Komblum oxidation

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

Known as the Komblum oxidation, this is peihaps die most widely used and best-known mediod for die oxidation of halides. It works best with activated halides such as benzyl halides, a-halocarbonyl... 

There are some important limitations on the Komblum oxidation, however, as would be expected for a reaction relying on an 5n2 displacement as the first step. Secondary halides are prone to elimination under these conditions. Similarly, if the approach of the DMSO is hindered, e.g. by a 1,3-diaxial interaction, the oxidation proceeds poorly (equation 1). Overoxidation can also occur, at least in steroidal a-bromo ketones (Scheme 3). ... 

Omission of the base in the Komblum oxidation can have interesting consequences. Bromine, produced by the oxidaticm of the liberated HBr by DMSO," may lead to br ination of the primary oxidation product in good yield (equation 2). Note the use of epichlordiydrin as an HBr scavenger (equation 3). 

The Komblum oxidation can be combined with halogenadon to provide a very convenient synthesis of 2 and 4-pyridinecarbaldehydes from the corresponding picolines (equation 4). ... 

A formal total synthesis of ( )-morphine has been achieved by adopting the above synthetic route (Scheme 18). The tetrahydropyridine 91, prepared from the reaction of A/ -methyl-4-piperidone with 2,3-dimethoxy-phenyllithium, followed by dehydration, was converted to the bicyclic en-amine 92 by treatment with the ylic dibromide. Kinetic protonation of 92 with perchloric acid gave the trans-fused immonium salt, which upon dissolution in methanol equilibrated to the thermodynamically prefered cis isomer 93. Treatment of 93 with diazomethane brought about the formation of the aziridinium salt 94, which was readily transformed into the a-amino aldehyde 95 by its oxidation with dimethyl sulfoxide. It is also worth noting that the Komblum oxidation of aziridinium salts leads to the construction of a-amino aldehydes efficiently. Lewis-acid-catalyzed cyclization of 95 afforded the morphinan carbinol 96 in 80% yield. Successive mesylation and reduction of the mesylate derived from 96 with LiBEtjH afforded morphinan (97) in excellent yield. In this instance, direct conversion of 93 to 97 by treatment with diazomethane gave approximately 1 % of the desired product. Lemieux-Johnson oxidation of 97 under acidic conditions furnished the ketone 98, which was previously transformed into ( )-morphine by Gates. In order to confirm the structure of 98, its conversion to the known... 

Komblum oxidation Oxidation of alkyl halides to the corresponding carbonyl compounds using DMSO as the oxidant. 250... 

The availability of 19-iodotabersonine (278) has allowed the partial synthesis of several aspidospermine alkaloids. For example, Komblum oxidation of 278 under anhydrous conditions gives 19-oxotabersonine, which on hydrogenation of the 14,15-double bond affords (-)-minovindne (316)... 

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