Acid chlorides oxalyl chloride/DMSO

Scheme 14.6 Total synthesis of cytochalasin O (1160), starting from Diels-Alder product 1155. Reagents and conditions a) OSO4, pyridine, —20°C, 69% b) 2,2-dunethoxypropane, p-toluenesulfonic acid, CHQ3, rt c) LDA, PhSeCl, THF, —35°C, 52% over two steps d) NaOH, MeOH (aq.), rt e) H2O2 (aq.), pyridine, CH2CI2, rt, 88% over two steps f) NaBIl, CeCls H2O, MeOH, 10°C, 98% g) Ac O, NEts, DMAP, CH2CI2, rt, 81% h) p-toluenesulfonic acid, MeOH, rt, 74% i) oxalyl chloride, DMSO, NEtj, CH2CI2, -60 C to rt, 66% j) HCl (aq.), MeOH, reflux, 78%...

When there is no diluent, organic acid chlorides and metal halides react very violently with DMSO. This goes for acetyl chloride, benzenesulphonyl (C6H5SO2CI), cyanuryl chloride, phosphorus and phosphoryl trichlorides, tetrachlorosilane, sulphur, thionyl, and sulphuryl chlorides. With oxalyl chloride, the reaction is explosive at ambient temperature, but can be controlled at -60°C in a solution with dichloromethane. The dangerous reactions are thought to be... 

In absence of diluent or other effective control of reaction rate, the sulfoxide reacts violently or explosively with the following acetyl chloride, benzenesul-fonyl chloride, cyanuric chloride, phosphorus trichloride, phosphoryl chloride, tetrachlorosilane, sulfur dichloride, disulfur dichloride, sulfuryl chloride or thionyl chloride [1], These violent reactions are explained in terms of exothermic polymerisation of formaldehyde produced under a variety of conditions by interaction of the sulfoxide with reactive halides, acidic or basic reagents [2], Oxalyl chloride reacts explosively with DMSO at ambient temperature, but controllably in dichloromethane at -60°C [3]. 

There are several methods reported in the literature for transforming vicinal diols into ct-diketones while avoiding the risk of C-C bond cleavage.26 Examples include the standard Swem conditions (dimethyl sulfoxide and oxalyl chloride followed by triethylamine), or the use of DMSO activated by acetic anhydride, pyridine-sulfur trioxide complex, or dicyclohexylcarbodiimide (Mq/J-att oxidation). Diones are also obtained by treatment with benzalacetone as a hydride acceptor in the presence of catalytic amounts of tris(triphenylphosphine)ruthenium dichlonde [(PPh RuCFl.27 Recent developments include the use of w-iodoxyben/.oic acid28 or the oxoammonium salt of 4-acctamidoletramethylpipcridine-1-oxyl and y -toluencNulfonic acid.29... 

The decomposition of acid-sensitive substrates during Swern oxidations can also be explained by the presence of adventitious hydrogen chloride. This can be avoided by the use of freshly distilled oxalyl chloride and carefully dried DMSO.174... 

During Swern oxidations, adventitious HC1 may be present either due to the use of impure oxalyl chloride, or due to the hydrolysis of some chlorine-containing chemical, caused by employing wet DMSO. Adventitious HC1 may cause acid-induced side reactions on sensitive substrates.174,246... 

A variety of methods have been described to solve the task in solution.16 Common oxidative agents for this transformation include various heavy-metal reagents such as chromium-or ruthenium-based oxides, pyri-dine-S03, and dimethylsulfoxide (DMSO) in combination with acetic anhydride, carbodiimide, or oxalyl chloride for activation. One of the most prominent methods for the reliable conversion of sensitive compounds is the Dess-Martin reagent or its nonacetylated equivalent, 1-hydroxy-(17/)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX). 

One example is Swern oxidation, which uses oxalyl chloride and DMSO and is particularly suitable for the selective oxidation of alcohols to aldehydes or ketones. The disadvantages of this oxidation method are the need for low temperatures, the smell of the dimethyl sulfide formed and the possible oxidation of other heteroatoms. Dess-Martin periodinane (DMP, 5) or iodoxybenzoic acid (IBX, 6) are also common oxidizing agents. The main advantage of these two methods is the short reaction time at room temperature. However, typical problems are the low solubility of IBX and the formation of byproducts. In this context, Finney et al. have reported an interesting procedure avoiding these problems by a variation of the temperature IBX is sufficiently soluble in solvents such as ethyl acetate or dichloromethane at elevated temperatures, whereas it is insoluble in these solvents at room temperature. Because of this, the remaining IBX as well as the IBX-derived byproducts can be separated from the reaction mixture by simple filtration. These reisolated IBX byproducts can then be reoxidized and reused. 

Swem oxidation A mild oxidation, using DMSO and oxalyl chloride, that can oxidize primary alcohols to aldehydes and secondary alcohols to ketones, (p. 465) tosylate ester An ester of an alcohol with para-toluenesulfonic acid. Like halide ions, the tosylate anion is an excellent leaving group, (p. 469)... 

TBDMS = tert-butyidimethylsilyl TMS = trimethylsilyl MCPBA = metachloroperbenzoic acid DMSO s dimethyisuifoxide (COCI)o = oxalyl chloride Pb(0A 4 = lead tetraacetate... 

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