A mixed anhydride approach to the preparation of sulfinate esters and allylic sulfones: Trimethylacetic p-toluenesulfinic anhydride

A reagent combination of toluenesulfinic acid and trimethylacetyl chloride affords a putative trimethylacetic p-toluenesulfinic anhydride. This reagent has been used to prepare a series of sulfinate esters from primary and secondary alcohols. In addition, the reagent was used to convert Baylis-Hillman substrates into allylic sulfones. Attempts to use the reagent to convert amines to sulfinamides were unsuccessful. In contrast, the use of 2-pyrrolidinone afforded N-p-toluenesulfinyl pyrrolidinone in 64% yield. The use of a chiral 4-benzyl-1,3-oxazolidinone or 4-benzyl-1,3-oxazolidine-2-thione led to the isolation of S-p-tolyl p-toluenethiosulfonate.     

The synthesis of fluorinated α-pyrans via fluorinated vinylcopper reagents

Fluorinated vinylcopper reagents were prepared in situ via reaction of fluorinated vinylbromides or iodides with cadmium or zinc powder followed by metathesis with Cu(I)Br. Hexafluoro-2-butyne was then added to the solution of the F-vinylcopper reagent which resulted in a stereospecific syn addition of the F-vinylcopper reagent to the alkyne to provide in situ the corresponding dienylcopper reagent. Subsequent acylation of the dienylcopper reagent gave a dienylketone, which spontaneously cyclized to the 2H-pyran. This methodology provides a useful one flask route to fluorinated 2H-pyrans.     

Large-scale synthesis of high purity “Phos reagent” useful for oligonucleotide therapeutics

A large-scale, cost-effective, and environmentally clean synthesis of high purity 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (Phos reagent) has been accomplished on a commercial scale. Treatment of PCl₃ with diisopropylamine followed by 3-hydroxylpropionitrile furnished the Phos reagent in excellent yield. The ³¹P NMR of the Phos reagent prepared at large-scale show consistent purities >99% when several key factors are controlled. These controlling factors include sourcing high purity key raw materials, identification and elimination of critical impurities, stability and storage of Phos reagent.     

N-p-chlorophenylcinnamohydroxamic acid: A new reagent for the microgram determination of vanadium(V)

A new reagent, N-p-chlorophenylcinnamohydroxamic acid, for the rapid solvent extraction and spectrophotometric determination of microgram quantities of vanadium(V) is reported. Vanadium(V) is extracted from a chloroform solution of the reagent, N-p-chloro-phenylcinnamohydroxamic acid, with 4–8 M HCl. The bluish violet extract has maximum absorbance at 545 nm. The extract obeys Beer's law at 545 nm, and the sensitivity of the reagent is 0.008 μg V/ml. The complex is stable for several days. The effects of acidity, reagent concentrations, and diverse ions are discussed.     

Polymer-supported thioanisole: a versatile platform for organic synthesis reagents

A new cross-linked polystyrene-supported thioanisole reagent is reported. This reagent incorporates the flexible JandaJel™ cross-linker and can be treated with methyl trifluoromethanesulfonate to form the corresponding sulfonium salt. This salt can in turn be deprotonated to form a polymer-supported sulfur ylide that is able to react with aldehydes and ketones to form epoxides. The thioanisole reagent can also be oxidized to form an insoluble sulfoxide reagent that is useful in Swern oxidation reactions. In these reactions, the polymer-supported thioanisole-based reagents can be recovered, regenerated and reused.     

Preparation and diastereo- and enantioselective trifluorocrotylboration with (Z)-(B)-diisopinocampheyl(4,4,4-trifluorobut-2-en-1-yl)borane

Contrary to the non-fluorinated analogs, the hydroboration of trifluoromethylallene with diisopinocampheylborane provides the corresponding Z-trifluorocrotylborane reagent. Trifluorocrotylboration of a series of aldehydes with this reagent provides the corresponding syn-β-trifluoromethyl homoallyl alcohols in high diastereo- and enantioselectivities.     

