reaction of 2‐formylbenzonitrile ( 1a ) with dimethyloxosulfonium methylide, generated by the treatment of trimethylsulfoxonium iodide with NaH in DMSO/THF at 0°, resulted in the formation of 2,3‐dihydro‐3‐methylidene‐1H‐isoindol‐1‐one ( 2a ) in 77% yield. Similarly, six 2‐formylbenzonitriles carrying substituent(s) at C(4) and/or C(5), i.e., 1b – 1g , also gave the corresponding expected products 2b – 2g in comparable yields.     

Rhodium‐Catalyzed (5+1) Annulations Between 2‐Alkenylphenols and Allenes: A Practical Entry to 2,2‐Disubstituted 2H‐Chromenes

Readily available alkenylphenols react with allenes under rhodium catalysis to provide valuable 2,2‐disubstituted 2H‐chromenes. The whole process, which involves the cleavage of one C? H bond of the alkenyl moiety and the participation of the allene as a one‐carbon cycloaddition partner, can be considered a simple, versatile, and atom‐economical (5+1) heteroannulation. The reaction tolerates a broad range of substituents both in the alkenylphenol and in the allene, and most probably proceeds through a mechanism involving a rhodium‐catalyzed C? C coupling followed by two sequential pericyclic processes.     

Synthesis of 4‐fluoroalkyl‐2H‐pyrido [1, 2‐a] pyrimidin‐2‐ones from 2, 2‐dihydropolyfluoroalkanoic acids

In the presence of N, N′‐dicyclohexylcarbodiimide, 2‐aminopyridine and its derivatives (2) condensed with 2, 2‐di‐hydropolyfluoroalkanoic adds (1) to give the corresponding amides. Subsequent intramolecular Micheal addition‐elimination reactions of the fluorine‐containing amides under basic conditions gave 4‐fluoroalkyl‐2H‐pyrido[1,2‐a]pyrimidin‐2‐ones (3) in good yields.     

Photocyclodimerization of 5‐Methyl‐2H‐pyran‐3(6H)‐one

The structures of the main products resulting from photocyclodimerization of the title compound 2 and of other 3‐methyl‐substituted ‘oxacyclohex‐2‐en‐1‐ones’ (=dihydropyranones) were determined by X‐ray crystallography. In connection, the ¹³C‐NMR chemical shifts of the cyclobutane C‐atoms of these dimers allow a clear differentiation between head‐to‐head and head‐to‐tail regioisomers, all structurally related to those of isophorone ( 1 ).     

Palladium‐Catalyzed Intramolecular CH Difluoroalkylation: Synthesis of Substituted 3,3‐Difluoro‐2‐oxindoles

The synthesis of 3,3‐difluoro‐2‐oxindoles through a robust and efficient palladium‐catalyzed C? H difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate‐determining step for this process.     

Stereoselective Synthesis of 1,3‐Diaminotruxillic Acid Derivatives: An Advantageous Combination of CH‐ortho‐Palladation and On‐Flow [2+2]‐Photocycloaddition in Microreactors

The stereoselective synthesis of ε‐isomers of dimethyl esters of 1,3‐diaminotruxillic acid in three steps is reported. The first step is the ortho‐palladation of (Z)‐2‐aryl‐4‐aryliden‐5(4H)‐oxazolones 1 to give dinuclear complexes 2 with bridging carboxylates. The reaction occurs through regioselective activation of the ortho‐C?H bond of the 4‐arylidene ring in carboxylic acids. The second step is the [2+2]‐photocycloaddition of the C?C exocyclic bonds of the oxazolone skeleton in 2 to afford the corresponding dinuclear ortho‐palladated cyclobutanes 3 . This key step was performed very efficiently by using LED light sources with different wavelengths (465, 525 or 625 nm) in flow microreactors. The final step involved the depalladation of 3 by hydrogenation in methanol to afford the ε‐1,3‐diaminotruxillic acid derivatives as single isomers.     

A New Solution—phase Parallel Synthesis of 2—Alkyamino—3—aryl—5—phenylmethylene—3,5—dihydro—4H—imidazol—4—ones

Thirteen new 2-alkylaminoimidazolones(4) wre rapidly synthesized by a new solution-phase parallel synthetic method,which includes aza-Wittig reaction of iminophosphorane(1) with aromatic isocyanate to give carbodi-imide(2) and subsequent reaction of 2 with various aliphatic primary amine in a parallel fashion.The products were confirmed by ^1H NMR,MS,IR and X-ray crystallographic analysis.The unusual selectivity of the cyclization was probably due to the deometry of the guanidine intermediate.     

Pentafulvene for the Synthesis of Complex Natural Products: Total Syntheses of (±)‐Pallambins A and B

The first total syntheses of pallambins A and B are enabled by the use of pentafulvene in an unprecedented Diels–Alder reaction. After elaboration of the adduct through chemoselective cyclopropanation, strategic C? H insertion affords the dense tetracyclic core of the natural products. 1,3‐Dipolar cycloaddition and palladium(II)‐catalyzed alkoxycarbonylation were leveraged for the construction of the hexacyclic scaffold en route to both natural products.     

Total Synthesis of (+)‐Machaeriols B and C and of Their Enantiomers with a Cannabinoid Structure

An efficient and concise synthesis of the biologically interesting (+)‐machaeriol B ( 2 ) and its enantiomer 5 was accomplished from O‐phenylhydroxylamine ( 7 ) in four steps (Scheme 2). In addition, the first total synthesis of natural (+)‐machaeriol C ( 3 ) and its enantiomer 6 was achieved from the readily available ester 15 in eight steps (Scheme 4). The key strategies in the syntheses of 2 and 5 involved benzofuran formation through a [3,3]‐sigmatropic rearrangement and trans‐hexahydrodibenzopyran formation by a domino aldol‐type/hetero‐Diels–Alder reaction. In the case of 3 and 6 , the key steps were stilbene formation by a Horner–Wadsworth–Emmons reaction and trans‐hexahydrodibenzopyran formation by domino reactions.     

Synthesis of 2‐Aryl‐2,3‐dihydro‐3‐sulfanyl‐1H‐isoindol‐1‐ones by Pummerer‐Type Cyclization of N‐Aryl‐2‐(sulfinylmethyl)benzamides

An efficient method for the synthesis of 2‐aryl‐2,3‐dihydro‐3‐sulfanyl‐1H‐isoindol‐1‐ones 1 via Pummerer‐type cyclization of N‐aryl‐2‐(sulfinylmethyl)benzamides 2 is described. Thus, treatment of these sulfinyl‐benzamides 2 , easily prepared from 2‐(bromomethyl)benzoates 3 in three steps, with Ac₂O at ca. 100° resulted in the formation of the desired isoindolones 1 in generally good yields.