Tandem carbocupration/oxygenation of terminal alkynes

[chemical reaction: see text]. A direct and general synthesis of alpha-branched aldehydes and their enol derivatives is described. Carbocupration of terminal alkynes and subsequent oxygenation with lithium tert-butyl peroxide generates a metallo-enolate. Trapping with various electrophiles provides alpha-branched aldehydes or stereo-defined trisubstituted enol esters or silyl ethers. The tandem carbocupration/oxygenation tolerates alkyl and silyl ethers, esters, and tertiary amines. The reaction is effective with organocopper complexes derived from primary, secondary, and tertiary Grignard reagents and from n-butyllithium.     

Oxathiazinone Dioxides—A New Group of Sweetening Agents

1,2,3-0xathiazin-4(3H)-one 2,2-dioxides bearing lower alkyl substituents on C-5 and C-6 represent potential sweeteners. They are formed from chloro- or fluorosulfonyl isocyanate and acetylenes, ketones, β-diketones, β-oxo carboxylic esters, or benzyl vinyl ethers via N-halosulfonyl β-oxo carboxamides as common intermediates.     

Steroids and sex hormones. Part 262. The radical induced stannane reduction of selenoesters and selenocarbonates: A new method for the degradation of carboxylic acids to nor-alkanes and for desoxygenation of alcohols to alkanes

Esters of carboselenoic acids, formed from carboxylic acids by conventional methods, undergo reaction with tributyltin hydride in inert aromatic solvents, either by heating to give the corresponding aldehyde or the corresponding alkane depending on reaction temperature and the structure of the parent carboxylic acid, or by ultraviolet irradiation at ambient temperature when the aldehyde is formed predominantly in high yield. In the case of esters of α, β-unsaturated carboselenoic acids the thermal reaction leads only to the corresponding aldehyde. The above stannane reduction can also be applied to selenocarbonates of primary and secondary alcohols (prepared from the corresponding chloroformates), to give the alkane, the parent alcohol and the corresponding formate, in relative amounts depending on the reaction temperature. These reactions thus constitute preparatively useful and high-yield degradation methods compatible with the presence of many other functional groups.     

«Push-Pull»-Acetylene als Hilfsmittel zur Synthese von Amiden

Amide Synthesis by Means of ‘Push-Pull’-Acetylenes ‘Push-Pull’-acetylenes react easily with carbon acids, Addition of amines to the crude reaction mixture gives amides in an excellent yield by a simple one-pot procedure. Because of the high selectivity of the acetylenes 1 towards carboxylic functions and of the high selectivity of the enol esters 4 towards amine functions, ‘push-pull’-acetylenes could be excellent reagents for peptide synthesis.     

A rapid,simple, and mild procedure for alkylation of phenols,alcohols, amides and acids

A general, rapid method is described for alkylation of phenols and alcohols to give ethers, for amides to give N-substituted amides, and for acids to give esters. Differences in optimum reaction times suggest that where two or more such groups as phenol, alcohol, amide, and acid occur in the same molecule, differential alkylation could be effected with suitable substrates. Alkylation with primary alkyl halides was very effective but secondary halides showed evidence for competitive dehydrohalogenation before alkylation was complete and tertiary halides were rapidly dehydrohalogenated with no formation of alkylated derivatives. The method has been applied successfully to N,O-alkylation of peptides for mass spectrometric sequence determination. C-Methylation of peptidic amino-acid residues was observed only on carbon α to a carboxylic ester.     

Mechanism of silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids

Silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids were investigated with the aid of density functional theory calculations. The reaction mechanism starts with a carboxylate complex of silver or copper. Decarboxylation occurs via ejecting CO(2) from the carboxylate complex followed by protodemetallation with an aryl carboxylic acid molecule to regenerate the starting complex. Our results indicated that the primary factor to affect the overall reaction barriers is the ortho steric destabilization effect on the starting carboxylate complexes for most cases. Certain ortho substituents that are capable of coordinating with the catalyst metal center without causing significant ring strain stabilize the decarboxylation transition states and reduce the overall reaction barriers. However, the coordination effect is found to be the secondary factor when compared with the ortho effect.     

