ChemInform Abstract: Aldol Reactions of Nortropinone Derivatives in Solution and on Solid Phase.

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

“…The hydrazones of the immobilized ketones and aldehydes could be lithiated with LDA and alkylated with alkyl halides. 62,303,304,309 The alkylated products were isolated in good yields (47-94%) and typically in acceptable purity (59-91%). 62 This alkylation method al-lowed for the expansion of the carbon skeleton of carbonyl compounds.…”

“…The protected, polymeric hydrazines needed activation by washing with 10% TFA solution in wet THF prior to loading of a new ketone or aldehyde. The hydrazones of the immobilized ketones and aldehydes could be lithiated with LDA and alkylated with alkyl halides. ,,, The alkylated products were isolated in good yields (47−94%) and typically in acceptable purity (59−91%) . This alkylation method allowed for the expansion of the carbon skeleton of carbonyl compounds.…”

Solid-phase Synthesis of Tertiary N-Methyl Amines Including Tropanes

“…To allow for application of highly reactive and basic conditions of enolate chemistry, which have been successfully used for synthesis of various tropane derivatives in solution, [48][49][50] to reactions of immobilized nortropinone the linker should be sufficiently robust. Although our initial studies 14,51 showed that triazene T2, 14,18 and Wang carbamate 46 anchored nortropinone could be used in supported synthesis based on enolate chemistry the cleaved nortropanes needed additional post cleavage N-methylation. Thus we turned our attention to the Wang resin that has been used for binding amines and releasing them after modification as sulfonamides 37 or even primary amines.…”

“…Unfortunately, our attempts to release unchanged secondary amines especially nortropane derivatives were only partially successful and complicated by byproduct of linker cleavage (Scheme ). Cleavage of nortropinone and even a simple test amine, morpholine, from the Wang polymer with TFA resulted in a mixture of cleaved amine e.g., 1 and its N -( para -hydroxybenzyl) derivative 11 in ∼1:1 ratio (Scheme , Table , resin 6 ) …”

“…Cleavage of nortropinone and even a simple test amine, morpholine, from the Wang polymer with TFA resulted in a mixture of cleaved amine e.g., 1 and its N-(para-hydroxybenzyl) derivative 11 in ∼1:1 ratio (Scheme 2, Table 1, resin 6). 51 To directly obtain the N-methylated tropane derivatives we investigated a possibility of of supported nortropane followed by cleavage by debenzylation. W reasoned that some known from solution synthesis debenzylations of quaternary ammonium salts such as thermal decomposition, [52][53][54][55] or better, nucleophilic displacement with amines (e.g., with morpholine), 36 thiophenol, 56,57 triphenylphosphine 58 or sodium acetate in glacial acetic acid, 59 could perhaps be combined with N-methylation to get access to N-methylated tertiary amines including tropinone or other tropane derivatives.…”