Rapid and Stereochemically Flexible Synthesis of Polypropionates: Super‐Silyl‐Governed Aldol Cascades

Supersilyl Protective Groups in Aldol Reactions

“…Alanine-derived (S)-N-benzyl-N-tosyl-2-amino-propanal showed excellent selectivity, giving the syn-syn Felkin product 11. Importantly, control experiments revealed no substantial racemization of the chiral α-substituted aldehydes under reaction conditions [33,59].…”

“…Interestingly, changing the catalyst to (0.05 mol%) TMS 3 Si · NTf 2 , (generated by metathesis of AgNTf 2 and (TMS) 3 SiCl) [30,31] gave nearly identical results in terms of both yield and selectivity (entries 6 and 8), validating the hypothesis that this is the active catalyst. Later, the E-SEE of propionaldehyde E−2 was synthesized [32] in diastereomerically pure form and R 1 OSi R 1 CHO X X OSi R 1 CHO X 1: X = H, Si = (TMS) 3 Si Z-2: X = CH 3 , Si = (TMS) 3 Si a E-2: X = CH 3 , Si = (TMS) 3 Si b E-3: X = CH 3 , Si = (TES) 3 was also found to be effective in aldol reactions with simple aldehydes [33]. Interestingly, E-2 gave anti-products, complementing the syn-selectivity of Z−2 ( [93,94,98,99] in natural products have led to a great interest in the development of methods for stereoselective halogenation.…”

“…The aldol reaction has been widely employed for the synthesis of natural products bearing the polypropionate motif [68]. Sequential aldol-aldol reactions with propionaldehyde-derived SEEs E-2 and Z-2 would provide a rapid approach to construction of these challenging yet important structures [33]. A mixed-triple aldol cascade involving initial reaction of cyclohexane carboxaldehyde and one unit Z-2 followed by addition of two units of 1 generated 28, bearing 3,5,6,7-syn-syn-syn stereochemistry in 57% yield (Eq.…”

Stereoselective one-pot synthesis of polypropionates

“…In addition, the stereochemical control of the newly created stereocentres over the course of the propionate chain elongation is often complicated. Attractive alternatives, especially considering atom and step economy, are multicomponent domino (or cascade) reactions 17–19 that could create more than one C–C bond, and hence, multiple stereocentres in a single-pot operation. Nevertheless, only particular sets of stereoisomers could be achieved in these procedures.…”

The Supersilyl Group as a Carboxylic Acid Protecting Group: Application to Highly Stereoselective Aldol and Mannich Reactions

“…[1,2] As part of our continuing studies on tris (trialkylsilyl)silyl (“supersilyl”) group, we have developed the “supersilyl” directed aldol reactions of β-siloxy methyl ketones and cascade Mukaiyama aldol reactions, which enabled the rapid assembly of polyol motifs and expedient synthesis of polyketide natural products. [3] The “supersilyl” group, with unique electronic properties and large steric bulk, has been discovered to play a crucial role in obtaining high yields and selectivities. [3] Encouraged especially by the stability and steric encumbrance of “supersilyl” ether motifs, we reasoned that the "supersilyl" group might be able to offer the necessary robustness for silyl esters as it is well-known that the stability of silyl esters, like that of silyl ethers, parallels the steric bulk of the silyl group.…”