Homologation, asymmetric synthesis

SCHEME 72. Iterative one-pot homologation of reduced polypropionates viaZACA-Pd-catalyzed vinylation and its application to highly efficient catalytic and asymmetric synthesis of key intermediates of ionomycin and borrelidin... 

Despite the number of reports of the asymmetric synthesis of tertiary a-aryl cyclohexanones, there have only been three reports which describe the asymmetric synthesis of tertiary a-aryl cyclopentanones. The first of these was reported by Shi via asymmetric epoxidation of benzylidene cyclobutanes and epoxide rearrangement in a subsequent step [76]. Backvall used a dynamic kinetic resolution of aUyhc alcohols-aUylic substitution-oxidative cleavage sequence to access 2-phenylcyclopentanone [77]. The first direct catalytic asymmetric synthesis of tertiary a-aryl ketones was recently described by Kingsbury using a series of Sc-catalysed diazoalkane-carbonyl homologations with bis/tris oxazohne ligands [78]. 

In 2009, Wang et al. developed an asymmetric synthesis of 3-hydroxyl-2-alkanones via a tandem organocatalytic aminoxylation of aldehydes and a chemoselective diazomethane homologation. An accelerating effect of water was observed for the aminoxylation catalysed by L-proline, while MgCl2 served... 

The essential features of the Masamune-Sharpless hexose synthesis strategy are outlined in a general way in Scheme 4. The strategy is based on the reiterative- application of a two-carbon extension cycle. One cycle comprises the following four key transformations (I) homologation of an aldehyde to an allylic alcohol (II) Sharpless asymmetric epoxidation of the allylic alcohol ... 

As chiral cyanohydrins are important synthetic intermediates for the preparation of chiral amino acids, carbohydrates, and so on, this process would be a useful asymmetric one—carbon homologation procedure widely employable for organic synthesis. 

An important transformation of dialdoses is the chain extension to homologous products by condensations performed on the aldehyde group. When asymmetric induction occurs, this transformation is extremely valuable for the stereocontrolled synthesis of higher sugars. 

After TMSOTf-mediated deprotection, the further transformations used to furnish (+)-CP-263,114 (ent-1) and (—)-CP-225,917 (ent-2) employ common homologation steps, for the most part already used in Nicolaou s asymmetric total synthesis. 

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