Oxalyl chloride activator

Protecting groups that are cleaved by an oxidant, like p-methoxyben-zyl201 and dimethoxybenzyl202 ethers or p-methoxybenzylidene203 and dimethoxybenzylidene204 acetals, resist the action of oxalyl chloride-activated DMSO. 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

Swern also found that oxalyl chloride activates DMSO for the oxidation of alcohols. ... 

Mild oxidation of primary and secondary alcohols, promoted by oxalyl chloride activation of dimethyl sulfoxide, evidently involving the dimethyl alkoxysulfonium salts. Upon the addition of base, the intermediates rearrange intramolecularly to generate aldehydes or ketones, respectively ... 

A series of substituted ortho-phthalaldehydes has been prepared under mild conditions in respectable yields by oxidation of the corresponding dimethanols using oxalyl chloride activated DMSO [1343]. 

Reaction of a nucleoside with thiophosphoryl chloride, followed by base-promoted cyclization, provides a direct synthesis of nucleoside-3, 5 -cycllc phosphorothioates (both epimers at phosphorus). 125 Treatment of cyclic AMP with dlphenylphosphoiyl chloride produces the mixed anhydride, predominantly of Rp configuration (62), due to the greater basicity of the axial oxygen in the cAMP. The anhydride reacted with dimethylamine with inversion to give the cyclic phosphoramidate.i26 Activation of cAMP with POCI3 in (MeOlaPO, followed by treatment with an amine, also gave predominantly the Sp-phosphoramidate (63),127 and in the case of a protected cAMP, oxalyl chloride activation achieved a similar result. 128 The hydrolysis of... 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

In order to enable the dimethyl sulfoxide 3 to oxidize the alcohol substrate effectively, it has to be converted into an reactive agent. This is carried out by treatment with oxalyl chloride 4, hence leading to sulfonium ions 5 or 6 as the active species ... 

The ionic species 5, as well as 6, represent the so-called activated dimethyl sulfoxide. Variants using reagents other than oxalyl chloride for the activation of DMSO are known. In the reaction with an alcohol 1, species 5, as well as 6, leads to the formation of a sulfonium salt 7 ... 

The Vilsmeier-Haack type adduct, formed by the reaction of oxalyl chloride with DMF can be also be employed for the activation of carboxylic acids, as shown in Fig. 8 [200]. 

A convenient modification of the Gassman oxindole synthesis was reported using ethyl (methylsulfinyl)acetate (101) activated by oxalyl chloride to generate the same chlorosulfonium salt 102 normally generated from ethyl (methylthio)acetate 100 and elemental chlorine <96TL4631>. Thus, treatment of the sulfoxide 101 with oxalyl chloride, followed by the addition of the desired aniline, triethylamine, and finally acid cyclization of 103 affords the oxindoles 104. This procedure is particularly convenient for reactions carried out on smaller scales and for anilines that ate susceptible to electrophiUc halogenation. 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

In 2001, Knaack and co-workers56 reported an application of the INADEQUATE experiment in the course of synthesizing and characterizing a biologically active 2-[l-(4-chlorobenzyl)-lH-indol-3-yl]-2-oxo-N-pyri-din-4-yl acetamide (6). Treatment of l-(4-chlorobenzyl)-lH-indole with oxalyl chloride afforded the corresponding oxoacetyl chloride that was finally subjected to aminolysis with 4-aminopyridine to afford the final product of the reaction scheme, 6. Although the NMR data supported the N-benzyl structure, a 1,1-ADEQUATE spectrum was acquired to provide additional confirmation of the structure of 6. 

As second example for the scale-up of solid-phase reactions directly on solid support, we chose an arylsulfonamido-substituted hydroxamic acid derivative stemming from the matrix metalloproteinase inhibitor library (MMP) of our research colleagues (Breitenstein et al. 2001). In this case, there was already a solution-phase synthesis available for comparison (see Scheme 4). The synthesis starts with the inline formation of a benzaldehyde 18 with the glycine methyl ester, which is then reduced to the benzylamine 20 using sodium borohydride in methanol/ THF (2 1). The sulfonamide formation is carried out in dioxane/H20 (2 1) with triethylamine as the base and after neutralisation and evaporation the product 21 can be crystallised from tert. butylmethyl ether. After deprotection with LiOH, the acid is activated by treatment with oxalyl chloride and finally converted into the hyroxamic acid 23 in 33.7% yield overall. 

Oxidation of alcohols.1 This phosphate is apparently as efficient as oxalyl chloride for activation of DMSO for oxidation, and the derived reagent is less prone to give chlorine-containing byproducts. The reactions are rapid at 20° or below, and yields are generally 75-95%. 

Antibacterial activity is retained when the relatively complex amide side chains are replaced by a simple heterocycle amidine. The required reagent (7-2) is prepared by reaction of azepine formamide (7-1) with oxalyl chloride. Condensation of the product with 6-APA (2-4) leads to the formation of the amidine and thus amdinocillin (7-3) [11]. 

Derived reagents. Mancuso and Swern2 have reviewed activated dimethyl sulfoxide reagents (100 references). Activation of DMSO with cither trifhioroacelic anhydride (7, 136) or oxalyl chloride (8, 200) provides the most generally useful... 

The dimethyl sulfoxide (Me2SO)-dicyclohexyl carbodiimide (DCC) method described by Pfitzner and Moffatt24 opened a route to keto derivatives of aldopentosylpyrimidines,2,25 as well as to many keto derivatives of hexosyl-purines3,7,26-31 and -pyrimidines.30,32,33 An alternative proposed by Swern and coworkers,34 requiring the presence of oxalyl chloride as an activating agent, has been used to prepare 4-keto-lyxo-hexose C-nucleosides.13... 

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