Facile syntheses of 2-substituted 3-cyanochromones

A simple and general route to 3-cyanochromones containing various substituents on position 2 of the ring is developed. The method is based on condensation of 3-(2-hydroxyphenyl)-3-oxopropionitrile with acid chlorides or anhydrides in pyridine at room temperature.     

Facile syntheses of 3-spiro- and 3,6-bridged 2,5-piperazinediones

The intramolecular addition of hydroxyl group of 3-(3-hydroxyl)propylidene-2,5-piperazinedione to 3-position and the same substitution of 3-(3-hydroxy)propyl derivative to 6-position gave the corresponding 3-spiro- and 3,6-bridged 2,5-piperazinediones, respectively.     

Facile syntheses of unsolvated UI3 and tetramethylcyclopentadienyl uranium halides

In the course of comparing the reaction chemistry of (C5Me5)3U, 1, and its slightly less crowded analogue (C5Me4H)3U, 2, new syntheses of UI3, (C5Me4H)3U, (C5Me4H)3UCl, 3, and (C5Me5)3UCl, 4, have been developed. Additionally, (C5Me4H)3UI, 5, and (C5Me4H)2UCl2, 6, have been identified for the first time. A facile synthesis of unsolvated UI3 is reported that proceeds in high yield with inexpensive equipment from iodine and hot uranium turnings. Both UI3 and UI3(THF)4 react with KC5Me4H in toluene to make unsolvated (C5Me4H)3U in higher yield than in previous reports that involve reduction of tetravalent (C5Me4H)3UCl, 3. A more atom-efficient synthesis of complex 3 is also reported that proceeds from reduction of t-BuCl, PhCl, or HgCl2 by 2. Similarly, (C5Me4H)3U reacts with PhI or HgI2 to generate (C5Me4H)3UI. These studies also provided a basis to improve the synthesis of (C5Me5)3UCl from 1 by employing t-BuCl or HgCl2 as the halide source. Like (C5Me5)3UCl, the (C5Me4H)3UCl complex reacts with HgCl2 to form (C5Me4H)2 and (C5Me4H)2UCl2, 6, but unlike (C5Me5)3UX (X = Cl or I), the less substituted (C5Me4H)3UX complexes do not reduce t-BuCl or PhX. The synthesis of 6 from (C5Me4H)MgCl x THF and UCl4 is also included.     

Facile syntheses of 2,4,6-cycloheptatrienyl ketones

The synthesis of the 2,4,6-cycloheptatrienyl ketones $\text{1a}$–$\text{1e}$ by two alternative routes is reported: Route 1): The adducts $\text{3a–c}$ from the phenyl(trimethylsiloxy)-acetonitriles $\text{2a–c}$, known as “umpolung” reagents, and tropylium tetrafluoroborate are cleaved by triethylammonium fluoride to form the aromatic cycloheptatrienyl ketones $\text{1a}$–$\text{1c}$. Route 2): the phenyl, methyl, and cyclopropyl ketone ($\text{1a}$, $\text{1d}$, $\text{1e}$) are prepared by treatment of the acid chloride $\text{7}$ with the corresponding organomanganese iodides RMnI ($\text{8a}$, $\text{8d}$, $\text{8e}$). The Fe-catalyzed coupling reaction of the acid chloride $\text{7}$ with a Grignard reagent was also used for the preparation of ketone $\text{1b}$.     

Facile syntheses of monodisperse ultrasmall Au clusters

During our effort to synthesize the tetrahedral Au20 cluster, we found a facile synthetic route to prepare monodisperse suspensions of ultrasmall Au clusters AuN (N < 12) using diphosphine ligands. In our monophasic and single-pot synthesis, a Au precursor ClAu(I)PPh3 (Ph = phenyl) and a bidentate phosphine ligand P(Ph)2(CH2)(M)P(Ph)2 are dissolved in an organic solvent. Au(I) is reduced slowly by a borane-tert-butylamine complex to form Au clusters coordinated by the diphosphine ligand. The Au clusters are characterized by both high-resolution mass spectrometry and UV-vis absorption spectroscopy. We found that the mean cluster size obtained depends on the chain length M of the ligand. In particular, a single monodispersed Au11 cluster is obtained with the P(Ph)2(CH2)3P(Ph)2 ligand, whereas P(Ph)2(CH2)(M)P(Ph)2 ligands with M = 5 and 6 yield Au10 and Au8 clusters. The simplicity of our synthetic method makes it suitable for large-scale production of nearly monodisperse ultrasmall Au clusters. It is suggested that diphosphines provide a set of flexible ligands to allow size-controlled synthesis of Au nanoparticles.     

