Swern oxidation conditions

Unsubstituted hydrazones of aromatic ketones and aldehydes have been converted in high yield to alkyl chlorides under Swern oxidation conditions, although the substrate actually undergoes a net reduction.93 When the hydrazone is dideuterated, a deuterium ends up on the carbon, supporting the proposed intermediacy of cation (34), which tautomerizes and loses N2, to give a carbocation which combines with the chloride. 

Odourless and non-volatile organosulfur compounds grafted to an imidazolium ionic liquid scaffold has been synthesized. The sulfoxides have been used for an efficient oxidation of primary allylic and benzylic alcohols into aldehydes and secondary alcohols to ketones under Swern oxidation conditions and the corresponding sulfides can be recovered and recycled.110... 

The unsubstituted hydrazones derived from aromatic ketones and aldehydes are converted to the corresponding alkyl chlorides, in high yield, under Swern oxidation conditions. In this unusual oxidation/reduction sequence, the substrate undergoes a net reduction. Unsubstituted hydrazones derived from cyclohexyl ketones yielded elimination products. The mechanism in Scheme 7 has been postulated.111... 

The synthesis of the 1,6-linked ester was straightforward as outlined in Scheme 6. We were able to convert alcohol 23 to aldehyde 24 using Swern oxidation conditions. Wittig reaction was followed by olefin reduction and saponification to bring the sequence as far as 26. Esterification of 26 with olefin alcohol la, mediated by DCC, then afforded the target ester 27 in good overall yield (13). 

The first total synthesis of the marine dolabellane diterpene (+)-deoxyneodolabelline was achieved in the laboratory of D.R. WilliamsJ In the final step of the synthetic sequence, the oxidation of a secondary alcohol functionality of a 1,2-diol to the corresponding a-hydroxy ketone was required. Such 1,2-diols are known to be unstable under most oxidation conditions, and often glycol cleavage is observed. Indeed, when Dess-Martin and Ley oxidations were tried, the substrate suffered carbon-carbon bond cleavage. However, under the Swern oxidation conditions, the desired a-hydroxy ketone was isolated in a 65% yield. Interestingly, the substrate was a mixture of four inseparable diastereomeric diols (obtained in a McMurry reaction), which gave two easily separable ketone products, one of which was the natural product. 

S.F. Martin and co-workers utilized a double Swern oxidation in their synthesis of ircinal A and related manzamine alkaloids. The advanced tricyclic did intermediate was first subjected to the Swern oxidation conditions at -78 °C to afford the corresponding dialdehyde in excellent yield. In the next step, the dialdehyde was exposed to excess Wittig reagent under salt-free conditions to form the two terminal alkenes. 

Swern oxidation of N-unsubstituted aziridine-2-phosphonates resulted in the formation of both 2H-azirine-2-phosphonates and 2H-azirine-3-phosphonates [81, 83]. Treatment of ds-aziridine-2-phosphonate 226 (Scheme 3.84) with DM SO/ (COCl)2/Et3N afforded azirine-phosphonates 227 and 228, with the former predominating [81]. Under similar conditions, however, trans-aziridine-2-phospho-... 

The second synthesis of crystalline 43 was reported by Mori as summarized in Scheme 62 [93]. The building block (4.R,5S)-A was prepared by an enzymatic process, while another building block C was synthesized via Sharpless asymmetric epoxidation. Coupling of A with C gave D, which was cyclized under Op-polzer s conditions to give crystalline E. When E was oxidized with Dess-Martin periodinane or tetra(n-propyl)ammonium perruthenate or Jones chromic acid, crystalline 43 was obtained. Swern oxidation or oxidation with 2,2,6,6-tetramethylpiperidin-1 -oxyl of E afforded only oily materials. Accordingly, oxidation of E to 43 must be executed extremely carefully. A synthesis of oily 43 was reported by Gil [94]. 

