New building blocks for fluorinated bioimidazole derivatives II: preparation of beta-fluorourocanic acids

Replacement of vinyl hydrogen with fluorine is based on addition of an FBr equivalent to a double bond followed by HBr elimination. This sequence has been adapted to prepare 3-fluoro-3-imidazolyl-propenoic acids (beta-fluorourocanic acids), and the related fluorinated imidazolyl propenals and prop-2-en-1-ols, from urocanic acid. Tritylation of the imidazole nitrogen was necessary for successful addition of "FBr" to the double bond, and prior reduction of the carboxyl group to the alcohol was required to provide the desired chemoselectivity in the elimination of HX. Reoxidation and deprotection produced the fluorinated urocanic acids.     

New and efficient syntheses of alpha-iodo-alpha,alpha-difluoro- and beta-iodo-alpha,alpha,beta,beta-tetrafluorocarboxylic acid derivatives as useful building blocks for making functional fluoro compounds

Perfluoroolefins reacted with I-Cl and ClSO(3)H under mild conditions to give R(F)CFICF(2)OSO(2)Cl, which could be readily converted into various alpha-iodo-perfluorocarboxylic acid derivatives or telomerized with tetrafluoroethylene to I(CF(2)CF(2))(n)()OSO(2)Cl. Ring-opening reaction of perfluoroalkoxypentafluorocyclopropane with iodine at 240 degrees C produced ICF(2)CF(2)COF, which was quenched by alcohol, water, or NH(3) to give beta-iodo-alpha,alpha,beta,beta-tetrafluorocarboxylic acid derivatives. These functional fluorinated iodides can be used as building blocks for making selectively fluorinated compounds.     

Enaminones as building blocks in heterocyclic synthesis: New syntheses of nicotinic acid and thienopyridine derivatives

Reacting 1,3‐diphenyl‐propan‐2‐one with equimolecular amount of dimethylformamide dimethylacetal afforded the enaminone 4. This when reacted with another equimolecular amount of dimethylformamide dimethylacetal afforded the dienaminone 5. Compound 4 condenses with cyanothioacetamide and with cyanoacetamide to yield 2‐thioxo‐ and 2‐oxo‐pyridine‐3‐carbonitrile derivatives 6a,b respectively. Compound 6a reacted with α‐chloroacetone 8 to yield the thieno[2,3‐b]pyridine derivative 10 that cyclized further into 4,7,8‐trisubstituted pyrido[2′,3′:2,3] thieno[4,5‐d]pyrimidine 12. Compound 4 also afforded 2,5,6‐trisubstituted nicotinic acid ethyl ester 13 by reaction with ethyl acetoacetate in acetic acid in the presence of ammonium acetate. The dienaminone 5 reacted with acetic acid, ammonium acetate/acetic acid, phenylhydrazine and 5‐amino‐3‐methylpyrazole yielding 3,5‐diphenyl‐pyran‐4‐one 15a , 3,5‐diphenyl‐1H‐pyridin‐4‐one 15b and 1,3,5‐trisubstituted pyridin‐4‐ones 16a‐b.     

Synthesis of novel enantiopure fluorinated building blocks from acyclic chiral allylsilanes

[reaction: see text] Homochiral beta-fluorinated gamma,delta-unsaturated carboxylic acids with an allylic fluorinated stereogenic center are available from the corresponding enantiopure allylsilanes. The key step for introduction of the fluorine substituent is an electrophilic fluorodesilylation reaction carried out in the presence of Selectfluor. Reduction of the resulting beta-fluorinated pentenoic acid into the corresponding fluorinated alcohol was also performed leading to the formation of an enantiopure second-generation fluorinated building block.     

2-Amino-3,4-diethylpyrrole derivatives: new building blocks for coiled structures

The synthesis of a multicomponent, mixed oligomer containing alpha-aminopyrrole is described; this system adopts a coiled structure in the solid state and serves as a prototype of a possible new class of hydrogen bond based helicates.     

Immobilized porcine liver esterase: a convenient reagent for the preparation of chiral building blocks.

A simple method for the effective, covalent, immobilization of porcine liver esterase ( PLE ) is described, and the application of this reagent for the preparation of chiral building blocks on a 50 – 500 mmol scale is demonstrated.     

A convenient preparation of taxoid right-half building blocks

Wieland–Miescher ketone derived unsaturated diols 4 reacted with Pb(OAc)₄ to furnish tricyclic enolether intermediate 6 which upon ozonolysis gave access to useful synthetic intermediates such as bicyclic lactone 7, methyl furanoside 8 and triol 9 (taxoid right-half precursors), depending on the solvent used during the ozonolysis and the nature of the following synthetic operation.     

New synthesis of imidazole derivatives from cyanobenzenes

An efficient access to 4-aryl imidazole scaffolds is described in two steps and one operation. Cyanoaryl-imidazolines are easily obtained by a (3?+?2) heterocyloaddition involving cyanobenzenes as dipolarophiles and a non-stabilized azomethine ylide as an electron-rich 1,3-dipole. Oxidation of the crude mixture affords an efficient two-steps access to the corresponding imidazoles.     