Radical-mediated carboxylation of alkyl iodides with [11C]carbon monoxide in solvent mixtures

[reaction: see text] [carboxyl-(11)C]Carboxylic acids were prepared from alkyl iodides via photoinitiated radical reactions using 10(-)(8) mol of [(11)C]carbon monoxide in binary and ternary homogeneous solvent mixtures. Short- (isobutyric), medium-, and long-chain saturated fatty acids (heptadecanoic) were labeled with isolated decay-corrected radiochemical yields ranging from 55% to 70% in 5-7-min reactions. The conversion of [(11)C]carbon monoxide to products reached 80-90%. To obtain good yields in the reactions performed in water-acetonitrile and water-THF mixtures, the addition of tetrabutylammonium hydroxide or potassium hydroxide was essential. The carboxylation was efficient for primary and secondary alkyl iodides. The carboxylation of tertiary iodides was feasible for 1-iodoadamantane but not for tert-butyl iodide. The dependence of the radiochemical yields on reaction time, photoirradiation conditions, and organic and inorganic additives was studied. The method provides a one-step route to [carboxyl-(11)C]carboxylic acids; traditional methods, in contrast, would require several steps. For example, using the devised reaction conditions, 3.19 GBq of purified [1-(11)C]1,10-decanedicarboxylic acid (specific radioactivity 188 GBq/mumol) was obtained within 35 min of the end of 10 muAh bombardment. (1-(13)C)4-Phenylbutyric acid was synthesized using ((13)C)carbon monoxide for identifying the labeling position with (1)H and (13)C NMR.     

Porphyrins with exocyclic rings. Part 21: Influence of pyrrolic and carbocyclic ring alkyl substituents on the synthesis of porphyrins bearing six-membered exocyclic rings

A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives.     

A Simple Convenient Method for the Conversion of Primary Alcohols Into Carboxylic Acids Using Nabro3-HBr/CCl4/T-BuOH System

Reaction of primary alcohols with sodium bromate-hydro-bromic acid system in the presence of excess tert-butyl alcohol gives the corresponding carboxylic acids in moderate to good yields.     

Coupling of Solvolysis and C?C Linkage: A Promising Synthetic Route to Functionalized Carboxylic Acids,Aldehydes, and Ketones

Numerous additions of carbocations to chloroolefins or acetylenes can be coupled with a solvolysis step when performed in a suitable acid; the products are variously substituted carboxylic acids, aldehydes, and ketones. Factors determining the success of these syntheses are the stability of the intermediate carbocations and suppression of the competing addition of protons to the unsaturated reaction component. Under the conditions of the Tscherniac-Einhorn reaction, amidomethylation of chloroolefins and acetylenes, i.e. the introduction of acylaminomethyl groups, is shown not to involve a trigonal α-chloro carbocation or a linear vinyl cation, but instead to proceed via a cyclic oxazinium ion intermediate.     

o-Hydroxyarylphosphines and diphosphines: metallation-rearrangement versus P---O reduction of o-halogenoaryloxyphosphines by sodium

o-Bromo- and o-chloroaryloxyphosphines 1 may react with sodium in two competing ways: (i) metal halogen exchange followed by rapid intramolecular 1,3-rearrangement to give sodium o-hydroxylato-arylphosphines 2, later converted to their OSiMe₃ derivatives 3, and (ii) reductive cleavage of the P---O bond to give diphosphines 4 or phosphides. The o-metallation is preferred with the more reactive bromides and bulky phosphino substituents or screened P---O bonds by substituents at 6-position. The reduction is favoured in the case of the less reactive aryl chlorides, small alkyl and flat phenyl substituents at phosphorus. Mixtures of meso- and rac-diphosphines are formed from asymmetric derivatives ArOPRR′. The meso-isomer of 1,2-di(tert-butyl)-1,2-diphenyldiphosphine is preferred.     

Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, alpha-ketocarboxylic acids, and methyl ketones

An efficient divergent pathway for the selective and quantitative solid-phase conversion of aromatic acetylenes to the corresponding carboxylic acids, alpha-keto-carboxylic acids, and methyl ketones is presented. A range of aromatic trimethylsilyl-protected acetylene building blocks was synthesized in excellent yields using a Sonogashira cross-coupling protocol and used in solid-phase synthesis on PEGA resin. Dependent on the selection of conditions, the same solid-supported alkyne could be quantitatively converted to an aromatic carboxylic acid, an aromatic alpha-ketocarboxylic acid, or an aromatic methyl ketone. The conversion to carboxylic acid involved an OsO4/NaIO4/HMTA-mediated oxidative cleavage of the silyl-deprotected alkyne to provide the aromatic carboxylate in excellent yield. The alpha-ketocarboxylic acids were obtained by direct treatment of the trimethylsilyl-protected alkyne with OsO4/NMO/HMTA, while the ketones were obtained by simple acid-mediated hydration of the alkyne using aqueous TFA. In general, all products were obtained in excellent purities, typically above 90%. In addition, it was shown that the alkyne-containing building blocks could easily be incorporated into resin-bound peptides and after chemoselective conversion of the alkyne the new functional groups could be used for further derivatization into peptidomimetic compounds.     

