Swern conditions

A PDC oxidation, followed by removal of the chromium salts with Florisil , gives a good yield of an unstable aldehyde. Attempted oxidation using Swern conditions met the problem of decomposition of the aldehyde during column chromatography. 

Treatment of the starting alcohol under Swern conditions gave chlorinated products, while chromic acid gave a low yield, and PCC led to a complex separation of the product from chromium-containing residues. An excellent yield of the desired ketone was obtained by using the Taber modification of the Albright-Onodera oxidation. 

After considerable experimentation, it was found that the Parikh-Doering oxidation provides a good and reproducible yield. Under Swern conditions, yields are erratic with substantial quantities of a product, arising from opening of the epoxide by attack of a chloride ion being formed. PCC did not afford a good yield of alcohol. 

A highly unstable aldehyde is obtained under Swern conditions, while PCC, PDC, Jones oxidation and Dess-Martin periodinane lead to decomposition. 

In an enantioselective synthesis of a key intermediate for the preparation of poisons from the skin of tropical frogs, a key oxidation was performed under Swern conditions with 77% yield, while PCC provided a 28% yield and Pfitzner-Moffatt oxidation 73% yield. 

Under normal Swern conditions, as the oxidation of alcohols is quicker than the reaction with epoxides, it is possible to oxidize alcohols with no interference of epoxides in the same molecule.198... 

Primary TMS and TES ethers205 are deprotected and transformed into the corresponding aldehydes under Swern conditions. Other less labile silyl ethers—such as TBS ethers as well as secondary TMS and TES ethers—, remain unaffected. This allows to perform selective oxidations of primary alcohols in the presence of secondary ones by persilylation of poliols by TMS or TES, followed by selective oxidation of the primary silyl ethers to aldehydes under Swern conditions. 

Tertiary amines normally remain unaffected under Swern conditions. 

Primary amides react under Swern conditions, producing the corresponding nitriles213 and minor amounts of iminosulfurans.210 Nonetheless, there is some report depicting the selective oxidation of alcohols in the presence of primary amides.214 Secondary and tertiary amides remain unaffected. 

This is a rare case of methylthiomethylation of a primary alcohol during a Swern oxidation. A primary neopentilic alcohol, quite resistant to reaction, was treated under Swern conditions at the temperature of - 10°C. At this temperature, a substantial decomposition of activated DMSO occurred during the activation of the alcohol, resulting in the formation of H2C=S(+)-Me that produced the generation of the methylthiomethyl ether side compound. 

Ref 75 With PDC or under Swern conditions, the sensitive pyrrole ring is destroyed, while catalytic TPAP provides a 63% yield of the desired ketone. ... 

NaBH4 provides a method to reduce the ester 54 to alcohol 55. The additive LiCl is used to enhance the reactivity of NaBH4 towards esters.10 Alcohol 55 is then oxidized to aldehyde 11 using Swern conditions with (COCl)2 and DMSO (see Chapter 2). 

Oxidation of the alcohol under Swern conditions (see Chapter 2) followed by addition of commercially available ethylmagnesium-bromide provided the secondary alcohol with nearly no stereocontrol (1 1.1 in favor of isomer 12b) in 90 % overall yield. 

Treatment of naphtho[2,l- ][l,5]oxazocine 464 with HF yielded the deprotected alcohol 465 (95%), which was subsequently oxidized under Swern conditions to give the oxo-butyl 1,5-oxazocine 466 (96%). Reaction of the latter with 4-[(.y)-2-methylsulfinylphenyl]piperidine in presence of NaBH4 under standard reductive animation, afforded the oxazocine 467 (72%) (Scheme 93) <2004BMC2653>. 

There are many methods for selectively oxidizing an alcohol to the corresponding aldehyde. Of course you have to think about the stability of your molecule when you decide which procedure to choose, but ecological and economic aspects are also very important. Chromium-free oxidations such as Swern conditions or Dess-Martin periodinane (DMP) are preferred over the classic methods that employ Jones reagent, Collins reagent or PCC/PDC. For the mechanism of the here used Swern protocol, see Chapter 5, p. 86. 