Facile biomimetic syntheses of the azaspiracid spiroaminal

The azaspiracid natural products display a common spiroaminal-containing terminal domain that has inspired the development of two new methods for spiroaminal syntheses—a Staudinger reduction-aza-Wittig process and a double intramolecular hetero-Michael addition. These effective laboratory approaches proceed through imine and enamine intermediates that may reflect transient biogenetic species.     

Facile syntheses of homothia‐ and homoazacalixarenes

Decahomotetrathiacalix[6]arenes were conveniently prepared from the 2:2 cyclization reactions of bis(chloromethyl)phenol‐formaldehyde trimers with 1,2‐ethanedithiol in high yields. In contrast, the simi lar reactions of the trimers with 1,3‐propanedithiol instead of 1,2‐ethanedithiol gave 1:1 macrocycles, hexahomodithiacalix[3]arenes, in good yields. Homoazacalixarenes were also prepared from the analogous reactions using piperazines. These macrocycles adopt a cone‐like form as a preferable conformation in solution.     

Facile syntheses of homoleptic diarylmercurials via arylboronic acids

A general procedure for the syntheses of diarylmercurials is presented. Reactions proceeded in isopropanol in the presence of a base and arylboronic acid. With one exception, all reactions proceeded in good to excellent yields, and this procedure was applicable to a variety of aromatic and heteroaromatic boronic acids. Products were characterized by multinuclear NMR spectroscopy and microanalysis, and investigated by DFT calculations. The structure of di(4-pyridyl)mercury (6) was further authenticated by X-ray crystallography. Combined with previous work on the formation of arylgold(I) complexes via arylboronic acids, this procedure may be generally useful for the arylation of late transition metals.     

Facile syntheses of quater-, penta-, and sexipyrroles

alpha,alpha-Linked oligopyrroles are attractive precursors for both expanded porphyrin and conducting polymer chemistry. We demonstrate facile methods for synthesizing quater-, penta-, and sexipyrroles from more readily available bi- and terpyrrole intermediates. These products demonstrate stability in their brightly colored oxidized forms, while reduction using borohydride reagents gives the corresponding all-pyrrole oligomers, which oxidize readily in air. The oxidized quater- and sexipyrroles were characterized by single-crystal X-ray diffraction analysis.     

Facile syntheses of surface-functionalized micelles and shell cross-linked nanoparticles

Block copolymer micelles and shell cross-linked nanoparticles (SCKs) presenting Click-reactive functional groups on their surfaces were prepared using two separate synthetic strategies, each employing functionalized initiators for the controlled radical polymerization of acrylate and styrenic monomers to afford amphiphilic block copolymers bearing an alkynyl or azido group at the α-terminus. The first route for the synthesis of the azide-functionalized nanostructures was achieved via sequential nitroxide-mediated radical polymerization (NMP) of tert-butyl acrylate and styrene, originating from a benzylic chloride-functionalized initiator, followed by deprotection of the acrylic acids, supramolecular assembly of the block copolymer in water and conversion of the benzylic chloride to a benzylic azide. In contrast, the second strategy utilized an alkynyl-functionalized reversible addition fragmentation transfer (RAFT) agent directly for the RAFT-based sequential polymerization of tetrahydropyran acrylate and styrene, followed by selective cleavage of the tetrahydropyran esters to give the α-alkynyl-functionalized block copolymers. These Click-functionalized polymers, with the functionality located at the hydrophilic polymer termini, were then self-assembled using a mixed-micelle methodology to afford surface-functionalized “Clickable” micelles in aqueous solutions. The optimum degree of incorporation of the Click-functionalized polymers was investigated and determined to be ca. 25%, which allowed for the synthesis of well-defined surface-functionalized nanoparticles after cross-linking selectively throughout the shell layer using established amidation chemistry. Functionalization of the chain ends was shown to be an efficient process under standard Click conditions and the resulting functional groups revealed a more “solution-like” environment when compared to the functional group randomly inserted into the hydrophilic shell layer. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5203–5217, 2006     

Facile one-pot syntheses of bromoacetylenes from bulky trialkylsilyl acetylenes

Because haloalkynes are versatile intermediates in synthetic chemistry, the development of new efficient methods for the conversion of 1-trialkylsilylacetylenes to haloacetylenes in situ remains desirable, especially when the corresponding terminal acetylenes are unstable. Using AgF and NBS, we have successfully transformed various 1-(trialkylsilyl)acetylenes, including bulky trialkylsilyl acetylenes, into bromoacetylenes in high yield. The reactions are chemoselective: triisopropylsilyl ethers were not deprotected under these conditions.     