Lewis and mediated α-alkylation of ketones using SN1 reactive alkylating agents

Alkylation of ketones via silyl enol ethers is possible using aryl activated secondary alkyl halides or thio ketals. In case of prenyl halides the ratio fo primary to tertiary alkylation is governed by steric factors and by the nature of the Lewis acid.     

Chemical and spectroscopic methods for investigating polymer degradation and stabilization: Oxidative degradation of a hydrogenated nitrile rubber

The oxidation of a hydrogenated butadiene-acrylonitrile (2:1 mole ratio) rubber has been examined by infrared (IR) spectroscopy and the use of γ-initiation to give a controlled initiation step. The resolution and sensitivity of the IR technique was enhanced by the use of chemical derivatization in which carboxylic acids were measured as acid fluorides, hydroperoxides as nitrates and alcohols as nitrites. In all of these compounds, their spectra are sensitive to the precise substituents (primary, secondary or tertiary). Oxidation produced hydroperoxides from both tert. H-C-C=N and sec. H-C-H groups (≈︁1:1.1 mole ratio) as well as chain-end carboxylic acids [-CH₂-C(=O)OH]. From a comparison with measurements of peroxyl radicals produced at low temperature, average kinetic chain lengths for the various oxidation products were estimated and compared with these from other ethylene copolymers.     

Scandium Trifluoromethanesulfonate as an Extremely Active Lewis Acid Catalyst in Acylation of Alcohols with Acid Anhydrides and Mixed Anhydrides

Scandium trifluoromethanesulfonate (triflate), which is commercially available, is a practical and useful Lewis acid catalyst for acylation of alcohols with acid anhydrides or the esterification of alcohols by carboxylic acids in the presence of p-nitrobenzoic anhydrides. The remarkably high catalytic activity of scandium triflate can be used for assisting the acylation by acid anhydrides of not only primary alcohols but also sterically-hindered secondary or tertiary alcohols. The method presented is especially effective for selective macrolactonization of omega-hydroxy carboxylic acids.     

Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.     

季铵盐参与的直接化学选择性O-和N-烷基化反应

将羧酸或胺类化合物与季铵盐进行简单的混合加热,便可直接得到O-或N-烷基化产物。季铵盐中烷基的转移具有较好的选择性,其优先顺序为：苄基〉伯烷基〉仲烷基。     

Synthesis of naturally occurring acetylenes via an alkylidene carbenoid rearrangement

Naturally occurring mosquito larvicidal acetylenes 1 and 2, and analogues 3 and 4, each containing either a 1,3-butadiynyl or a 1,3,5-hexatriynyl moiety, are synthesized via a Fritsch-Buttenberg-Wiechell rearrangement. The alkylidene carbenoid intermediate results from lithium-halogen exchange of a suitable dibromoolefin precursor, and the rearrangement is accomplished under mild conditions. Synthesis of the dibromoolefin precursors to acetylenes 1-4 is easily achieved in three steps from commercially available carboxylic acids or aldehydes, making this procedure a viable alternative to conventional methods for the synthesis of naturally occurring acetylenes.     

Solid-phase synthesis of substituted 3-amino-3′-carboxy-tetrahydrocarbazoles

Two related solid-phase synthesis routes have been developed allowing the synthesis of 3-amino-3′-carboxy substituted tetrahydrocarbazole derivatives. Diversity can be introduced at the amino and carboxy functionalities and at the nitrogen and the aromatic ring of the tetrahydrocarbazole moiety. Both routes rely on Fmoc-protected 1-amino-4-oxocyclohexanone carboxylic acid as central core element. Derivatization of the carboxy function is achieved with amines, derivatization of the amino functionality is possible by reaction with alkyl halides, isocyanates, activated alcohols, sulfonic acid chlorides or carboxylic acids. The tetrahydrocarbazole scaffold is generated by Fischer indole cyclization with phenyl hydrazine derivatives, thereby introducing diversity in the aromatic moiety. N-Alkylation at the indole nitrogen with alkyl halides delivers N-substituted derivatives.     

Esterification and Selective Esterification in the Presence of TiCl4

A series of carboxylic acids was esterified to the corresponding esters with TiCl_4 as catalyst at room temperature,in high yields.This catalyst was highly effective for the selective esterification of primary alcohols with carboxylic acids,in the presence of secondary alcohols,and for the selective esterification of saturated acid with alcohol in the presence of conjugated acid or aromatic acid.On account of the high yield,high chemoselectivity,mild condition,and being free of other dehydrants,this is an efficient method.