Controlling stereochemistry in polyketide synthesis: 1,3- vs. 1,2-asymmetric induction in methyl ketone aldol additions to β-super siloxy aldehydes

Abstract

The aldol addition of methyl ketones to b-siloxy and a-methyl b-siloxy aldehydes is described. Careful control of mechanistically distinct aldol reactions leverages 1,2-and 1,3-asymmetric induction, selectively forming syn and anti aldol adducts with excellent diastereocontrol. Experimental and theoretical investigations have provided insight to the factors governing diastereoselectivity.

A highly diastereoselective “super silyl” governed aldol reaction: synthesis of α,β-dioxyaldehydes and 1,2,3-triols

“…Recently our group has actively investigated the Mukaiyama aldol reaction of tris(trimethylsilyl)silyl “super silyl” enol ethers for the highly diastereoselective synthesis of β-super siloxy aldehydes and α-halo-β-super siloxy aldehydes employing Lewis acid catalysis. 3 This efficient methodology allows for a rapid and stereoselective construction of mono-, bis- and tris-hydroxyaldehydes through mono, double and triple cross aldol processes, respectively, affording polyketide-like scaffolds which are particularly useful for the oriented construction of complex natural polyketides. In our continuous studies on Mukaiyama aldol reactions of super silyl enol ethers, we questioned whether a similar strategy might provide access to α,β-dioxygenated aldehydes which could be a useful building block for construction of complex sugar moieties.…”

Phosphine Oxide-Catalyzed Asymmetric Aldol Reactions and Double Aldol Reactions

“…1-a). Yamamoto and colleagues reported that the tris(trimethylsilyl) silyl (super-silyl) enol ether undergoes a triple aldol reaction [62][63][64][65] (Fig. 1-b) in a highly syn-selective manner, due to the strong steric effect of the super-silyl group.…”

Oxazaborolidinone-Mediated Asymmetric Bisvinylogous Mukaiyama Aldol Reaction

“…In contrast, the use of larger B­(C 6 F 5 ) 3 ·H 2 O favored the formation of the 1,3- syn product 5s (see Supporting Information). This observation is in accordance with previous findings by Yamamoto and co-workers . For the corresponding PMB protected substrate, no clear tendency could be observed, with yields and selectivities contradicting each other (Table , entries 5 and 6).…”

“…This observation is in accordance with previous findings by Yamamoto and co-workers. 14 For the corresponding PMB protected substrate, no clear tendency could be observed, with yields and selectivities contradicting each other (Table 3, entries 5 and 6). With acetonide protected dihydroxy aldehyde 4q both syn-and anti-product could be obtained with excellent selectivities, depending on the enantiomer of Lewis acid used.…”