Aldol/reduction amination strategy

Scheme 7.8 Application of aldol/reduction amination strategy formal synthesis of lopin...

Following the aforementioned chemoenzymatic strategy the aldol adducts from the enzymatic addition were first dephosphorylated and then treated with H2 in the presence of Pd/C. Under these conditions the Cbz group removal and the reductive amination took place in one pot, the iminosugars being obtained as hydrochlorides upon lyophilization at pH 6.5. Figure 19.6 depicts the structure of the iminosugars obtained, either as diasteromeric mixtures or pure compounds, from the N-Cbz-amino aldehydes described in this account. 

Menche recently established an effective two step strategy for synthesizing chiral 1,3 amino alcohols [26]. The first step, an enantioselective aldol reaction, provides chiral (3 hydroxy ketones, which are then reductively aminated under the conditions ofp anisidine (2.0 equiv), Ti(Oi Pr), (1.4 equiv), CH3CN ( 20 °C), in the presence of polymethylhydrosilane (2.2 equiv) over 48 h. A variety of examples are shown in Figure 7.4. 

As detailed in Sections 42.2 and 42.3, both covalent and non-covalent organocatalytic activation modes have provided efficient strategies to design asymmetric MCRs. A quite recent study by Zhou and list has demonstrated the feasibility of combining asymmetric Bronsted acid catalysis with aminocatalysis to design even more sophisticated reaction sequences toward the synthesis of useful complex molecules. Specifically, they developed a highly enantioselective approach to pharmaceutically relevant 3-substituted cyclohexylamines from 2,6-diketones 223 via an aldolization/dehydration/conjugate reduction/reductive amination domino... 

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