Efficient phenolic oxidations using μ-oxo-bridged phenyliodine trifluoroacetate

The excellent oxidizing behavior of the μ-oxo-bridged phenyliodine trifluoroacetate 1 is revealed during the phenolic oxidations mediated by hypervalent iodine(III) reagents. The use of the μ-oxo-bridged compound 1 instead of PhI(OAc)₂ (PIDA) and PhI(OCOCF₃)₂ (PIFA) during the oxidative cyclization of phenols involving carbon-oxygen, carbon-nitrogen, and carbon-carbon bond formations could produce spirocyclized cyclohexadienones in comparable or somewhat better yields. Thus, we have concluded that the unique reagent 1 is a promising alternative to PIDA and PIFA, and the use of reagent 1 as a reasonable choice is recommended for the hypervalent iodine(III)-mediated phenolic oxidations as well as other transformations.     

Enhancing the solubility for hypervalent ortho-sulfonyl iodine compounds

The synthesis and characterization of new hypervalent iodine reagents ArINTs (2a), ArIO (3a), and ArIO₂ (4a) (Ar=2-tert-butylsulfonyl-5-tert-butylphenyl) are described. These reagents are compared to previously reported analogous set of reagents Ar=2-tert-butylsulfonylphenyl and found to have significantly enhanced solubility and similar chemical reactivity. The X-ray crystal structures of 4a and of ArI (1a) (Ar=2-tert-butylsulfonyl-5-tert-butylphenyl) are discussed and compared. These reagents find use in atom and group transfer reactions.     

2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine as a new recyclable “iodoarene” for in situ generation of hypervalent iodine(III) reagent for α-tosyloxylation of enolizable ketones

The synthesis of 2,4,6-tris[(4-iodo)phenoxy)]-1,3,5-triazine 6, as a new recyclable nonpolymeric analogue of iodobenzene is achieved using the reaction of 2,4,6-trichloro-1,3,5-triazine with 4-iodophenol in the presence of KOH. The application of 6 as a recyclable ‘iodoarene’ is demonstrated for α-tosyloxylation of enolizable ketones via in situ generation of hypervalent iodine(III) species using PTSA and MCPBA as the terminal oxidant. The recyclability of the reagent 6 was possible owing to the facile recovery and reuse from the reaction mixture due to its near insolubility in methanol.     

Advances in the preparation of organofluorine compounds involving iodine and/or iodo-compounds

The intriguing properties of iodine have drawn the attention of organic chemists. In this paper, we will describe the recent development of stereo- and/or regioselective synthesis of fluorine-containing organic compounds employing hypervalent iodine fluorides such as ArIF₂ (1), IF₅ (22), and (E)-2-fluoro-alk-1-enyl-4-aryl iodonium salts R(F)C=C(H)IF-Ar (12). The electrochemical fluorination procedures involving iodo-compounds will also be presented to prepare fluoro-organic compounds.     

Synthesis of thietane nucleoside with an anomeric hydroxymethyl group

Thietane nucleoside 5 with an anomeric hydroxymethyl group was synthesized via the Pummerer reaction. The stereochemistry of the sulfoxide and the nature of the protecting group had no significant effect on the yield of the reaction. When a hypervalent iodine reagent was used, sulfide 16 with O-benzoyl protecting groups gave the ring-expanded nucleoside 21. Unfortunately, synthesized compound 6 did not exhibit anti-HSV activity.     

Mild and efficient Sonogashira couplings of 8-oxa- and 8-thiabicyclo[3.2.1]octanone derived alkenyl nonaflates

We demonstrate in this report that bicyclic alkenyl nonaflates (nonafluorobutanesulfonates) generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives are excellent substrates for Sonogashira couplings with alkynes. Employing CuI, Pd(OAc)₂, PPh₃ in DMF/i-Pr₂NH as standard reagents structurally diverse bicyclic nonaflates were coupled with phenyl acetylene in generally high yields. Particularly efficient are transformations of precursors 16, 18, and 20 bearing methyl groups at the bridgehead carbons, which furnished the expected enynes 17, 19, and 21 in approximately 90% yield. With respect to the alkyne component the scope of this palladium-catalyzed reaction seems also to be fairly broad. Thus, trimethylsilyl acetylene and propargyl alcohol could also be used, affording coupling products 22, 23, and 25 with high efficacy. The protocol of Grieco was applied to induce a domino coupling of tricyclic alkenyl nonaflate 14 with trimethylsilyl acetylene affording product 26 in moderate yield and as 1:1 mixture of the expected two diastereomers.     

Electrophilic (phenylsulfonyl)difluoromethylation of thiols with a hypervalent iodine(III)-CF2SO2Ph reagent

A hypervalent iodine(III)-CF₂SO₂Ph compound (3) has been successfully prepared with selective nucleophilic reaction using PhSO₂CF₂SiMe₃ reagent, and this previously unkown compound 3 was found to act as a new electrophilic (phenylsulfonyl)difluoromethylation reagent for a variety of S-nucleophiles under very mild reaction conditions.     