Facile syntheses of 3-trifluoromethylthio substituted thioflavones and benzothiophenes via the radical cyclization

3-CF3 S substituted thioflavones and benzothiophenes were achieved via the reactions of AgSCF3 with methylthiolated alkynones and alkynylthioanisoles,respectively,promoted by persulfate.This protocol possesses good functional group tolerance and high yields.Mechanistic studies suggested that a classic two-step radical process was involved,which includes addition of CF3 S radical to triple bond and cyclization with SMe moiety.     

Facile syntheses of various per- or polyfluoroalkylated internal acetylene derivatives

Treatment of per- or polyfluoroalkylated vinyl iodides 5 with 2 equiv. of n-BuLi in THF produced the corresponding lithium acetylides in situ, which were transformed into zinc acetylides by the addition of ZnCl₂·TMEDA complex into the reaction mixture. The in situ generated zinc acetylides were exposed to the cross-coupling conditions such as ArI/cat. Pd(PPh₃)₄, reflux, 6-12 h, giving rise to the desired per- or polyfluoroalkylated acetylenes in high yields. In the case of trifluoromethylated acetylene, commercially available 2-bromo-3,3,3-trifluoropropene 6 could also be used instead of 5 as the starting material. In the acetylenes having a fluoroalkyl group and an aliphatic side chain, vinyl iodides 7, prepared by radical addition of perfluoroalkyl iodide to terminal acetylenes, were treated with t-BuOK at room temperature or at the reflux temperature of benzene, affording the desired compounds in good yields.     

Novel ring opening of aminoheterocycles: Facile syntheses of ω-alkylaminopentadienenitriles

2-Amino-1-alkylpyridinium and 2-amino-3-alkyl-thiazolium cations are converted by n-BuLi into ω-aminopentadienenitriles and 2-alkylaminovinyl thiocyanates, respectively.     

Facile syntheses of conformationally constrained analogues of lysine and homoglutamic acid

A facile divergent synthesis of the novel amino acid trans-4-aminoethyl-l-proline and trans-4-carboxymethyl-l-proline from commercially available trans-4-hydroxy-l-proline was developed. These conformationally constrained analogues of l-lysine and l-homoglutamic acid are useful proline templated amino acids (PTAAs) with potential applications in protein engineering and de novo protein design.     

Photoinduced reactions—LXXI: Photorearrangement of 3-hydroxyflavones to 3-aryl-3-hydroxy-1,2-indandiones

3-Hydroxyflavones (1) were found to undergo a novel photorearrangement to 3-aryl-3-hydroxy-1,2-indandiones (2) which were characterized as o-phenylenediamine adducts, 1-aryl-1-hydroxy-11H-indeno[1,2-b]quinoxalines (3). To the contrary, 3-methoxyflavone underwent photochemical intramolecular hydrogen transfer. Photochemical reactivities of several other flavonoids were examined. It appears that the 5-hydroxyl H-bonded to the 4-carbonyl causes photoresistance in flavonoids.     

Facile syntheses of oxazolines and thiazolines with N-acylbenzotriazoles under microwave irradiation

Microwave reactions of 2-amino-2-methyl-1-propanol (2) or 2-aminoethanethiol hydrochloride (4) with readily available N-acylbenzotriazoles 1a-j in the presence of SOCl(2) produced 2-substituted 2-oxazolines 3a-j in 84-98% yields and 2-substituted thiazolines 5a-i in 85-97% yields, respectively. With use of this method chiral oxazoline 6, bisoxazoline 7, bisthiazoline 8, and 5,6-dihydro-4H-1,3-oxazines 9 or 10 have also been prepared in 82-96% yields. These results demonstrate a new application of N-acylbenzotriazoles in the preparation of oxazolines and thiazolines under mild conditions and short reaction times with microwave irradiation.     

Microbial metabolism. Part 6. Metabolites of 3- and 7-hydroxyflavones

Fermentation of 3-hydroxyflavone (1) with Beauveria bassiana (ATCC 13144) yielded 3,4'-dihdroxyflavone (3), flavone 3-O-beta-D-4-O-methylglucopyranoside (4) and two minor metabolites. 7-Hydroxyflavone (2) was transformed by Nocardia species (NRRL 5646) to 7-methoxyflavone (5) whilst Aspergillus alliaceus (ATCC 10060) converted it to 4',7-dihydroxyflavone (6). Flavone 7-O-beta-D-4-O-metylglucopyranoside (7) and 4'-hydroxyflavone 7-O-beta-D-4-O-methylglucopyranoside (8) were the metabolic products of 7-hydroxyflavone (2) when fermented with Beauveria bassiana (ATCC 7159). One of the minor metabolites of 3-hydroxyflavone (1) was tentatively assigned a beta'-chalcanol structure (9). Compounds 4, 7 and 8 are reported as new compounds. Structure elucidation of the metabolites was based on spectroscopic data.