Synthesis and Single Crystal Structures of N-Substituted Benzamides and Their Chemoselective Selenation/Reduction Derivatives

A series of N-aryl-N-(2-oxo-2-arylethyl) benzamides and cinnamides has been prepared. The reaction of the benzamides with Woollins’ reagent, a highly efficient chemoselective selenation/reduction reagent, gave the corresponding N-aryl-N-(arylenethyl) benzoselenoamides in good yields. Five representative single crystal X-ray structures are discussed.     

N-Fluoro-(3,5-di-tert-butyl-4-methoxy)benzenesulfonimide (NFBSI): A sterically demanding electrophilic fluorinating reagent for enantioselective fluorination

We disclose here a novel electrophilic fluorinating reagent, N-fluoro-(3,5-di-tert-butyl-4-methoxy)benzenesulfonimide (NFBSI) as a sterically demanding analogue of popular fluorinating reagent, N-fluorobenzenesulfonmide (NFSI). NFBSI improves the enantioselectivity of the products as much as 18% for the cinchona alkaloid-catalyzed enantioselective fluorination of silylenol ether compared to the use of NFSI.     

Trivalent manganese as an oxidimetric reagent

A study of the use of trivalent manganese as an oxidimetric reagent has been made. The manganic ion was stabilised with pyrophosphate. The stability of this reagent over a period of six weeks was established. The reagent may be used in conjunction with barium diphenylamine sulphonate for the titration of ferrous iron even in the presence of 5N hydrochloric acid. It may also be used for the titration of vanadium, nitrite, oxalate, peroxide and arsenite, but the procedures for oxalate and peroxide are unsatisfactory. The redox potential of the reagent was 1.22 volt at 25° C, which was lower than that found for manganic sulphate (ca. 1.4 volt).     

A polystyrene-supported triflating reagent for the synthesis of aryl triflates

An insoluble polystyrene-supported triflating reagent has been prepared by suspension co-polymerization of N-(4-vinylphenyl)trifluoromethanesulphonimide, styrene and the JandaJel^® cross-linker. This reagent, in the presence of triethylamine, allows for the efficient synthesis of aryl triflates from a wide range of phenols in a process that permits the desired product to be isolated from the reaction mixture in essentially pure form via several filtration and concentration operations. Adding to the utility of this reagent is its ability to be easily recovered, regenerated and reused. Both soluble and insoluble bifunctional polymers containing trialkylamine moieties in addition to triflimide groups were also prepared and examined as triflating reagents. Unfortunately these reagents afforded only modest yields of the desired products in representative reactions.     

A visual test paper for extremely strong concentrated acidity with a new synthesized isoindole reagent

A visual test paper by taking common filter paper as solid support for extremely strong concentrated acidity has been developed in this contribution with a new synthesized isoindole compound starting from p-phenylenediamine and the coupled fluorogenic reagent of o-phthaldialdehyde-β-mercaptoethanol. It was very easy for semiquantitative detection of acidity in the range of 0.2-18 M ([H⁺]) in extreme acidic solution based on the color changes of the solution or the visual test paper prepared by immerging filter paper slides into the solution of the new synthesized reagent. Quantitative detection of concentrated strong acids could be successfully constructed through the linear relationship exists between the absorbance of the chromogenic reagent at 510 nm and the acid concentrations.     

Deuterated N-difluoromethylthiophthalimide: A stable,scalable reagent for radical and electrophilic deuteriodifluoromethylthiolations

A new, stable and scalable reagent for deuteriodifluoromethylthiolation (deuterated N-difluoromethylthiophthalimide, PhthSCF₂D) has been developed. This reagent can be applied for the photocatalytic radical deuteriodifluoromethylthiolation of various olefins and aldehydes (30 examples). Meanwhile, it can achieve the electrophilic deuteriodifluoromethylthiolation of a series of electrophilic substrates including electron-rich arenes, aryl/vinylboronicacids, alkynes, amines, thiols and β-ketoesters (22 examples). Some complex molecules can also be applied in both radical and electrophilic deuteriodifluoromethylthiolation using PhthSCF₂D as the reagent.     