Enantioselective synthesis of (+)-anatoxin-a via enyne metathesis

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed by a series of nine chemical operations and in 27% overall yield from commercially available d-methyl pyroglutamate (12). The strategy featured the application of a new protocol for the diastereoselective synthesis of cis-2,5-disubstituted pyrrolidines bearing unsaturated side chains and an intramolecular enyne metathesis to provide the bridged bicyclic framework of 1. Thus, d-methyl pyroglutamate (12) was converted in five steps to 32, which underwent facile enyne metathesis to deliver the bicyclic diene 33. Selective oxidative cleavage of the less substituted carbon-carbon double bond in 33 followed by deprotection furnished (+)-anatoxin-a (1).     

Electrophilic trifluoromethylation of arenes and N-heteroarenes using hypervalent iodine reagents

The reaction of hypervalent iodine trifluoromethylating reagents with a variety of arenes and N-heteroarenes gives access to the corresponding trifluoromethylated compounds. In comparative studies, 1-trifluoromethyl-1,3-dihydro-3,3-dimethyl-1,2-benziodoxole (2) proved to be the superior to 1-trifluoromethyl-1,2-benziodoxol-3-(¹H)-one (1) for the direct aromatic trifluoromethylation. Depending on the individual substrates, additives such as zinc bis(trifluoromethylsulfonyl)imide or tris(trimethylsilyl)silyl chloride proved helpful in promoting the reactions. In the case of nitrogen heterocycles a pronounced tendency for the incorporation of the trifluoromethyl group at the position adjacent to nitrogen was observed.     

Synthesis of naturally occurring bioactive butyrolactones: maculalactones A-C and nostoclide I

Starting from citraconic anhydride (13), a simple multistep (9-10 steps) synthesis of naturally occurring butyrolactones maculalactone A (3), maculalactone B (1), maculalactone C (2) and nostoclide I (4) have been described with good overall yields via dibenzylmaleic anhydride (20) and benzylisopropylmaleic anhydride (27). The two anhydrides 20 and 27 were prepared by S_N2′ coupling reactions of appropriate Grignard reagents with dimethyl bromomethylfumarate (14), LiOH-induced hydrolysis of esters to acids, bromination of carbon-carbon double bond, in situ dehydration followed by dehydrobromination and chemoselective allylic substitution of bromoatom in disubstituted anhydrides 19 and 26 with appropriate Grignard reagents. The NaBH₄ reduction of these anhydrides 20 and 27 furnished the desired lactones 21 and 29, respectively. The lactone 21 on Knoevenagel condensation with benzaldehyde, furnished maculalactone B (1), which on isomerization gave maculalactone C (2). Selective catalytic hydrogenation of 1 gave maculalactone A (3). The conversion of lactone 29 to nostoclide I (4) is known.     

New antimitotic bicyclic peptides, celogentins D-H, and J, from the seeds of Celosia argentea

Six new bicyclic peptides, celogentins D-H (1-5) and J (6) have been isolated from the seeds of Celosia argentea, and the structures including its absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins E-H (2-5) and J (6) showed potent inhibition of tubulin polymerization, while the inhibitory activity of celogentin D (1) was modest. Structure-activity relationship study indicates that ring size of the bicyclic ring system including unusual β^s-Leu, Trp, and His residues would be important for their biological activity.     

Reactions promoted by [hydroxy(tosyloxy)iodo]benzene in pyrazino[1,2-b]isoquinolines

The hypervalent iodine reagent PhI(OH)OTs (HTIB) promoted oxidative demethylation of 1,4-hydroquinone methyl ethers to give quinones in a quantitative conversion. The efficacy of this reaction, that has been applied to simple arene compounds and to heterocyclic systems, such as 2-isopropoxycarbonyl-7,10-dimethoxy-pyrazino[1,2-b]isoquinoline-4-ones and 1,4-diones to get the corresponding 7,10-quinones (compounds 6-8), is similar to those promoted by CAN and does not require the presence of water. Instead of oxidative demethylation, HTIB promoted in 1-methoxy-pyrazino[1,2-b]isoquinoline-4-ones complex multi-step processes to give compounds 9 or 10.     

Synthesis and reactivity of Z and E functionalized allylic fluorides

The allylic fluorides 1 and 2 are used as models to study the effect of the allylic C-F bond on the diastereoselectivity of reactions occurring on the vicinal double bond, as well as the compatibility of this C-F bond with various reagents. The configurational stability of the Z double bonds in enals and enones 1 and 3 is noteworthy. This allowed us to perform various types of reactions (including thermal Diels-Alder cycloadditions) on derivatives 1 with full control of the Z geometry.     

Hydroarylation of bicyclic, unsaturated dicarboximides: access to aryl-substituted, bridged perhydroisoindoles

The C-C coupling of the two bicyclic, unsaturated dicarboximides 6 and 8 with aryl and hetaryl halides gave under reductive Heck conditions the 5-substituted N-phenylbicyclo[2.2.1]heptane-2,3-dicarboximides 7 and 9. Reduction of these imides opens a new access to the bridged perhydroisoindole derivatives 12 and 14 with prospective biological activity.     