The Swern oxidation is a preparatively important reaction which allows for the oxidation of primary and secondary alcohols 1 to aldehydes and ketones 2, respectively, under mild conditions, using activated dimethyl sulfoxide (DMSO) as the oxidizing agent. 

The Homer-Emmons addition of dialkyl carboalkoxymethylenephosphonates to aldehydes [22] has been widely used to generate a,p-unsaturated esters which, in turn, can be reduced to allylic alcohols. Under the original conditions of the Homer-Emmons reaction, the stereochemistry of the oc,(3-unsaturated ester is predominantly trans and therefore the trans allylic alcohol is obtained upon reduction. Still and Gennari have introduced an important modification of the Homer-Emmons reaction, which shifts the stereochemistry of the a,[i-unsaturated ester to predominantly cis [23], Diisobutylaluminum hydride (DIBAL) has frequently been used for reduction of the alkoxycarbonyl to the primary alcohol functionality. The aldehyde needed for reaction with the Homer-Emmons reagent may be derived via Swern oxidation [24] of a primary alcohol. The net result is that one frequently sees the reaction sequence shown in Eq. 6A. 1 used for the net preparation of 3E and 3Z allylic alcohols. 

These reactions only operate on very sensitive substrates, and protecting groups removable under basic conditions normally resist a Swern oxidation. 

The use of moist DMSO causes the generation of adventitious HC1, that produces the transformation of the allylic alcohol into an allylic chloride. A properly performed Swern oxidation, under anhydrous conditions, allows the obtention of the desired dialdehyde in... 

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. 

A 62.5% yield of the desired ketone with no epimerization at the ot-position is obtained, employing catalytic TPAP as oxidant. Other oxidizing conditions, including Collins, Sarett, Oppenauer and Swern oxidations, as well as PCC, fail to deliver an acceptable yield of... 

After trying many oxidizing conditions, it was found that the Mukaiyama procedure is the most suitable. The oxidation also succeeds employing a Swern oxidation, although the corresponding work-up is more difficult. 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

Fig. 5. A Swern oxidation under fluorous conditions allows reuse of the suph-oxide reagent.

In our procedure methyl ester 3 is obtained by the McKillop method.2 Conditions and yields of steps A and B are essentially identical to those reported by McKillop. The reduction of crude 3 with lithium aluminum hydride (step C) to the alcohol 4 was essentially quantitative. Also this isolated compound did not require any purification for use in the next oxidation step (D). This was carried out by the Swern oxidation method12 using DMSO and (COCI)2 in the presence of a base. This crucial operation where Roush obtained considerable racemization of the resulting amino aldehyde 5, was carried out in the presence of diisopropylethylamine13 (Hunig s base). This simple yet important modification provided 5 in good yield (79-85% from 1) and enantiomeric purity (96-98%) comparable to that reported by Garner. 

Scheme 5.46. Synthesis of key epothilone fragments using DERA. Conditions (a) 42% yield (b) Br2/H20 (c) 35% (d) (i) Ac20, pyridine, (ii) BF3/Et20 (e) HS(CH2)3SH/BF3/Et20 (/) (i) Swern oxidation, (ii) Wittig reaction (g) (i) Swern oxidation, (ii) Wittig reaction TBS = tert-butyldimethylsilyl TIPS = triisopropylsilyl.

TMS ethers of primary alcohols and most secondary alcohols do not survive even the simplest synthetic manipulations — especially if protic solvents are involved. For example, Swern oxidation or Collins oxidation conditions will cleave a primary TMS ether and perform the oxidation in the presence of a secondary TMS ether.3 Owing to the sensitivity of TMS ethers., deprotection can usually be achieved under very mild conditions (e,g., acetic acid or potassium carbonate in methanol). The rate of hydrolysis depends on both steric and electronic effects with hindered environments decreasing the rate and electron-withdrawing substituents on the hydroxyl function increasing the rate. In a synthesis of Zaragozic Acid A. the... 

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