Extraction and complexation of Cu(II) with undecanoic acid <Emphasis Type="Italic">N,N</Emphasis>-diethylhydrazide

A new reagent, undecanoic acid N,N-diethylhydrazide, was synthesized, and its pK _a1 was determined. The reagent recovers Cu(II) to 99–100% from solutions whose acidity ranges from pH 6 to 1 M NH₃. Copper(II) is extracted in the form of a neutral complex of the composition Cu(II):reagent = 1:2. The reagent is incorporated in the complex in the deprotonated form. An equation for the extraction of Cu(II) from ammonia solutions was suggested. The extraction isotherm was constructred. Ammonium salts, when present in solution, considerably decrease the degree of copper extraction. The reagent is less efficient extractant of copper than N,N-diethylbenzhydrazide.     

Convenient synthesis of alkyl thioacetate from alkyl halide using a polymer-supported sodium thioacetate

Alkyl halides are efficiently converted to their corresponding S-alkyl thioacetates under mild and nonaqueous conditions, using polymer-supported sodium thioacetate as a new polymeric reagent at room temperature in high yields and purity. The spent polymeric reagent can be removed quantitatively by filtration and pure products can be obtained by evaporation of the solvent. The spent polymeric reagent can be regenerated and reused several times without its activity changing appreciably.     

Reaction of Halothane with sec-butyllithium in the presence of zinc halides—one-pot preparation of chlorodifluorovinylzinc reagent and its derivatization to α-chloro-β,β-difluorostyrene

Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane, reacts with sec-butyllithium in the presence of zinc halides to afford a chlorodifluorovinylzinc reagent. This zinc reagent reacts with aryl halides in the presence of a palladium catalyst to give chlorodifluorostyrene derivatives in moderate to good yields.     

Titanium tetrachloride mediated reductive ring opening of C-aryl pseudoglycals

A facile reductive ring opening of C-aryl pseudoglycals is reported for the first time. The combination of titanium tetrachloride (Lewis acid) and triethylsilane (reducing agent) at −78 °C in dichloromethane is a mild and efficient reagent system for this transformation. The reagent system was successfully tested on various C-aryl pseudoglycal substrates to yield the corresponding ring opened products containing two asymmetric hydroxyls and a cis-double bond.     

Chemical transformations of diazoles in the reactions of carboxylation, N-siloxycarbonylation, and transsilylation

The behavior of 3,5-dimethylpyrazole, 3(5)-methylpyrazole, imidazole and their trimethyl-silyl derivatives in carboxylation, N-siloxycarbonylation, and transsilylation reactions was studied. A new Nsiloxycarbonylation reagent, diazole trimethylsilyl derivative-carbon dioxide, was found. This reagent makes it possible to obtain easily O-silylurethanes starting from primary, secondary amines and hydrazine derivatives, as well as to develop a convenient one pot synthesis method for trimethylsiloxycarbonyldiazoles.     

Chemo- and stereoselectivity in titanium-mediated regioselective ring-opening reaction of epoxides at the more substituted carbon

Chemo- and stereoselectivity in the ring-opening reaction of epoxides with a reagent prepared from allylmagnesium halide and chlorotitanium triphenoxide is described. It has been proven that the allylating reagent can also be used for the reaction of epoxides bearing a tert-butyl ester, amide, or acetal moiety, and that the epoxide cleavage regioselectively takes place at the more substituted carbon in all cases. Interestingly, while the reaction of acyclic 2,2,3-trialkyl epoxides or 3,3-disubstituted 2,3-epoxy alcohol derivatives with the allyltitanium reagent yielded the allylated products as an almost 1:1 diastereomixture, the ring-opening reaction of 2-substituted 2,3-epoxy alcohol derivatives stereospecifically proceeded through the anti pathway. The latter reaction is extremely useful for asymmetric construction of quaternary carbon centers.     

The Vilsmeier reagent: a useful and versatile reagent for the synthesis of 2-azetidinones

(Chloromethylene)dimethylammonium chloride (Vilsmeier reagent), prepared easily from N,N-dimethylformamide and oxalyl chloride or thionyl chloride, works as a versatile acid activator reagent for the direct [2+2] ketene-imine cycloaddition of substituted acetic acid and imines in one-pot synthesis under mild conditions. Monocyclic, spirocyclic and 3-electron-withdrawing group β-lactams were synthesized by this method and optimization of conditions were performed.