Trimethylamine ketone synthesis

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

In addition to the Mannich reaction being a valuable method for preparing amino ketones,which are encountered in many drugs, the reaction is also important in organic synthesis in providing a stable equivalent of a conjugated exo-methylene moiety. Thus, addition of methyl iodide to the Mannich base converts it to the quaternary ammonium salt. Subsequent treatment with a base results in a [3-elimination of trimethylamine to generate the a-methylene ketone. 

Carbonyl compounds are an important class among organic molecules. Literature records several methods for their synthesis. However, there are very few methods to convert carbon-carbon unsaturation to carbonyl compounds. Hydroboration of acetylenes, followed by oxidation provides a novel method for carbonyl synthesis. It has been noted that regioselectivities achieved in the monohydroboration of internal acetylenes with thexylborane [1], disiamylbo-rane [1], dicyclohexylborane [1], and catecholborane [2] are similar to, but less pronounced than, that realized by 9-BBN [3]. The B-alkenyl-9-BBN derivatives undergo oxidation to the corresponding ketones or aldehydes under aprotic conditions with trimethylamine N-oxide [4, 5] or under protic conditions by inverse addition to buffered hydrogen peroxide [3]. The inverse addition, i.e., the slow addition of the B-alkenyl-9-BBN in THF to the buffered H O, suppresses the otherwise undesirable protonolysis reaction and favors the oxidation pathway to the desired aldehyde or ketone. 

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