Boronnitrogen compounds : LXXXIX. New boron derivatives of pyrazole and imidazole

New monomeric N-borylated pyrazole and imidazole derivatives have been synthesized and some of their characteristic features have been explored. The suggested structures are supported by spectroscopic data.     

Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids

Enantiopure 1-acyl-3-hydroxyl-4-CF₂H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF₃-azetidin-2-ones serve as versatile intermediates for the syntheses of CF₂- and CF₃-containing α-hydroxy-β-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF₂H-β-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure 4-formyl-β-lactam that is prepared through [2+2] cycloaddition of acetoxyketene to a 3-methyl-2-butenaldimine, followed by enzymatic optical resolution and ozonolysis. (+)-3-Hydroxy-4-CF₃-β-lactams and (−)-3-hydroxy-4-CF₃-β-lactams can also be readily obtained in enantiopure form through [2+2] cycloaddition of a CF₃-imine with a ketene, followed by enzymatic optical resolution. Practical processes for the preparations of these enantiopure 3-hydroxy-4-R_f-β-lactams as well as their synthetic applications are described.     

Synthesis of reactive cytidine derivatives as building blocks for cross-linking oligonucleotides

6-Vinylcytidine derivative (1) possessing good Michael acceptor properties has been synthesized through C-6 formylation and subsequent Wittig reaction. In view of introducing the reactive nucleoside into the oligonucleotide sequence, protection of the vinyl group as ethylthio derivative was proved to be effective for the masking and subsequent regeneration of the reactive vinyl moiety.     

Lipase mediated resolution of 1,3-butanediol derivatives: chiral building blocks for pheromone enantiosynthesis. Part 3

(R,S)-1,3-Butanediol 5 was kinetically resolved by enzymatic acetylation with vinyl acetate under the presence of Chirazyme™ L-2, c–f, yielding (S)-1-O-acetyl-1,3-hydroxybutane 6 and (R)-1,3-di-O-acetyl-1,3-butanediol 7 with enantiomeric excesses of 91% (E=67.3). Compounds 6 and 7 were easily transformed into the corresponding (S)-3-O-(2-methoxyethoxymethyl)-3-hydroxybutanal 10 and (R)-3-benzyloxybutanal 19, through a protection–deprotection and functional group interchange methodology. Subsequent reaction of 10 and 19 with 3-(methoxycarbonylpropionylmethylene)triphenylphosphorane afforded methyl (E,S)-8-O-(2-methoxyethoxymethyl)-4-oxo-5-nonenoate 12 and (E,R)-8-benzyloxy-4-oxo-5-nonenoate 20. The alkenes 19 and 20 were then catalytically hydrogenated to the corresponding saturated esters 13 and 21. Treatment of 13 and 21 with 1,2-ethanedithiol/F₃B·OEt₂ afforded dithioketals 14 and 22, which were respectively reduced to (S)-1,8-dihydroxy-4-nonanone ethylidenedithioketal 15 and (R)-8-O-benzyl-1,8-dihydroxy-4-nonanone ethylidenedithioketal 23. Finally, deprotection of 15 by catalytic hydrogenation under acidic conditions gave the expected (5S,7S)-(−)-7-methyl-1,6-dioxaspiro[4.5]decane 1. The (5R,7R)-(+)-1 enantiomer was analogously prepared from 23. Both compounds were formed by this procedure with an e.e. of 91%.     

Enantiomerically enriched cyclopropene derivatives: versatile building blocks in asymmetric synthesis

Enantiomerically enriched cyclopropene derivatives, the smallest possible unsaturated carbocycles, are of great synthetic interest since they serve as versatile reactive building blocks. Their reactivity results from the relief of the ring strain in the small molecule. They can be transformed into a wide variety of complex chiral structures and a special emphasis will be directed towards the preparation of enantiomerically enriched methylene- and alkylidenecyclopropane derivatives. The ready availability of a wide range of these chiral entities now provides an excellent opportunity to discover new and unique transformations that can further enrich mainstream synthetic methodology.     