The iron(III) chloride-mediated 1,4-addition of mercaptans to α,β-unsaturated ketones and esters under solvent free conditions

The 1,4-addition of various thiols to α,β-unsaturated ketones was completed rapidly in the presence of a catalytic amount (2-3 mol %) of anhydrous iron(III) chloride under solvent free conditions and an air atmosphere. Anhydrous iron(III) chloride is more active than that of other ferric salts. With more reactive and/or less steric reagents (1a-c and/or 2a-2c), expeditious conditions (short reaction times at room temperature) could be employed. With less reactive and/or steric reagents (1d-g and/or 2d-e), a slight increase in reaction time was required, but high yields were obtained. The FeCl₃ catalyst causes preferential interactions with α,β-unsaturated ketones present in the reaction.     

IBX in an ionic liquid: eco-friendly oxidation of 17α-methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone

An easily available hypervalent iodine(V) reagent, 2-iodoxybenzoic acid (IBX) immobilized in the ionic liquid [bmim][Br] was found to be an efficient and eco-friendly protocol for the oxidation of 17α-methylandrostan-3β,17β-diol (1). At ambient temperature oxidation of 1 with IBX gave mestanolone (2) in good yield and with an increased stoichiometric amount of IBX, oxidation adjacent to the carbonyl functionality (α,β-unsaturation) occurred to give dehydrogenated 17β-hydroxy-17α-methyl-Δ¹-androsten-3-one (3) as the major product in a one-pot reaction. The product is easily obtained by extraction with diethyl ether and evaporation of the solvent.     

Microwave-assisted regioselective synthesis of natural 6-prenylpolyhydroxyisoflavones and their hydrates with hypervalent iodine reagents

Microwave-assisted oxidative rearrangement of 3′-iodotetraalkoxychalcones with hypervalent iodine such as [hydroxy(tosyloxy)iodo]benzene or [bis(trifluoroacetoxy)iodo]benzene, followed by microwave-mediated hydrolysis and in situ cyclization of the resultant acetals gave 6-iodotrialkoxyisoflavones. Pd(0)-catalyzed coupling reaction of the 6-iodoisoflavones with 2-methyl-3-butyn-2-ol under microwave irradiation gave 6-alkynylisoflavones, whose hydrogenation gave the respective hydrates of wighteone, lupisoflavone and derrubone. Wighteone (1a), lupisoflavone (1b) and derrubone (1c) were obtained by dehydration of their respective hydrates under microwave irradiation.     

Preparation of sila-functional 3-sila-1-thiacyclohexanes

First sila-functional heterocycles 7 and 9 with Si and S atoms in 1,3-position bearing the reactive X group at silicon (X = i-PrO, F) were readily prepared from the corresponding phenyl-protected cycle 6 in good yields via Ph-Si bond cleavage by electrophilic reagents. Treatment of i-propoxy derivative 7 with LiAlH₄ gave heterocycle 8 with Si-H bond.     

Syntheses, structures, luminescence, and magnetism of four 3D lanthanide 5-sulfosalicylates

Four 3D lanthanide(III) complexes with 5-sulfosalicylic acid (H₃SSA) as bridging ligands, Ln(SSA)(H₂O)₂ [Ln=Ce(III) (1), Pr(III) (2), Nd(III) (3) and Dy(III) (4)], have been synthesized and characterized by elemental analysis, IR, XRD and single-crystal X-ray diffraction. X-ray structural analysis reveals that isostructral complexes 1-4 possess 3D structures with 4⁶6⁴ topology. Complexes 1 and 2 exhibit broad intraligand fluorescent emission bands. Complexes 3 and 4 not only display intraligand fluorescent emission bands, but also present Nd(III) characteristic emission in the near-IR region and sensitized luminescence of Dy(III) ions in the visible region, respectively. Variable-temperature magnetic susceptibility measurements of 2-4 have been studied over the temperature range of 4-300 K.     

The synthesis, spectroscopic, electrochemical and X-ray diffraction characterization of novel bridged ferrocene precursors for use in self-assembled monolayers

The synthesis of 1,6-diferrocenylhexane-1,6-dione (I), 1-ferrocenylcarbonyl-2-ferrocenylcyclopentene (II) and 1,6-diferrocenylhexane (III) is reported. All three compounds were characterized by ¹H NMR, ¹³C NMR, and infra-red spectroscopy, mass spectrometry, cyclic voltammetry and chronoamperometry. Compounds I and III each exhibit a single two electron transfer, while compound (II) exhibits two single electron transfers. Compounds (I) and (II) were further studied by single crystal X-ray diffraction. In compound (I), both carbonyl groups are in plane with the adjacent ferrocenyl Cp ring. For compound (II) one of the ferrocenyl Cp rings is coplanar with the carbonyl group, the other with the double bond of the cyclopentene ring, but the CO moiety and the double bond are basically perpendicular to each other.