In situ generation

Internal alkynes are oxidized to acytoins by thalliuin(III) in acidic solution (A. McKil-lop, 1973 G.W. Rotermund, 1975) or to 1,2-diketones by permanganate or by in situ generated ruthenium tetroxide (D.G. Lee, 1969, 1973 H. Gopal, 1971). Terminal alkynes undergo oxidative degradation to carboxylic acids with loss of the terminal carbon atom with these oxidants. 

While both 2- and 3-vinylindole have been synthesized and characterized[l,2], they arc quite reactive and susceptible to polymerization. This is also true for simple l-alkyl derivatives which readily undergo acid-catalysed dimerization and polymerization[3]. For this reason, except for certain cases where in situ generation of the vinylindoles is practical, most synthetic applications of vinylindoles involve derivatives stabilized by EW-nitrogen substituents[4]. 

The single-step -duoroaruline [31-40-4] process based on duorodeoxygenation of nitrobenzene (via in situ generation of /V-phenylhydroxyl amine) in anhydrous hydrogen duoride (94—96) has not been commercialized primarily due to concurrent formation of aniline, as well as limited catalyst life. The potential attractiveness of this approach is evidenced by numerous patents (97—101). Concurrent interest has been shown in the two-step process based on /V-phenylhydroxylamine (HF-Bamberger reaction) (102—104). 

PolysuWde Process. One modification to the kraft process being appHed commercially is the polysulfide process (38). Under alkaline conditions and relatively low temperature (100—120°C), polysulfides oxidize the active end group of the polysaccharide polymer to an alkaH-stable aldonic acid. This reaction, known for many years (39), was not produced on a commercial scale until the development of an efficient method for in situ generation of the polysulfide in kraft white Hquor. 

Although no acyl hypochlorites [RCO2CI] have been isolated in pure form, they have been characterized in solution and employed as reactants via in situ generation from CI2O or HOCl and carboxyUc acids, or from CI2 and silver salts of carboxyUc acids (246,247). Perfluoroacyl hypochlorites have also been prepared (248). 

TCCA can also be prepared by reaction of performed or in situ generated HOCl with CA slurry (23). Chlorine monoxide can also be used to prepare TCCA from finely powdered CA (24). 

This series is punctuated by several unusual synthons, one the reaction of tropone (567) with aniline to give (568). The cyclization of (569) with sodium hydroxide gave (570) (67AHC(8)277, 69M602). The reaction of in situ generated benzyne with the nitrone (571) produced (572) (67AHC(8)277). 

NaH, THF, BnBr, Bu4N I, 20°, 3 h, 100%. This method was used to protect a hindered hydroxyl group. Increased reactivity is achieved by the in situ generation of benzyl iodide. ... 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

Treatment of A -benzyltnfluoroacetimidoyl chloride with triethylamine in toluene at room temperature leads to in situ generation of trifluoroacetonitrile ben-zylide [4J] (equation 43), which reacts with methyl acrylate to form cycloadducts [43] (equation 44) Although the kinetic ratio of products favors the cis adduct (3 1), thermodynamic equilibration leads to an excess of the trans isomer (7 1). 

Silver(I) triflate is widely applied to the preparation of various derivatives of triflic acid, both covalent esters [66] and ionic salts For example, it can be used for the in situ generation of iodine([) triflate, a very effective lodinatmg reagent for aromatic and heteroaromatic compounds [130] (equations 65 and 66)... 

The [SaN]" cation was first obtained in low yield in 1978 by the oxidation of S7NH with SbCls. The reaction of in situ generated [SN]" salts with sulfur (Scheme 5.3) or the reduction of the [ClSNSCl] cation with anhydrous tin(II) chloride in SO2 or CH2CI2 can be used to prepare [S2N] salts. The best large scale synthesis involves the reaction of AsFs with a mixture of S4N4 and sulfur in the presence of a trace amount of bromine (as a catalyst) (Eq. 5.10). ... 

The in situ generation of the carbon dioxide adduct of an indole provides sufficient protection and activation of an indole for metalation at C-2 with r-butyl-lithium. The lithium reagent can be quenched with an electrophile, and quenching of the reaction with water releases the carbon dioxide. ... 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

Advantages of the in situ generation include ease of isolation and ee upgrades of crystalline products. Table 1.6.1 shows the beneficial effect of performing the AE reaction under catalytic conditions as well as in situ derivatization. 

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. Examples are shown later. 

An interesting application of the Paal thiophene synthesis was documented for the synthesis of a polystyrene-oligothiophene-polystyrene copolymer. In the Stetter reaction of aldehyde 13 and P-dimethylaminoketone 14, in situ generation of the a,p-unsaturated ketone preceded nucleophilic 1,4-conjugate addition by the acyl anion... 

It has been shown that TMSI is capable of mediating the reaction at room temperature. The classical three component coupling was carried out using aldehyde 82 and ketoester 83 with ammonium acetate in acetonitrile at room temperature with in situ generated TMSI. This gave a 73-80% yield of 1,4-dihydropyridines 84 in 6-8 h. The best results were obtained with 1 equivalent of TMSCl and 1 equivalent of Nal. 

A related route to the protoberberine skeleton was reported by Lete, in which substrate 54 underwent Bischler-Napieralski reaction followed by intramolecular alkylation of an in situ generated alkyl chloride to afford 55. °... 

These results are in agreement with Charette s findings regarding the reactivity of in-situ generated iodomethylzinc alkoxides (Scheme 3.29) [60]. The significance of this phenomenon will become important in the design of asymmetric catalysts. 

A. Cyclohexanol from Cyclohexene In Situ Generation of Diborane in Diglyme... 

In the following procedure, use is made of the basic character of epoxides. In the presence of phosphonium salts, ethylene oxide removes hydrogen halide and the alkylidenetriphenylphosphorane is produced. If a suitable carbonyl compound is present in the reaction mixture, its reaction with the in situ generated phosphorane proceeds readily to give the Wittig product. 

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