A renaissance of color: New structures and building blocks for organic electronics

Natural dyes and pigments like indigo and its derivatives valued for their bright colors and photochemical stability has been used since antiquity. Recently, the need for better performing materials in the organic electronics field has inspired a resurgence of these historical molecules and their subsequent transformation into new families of π‐conjugated building blocks used to construct new (macro)molecular semiconductors. This Highlight will explore the renaissance of notable building blocks including diketopyrrolopyrrole, (iso)indigo, benzodipyrrolidone, and benzodifuranone, as well as nonfullerene acceptor structures 9,9′‐bifluorenylidene and quinacridone. In addition, as the organic electronics field continues to evolve, the design of molecules with precise structure and function embodies a new paradigm for the next generation of materials. Representative examples will be described that embrace this new model and point the direction for advanced technologies. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Oligosilsesquioxanes as versatile building blocks for the preparation of self-assembled thin films

A self-assembly approach to the preparation of nanocomposite siliceous thin films by using oligosilsesquioxanes as building blocks is presented. Poly(styrene-4-sulfonate), PSS, and octa(3-aminopropyl)silsesquioxane, NSi8, were layer-by-layer (LbL) assembled onto planar substrates and polystyrene (PS) particles, thus forming composite multilayers. We have clarified the binding properties of NSi8 to PSS by examining the pH influence on film buildup by microelectrophoresis (zeta-potential) and quartz crystal microgravimetry (QCM). The regular growth of PSS/NSi8 multilayers on planar supports was confirmed by surface plasmon resonance (SPR) spectroscopy and QCM. By applying the LbL coating procedure to spherical templates, we prepared compact, microporous hollow silica spheres by calcining PS spheres coated with (poly(allylamine hydrochloride) (PAH)/PSS)(2)/(NSi8/PSS)(n) (n varying from 3 to 12), at 750 degrees C, because of sintering of the octameric clusters (NSi8). Hollow spheres derived from coatings with n = 3 drastically altered in size (relative to the template core), depending on the size of the PS particles used. The novelty of this method for the nanofabrication of siliceous films stems from the use of well-defined and discrete building blocks, such as NSi8, leading to homogeneous organic-silica composite films as well as individual siliceous particles of variable size and shape.     

Systematic preparation of Mo 2 4+ building blocks for supramolecular assemblies

The preparation of additional and useful building blocks for the construction of supramolecular entities with quadruply bonded Mo(2)(4+) units has been explored, and five new mixed-ligand complexes with three types of ligands and various basicities are reported. The ligands used were the DAniF (N,N'-di-p-anisylformamidinate) anion, the acetate anion, and neutral acetonitrile molecules. The formamidinate ligands are the least labile, and the acetonitrile molecules are the most labile. This difference as well as a relatively strong trans directing influence by the formamidinate anions in ligand substitution reactions allows designed synthesis of various mixed-ligand building blocks, including rare pairs of cis and trans isomers. The new compounds are cis-Mo(2)(DAniF)(2)(O(2)CCH(3))(2) (1), trans-Mo(2)(DAniF)(2)(O(2)CCH(3))(2) (2), trans-[Mo(2)(DAniF)(2)(O(2)CCH(3))(CH(3)CN(eq)())(2)]BF(4) (3), trans-[Mo(2)(DAniF)(2)(CH(3)CN(eq)())(4)](BF(4))(2) (4), and [Mo(2)(O(2)CH(3))(CH(3)CN(eq)())(6)(CH(3)CN(ax)())](BF(4))(3) (5), where eq and ax designate equatorial and axial ligands, respectively. A comparison with some previously synthesized complexes is given along with a discussion of the overall reactivity of all compounds.     

A simple, two-step, site-specific preparation of fluorinated naphthalene and phenanthrene derivatives from fluorobromo-substituted alkenes

A facile two-step procedure for the site-specific preparation of fluorinated naphthalene and phenanthrene derivatives is described. The Sonogashira reaction of bromofluoro-substituted alkenes with terminal alkynes, followed by base-catalyzed cyclization in refluxing N-methyl-2-pyrrolidinone (NMP), affords the corresponding fluorinated naphthalene and phenanthrene derivatives in good yields.     

Nonbenzenoid aromatic isocyanides: New coordination building blocks for organometallic and surface chemistry

This review is focused on the emerging chemistry of nonbenzenoid aromatic isocyanides, a relatively new family of aryl isocyanide molecules. Two types of systems are discussed: (1) isocyanoazulenes, for which five archetypal isomeric structures may be envisioned, and (2) η⁵-stabilized isocyanocyclopentadienides. So far, the latter are represented by isocyanoferrocene, 1,1′-diisocyanoferrocene, and isocyanocymantrene. In addition, the synthesis and chemistry of the linear 2,6-diisocyanoazulene motif, including regioselective installation and complexation of its –NC termini with controlled orientation of the azulenic dipole, are described. Self-assembly of nonbenzenoid aryl isocyanides and diisocyanides on gold(1 1 1) surfaces is reviewed as well.     

New chiral building blocks from tetrabromocyclopropene and furan

The cyclocondensation of tetrabromocyclopropene and furan leads directly to a halogenated oxabicyclo[3.2.1]octadiene derivative. Over the past several years, we have utilized these compounds as intermediates for natural product synthesis. Herein, we describe the preparation of nonracemic dibromoenone building blocks from the racemic cycloadduct. Conversion of the adduct to a mixture of tartrate-derived ketals followed by separation of the diastereomers and hydrolysis allows for the formation of novel chiral synthons with either absolute configuration.