It is not possible to transform an acid in one step selectively into the corresponding aldehyde. Therefore a two-step procedure is normally used The acid is first reduced to the alcohol, which is then oxidized to yield the aldehyde. Under these conditions the pivalyl ester is also reduced to give diol 39 in 99 % yield. Afterwards 39 is oxidized under Swern conditions (Chapter 5, p. 86) and the dialdehyde 29 is obtained in 84 % yield. 

The DIBAL reduction of 11 provides alcohol 28 which is oxidized to the corresponding aldehyde 12 under Swern conditions. Sometimes the intermediate of DIBAL reductions eliminate aluminum alkoxide... 

In this work the (i )-silyalkyne (125) was treated with lithium di-isopropylamide and methyl lithium and then the epoxide (126) was added. This gave the lactone (127) which with potassiiim hydroxide in ethanol produced the protected amino alcohol (128). Reaction of this compound with formalin afforded the cyclopentaoxazolidine (129) and this when heated with one molar equivalent of camphorsulphonic acid and chromatography yielded the indolizidine (130, R=Bn). Deprotection and oxidation under Swern conditions gave the aldehyde (131). Finally a Wittig reaction between this aldehyde and the ylide (132) produced the enone (133) which was reduced with lithium aluminium hydride to yield (+)-pumiliotoxin-B, together with a small amount (-6%) of its erythro-isomer (Scheme 6). 

Commercially available dimethyl cyclopropylmalonate 30 was converted to mono ester 31 by careful saponification using sodium hydroxide. Coupling with l-amino-2-hexanol afforded the hydroxyamide 32 which was oxidized to ketone 33 under Swern conditions. Condensation to oxazole 34 was effectively achieved by utilizing a two-phase system consisting of dichloromethane and sulfuric acid. Reaction with deprotonated dimethyl methylphosphonate gave the 0-ketophosphonate 35 in an excellent overall yield. 

The Swern conditions were applied to a number of substrates with different functional and protecting groups, such as sugar derivatives, protected amino acid derivatives, tartaric acid derivatives, and optically active synthetic intermediates. Both acid-sensitive (epoxide, acetonide, silyl, NBoc, NCBz) and alkaline-sensitive groups (Ac, Bz, ester, silyl) were found to be completely unaffected. The proposed mechanism begins with tautomerisation of the amide to the hydroxy imine, followed by reaction with the dimethylchlorosulfonium species. The resulting oxysulfonium species 63 collapses when treated with base to regenerate DMSO and produce the nitrile. 

With the above consideration in mind, we first prepared the ketone derivative 28 with an acetylenic moiety as a C -unit. The known hydroxyl compound 26, derived from diisopropyl D-tartrate, was consecutively oxidized under Swern conditions and exposed to lithium phenylacetylide to afford an 80% yield of 27, which was again oxidized under Swern conditions to provide 28 in 90% yield (Scheme 6). Stereoselective... 

The first step in the synthesis is an oxidation of the alcohol starting material (via PCC or Swern conditions) to give the needed carbonyl. Reaction of this ketone with the 1,3-dithiane anion shown, followed by hydrolysis, affords the desired TM. 

A facile, preparative-scale synthesis of (21 ,4 )-2-methyl-4-hexenal 1841, a key intermediate in the synthesis of (2S,3J ,4J ,6 )-3-hydroxy-4-methyl-2-methylamino-6-octenoic acid (MeBmt), has been reported [1337]. The hexenal 1841 was prepared by hydrolyzing the starting amide 1838 with sulfuric acid, redudng the resulting acid 1839 with LiAlH4, and oxidizing the resulting alcohol 1840 under the Swern conditions. 

Swern conditions have been applied in the selective oxidation of primary silyl ethers, intermediates in the synthesis of natural products [1322], Thus, primary trimethylsilyl or triethylsilyl ethers 1868, in the presence of secondary trime-thylsilyl or triethylsilyl ethers, are selectively oxidized to the corresponding aldehydes 1869 under Swern conditions. A short synthesis of key intermediates towards various natural products, e.g. leukotrienes, has been achieved. 

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