Swern oxidation, and

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

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. 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

Fluorous-tagged reagents are very attractive for reactions in which a stoichiometric by-product is formed that is difficult to separate. An example is perfluor-oalkylated triphenylphosphane for use in Wittig and aza-Wittig reactions, where the corresponding phosphane oxide is removed by fluorous extraction [22, 23]. Similarly, fluorous sulfoxide has been employed in Swern oxidations, and fluorous carbodiimide has been used as a coupling reagent [24, 25]. 

Heathcock has used a remarkable cascade of reactions, including an intramolecular Diels-Alder reaction of a protonated 2-aza-diene, in the synthesis of Daphniphyllum alkaloids. We give one example. The diol 92 gives the unstable dialdehyde 93 by Swern oxidation and hence the protonated... 

Methyl a-D-glncopyranoside (16) has been used as a precursor for the synthesis of (-1-)-castanospermine (1) (Scheme 2). The aldehyde 17, prepared from 16, was allylated " to give a 9 1 ratio of epimers, which upon chromatographic separation andbenzylation of the major prodnct afforded 18, which underwent ring opening to give 19. Swern oxidation and... 

Hence, monoprotection of 1,4-butanediol with Nall and trapping with allyl bromide led to 4-allyloxybutan-l-ol (Scheme 21). The crude product was treated with Jones reagent to furnish 4-allyloxybutyric acid (73). Treatment with oxalyl chloride in hexane at room temperature gave the corresponding acid chloride, which reacted with A-oxazoiidinone enolate to give a substrate for asymmetric alkylation upon treatment with NaHMDS and Mel. Reduction of 74 with lithium aluminum hydride led to a primary alcohol and recovered chiral auxiliary. Swern oxidation and treatment with Ph3PCHCOOMe afforded the a,P-unsaturatcd ester 75. 

Di-0-benzyl-3,4-0-isopropylidene-D-mannitol was ring closed to afford a 9 1 cis/trans mixture of 189 in high yield by (Swern) oxidation and radical cyclization of the dialdehyde using samarium iodide in fcrf-butanol. The cis-diastereoisomer was selectively converted into a cis-cyclic sulfate which underwent cleavage upon treatment with potassium tert-butoxide to afford a cyclo-... 

This reaction is related to the Dess-Martin Oxidation, Swern Oxidation, and Pfitzner-Moffatt Oxidation. 

After protection of the alcohol function, the carbonyl group is converted into a methylene group by means of the Tebbe reagent, followed by a Swern oxidation and a Homer-Wadsworth-Emmons reaction. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

Greenes synthesis starts from (S)-phenylglycine. [331 ] The corresponding amino-alcohol is reacted with benzoyl chloride. After Swern oxidation and a Grig-nard reaction, an aUyl alcohol is obtained. After protection of the alcohol function, the desired product results from periodate cleavage. 

Now let us consider some specific oxidation methods that hinge on the general mechanism shown above the Swern oxidation, and oxidations involving chromate esters. 

Oxidations involving chromium (VI) reagents such as H2Cr04 are simple to carry out and have been widely used. These reactions involve formation of chromate esters, and include an elimination step similar to the general mechanisms shown in Section 12.4A. Chromium (VI) is a carcinogen and an environmental hazard, however. For this reason, methods like the Swern oxidation and others are increasingly important. 

Ketones from secondary alcohols by Swern oxidation and other methods (discussed in Section 12.4) ... 

In Zhu s approach, the advanced intermediate 34 was subjected to Swern oxidation and tetra- -butyIammonium fluoride (TBAF)-mediated deprotection of the silyl ether, yielding a mixture of aldehyde 35 and hemiaminal 36. Treatment of this mixture with 0.01% v/v methanesulfonic acid in dichloromethane initiated a process consisting of acyhminium formation, deprotonation, and domino P-elimination/cydization. Thus, dehydration of hemiaminal 36 initially led to iminium ion 37, which formed enamide 38 under loss of a proton. Elimination of the sulfur side chain then resulted in conjugated iminium ion 39, which was set up to undergo a phenolic Mannich cych2ation. 

Ene-yne metathesis has been employed in an elegant synthesis of stemoamide 8.415 (Scheme 8.112). The starting lactam 8.407, available itself from glutamic acid, was iV-alkylated, then subjected to deprotection, Swern oxidation and application of the Corey-Fuchs method for installation of an alkyne by Wittig... 

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