Regio‐ and Stereoselective Synthesis of Fully Substituted Silyl Enol Ethers of Ketones and Aldehydes in Acyclic Systems

Abstract

The regio-and stereoselective preparation of fully substituted and stereodefined silyl enol ethers of ketones and aldehydes through an allyl-Brook rearrangement is reported. This fast and efficient method proceeds from am ixture of Eand Zisomers of easily accessible starting materials.

Stereoselective Access to Fully Substituted Aldehyde‐Derived Silyl Enol Ethers by Iridium‐Catalyzed Alkene Isomerization

“…While these efforts have firmly established access to stereodefined enolates of amides, esters, and ketones, fully substituted enolates of aldehydes have proven significantly more challenging. Reported strategies (Scheme a–c) mandate the manipulation of sensitive organometallic species at cryogenic temperatures or the use of stoichiometric amounts of transition metal mediators, leaving additional room for improvement in this challenging field.…”

“…Our previous efforts in the area of fully substituted enolates, combined with a growing interest in the strategic use of alkene isomerization in organic synthesis, led us to devise a new line of attack towards the above goal, powered by alkene isomerization. Specifically, we envisioned the thermodynamically driven isomerization of 2,3‐disubstituted primary allylic silyl ethers en route to fully substituted aldehyde‐derived silyl enol ethers (Scheme d).…”

Construction of Acyclic Vicinal Tertiary and Quaternary Carbon Stereocenters via a Pd‐Catalyzed Allylic Alkylation of Stereodefined Polysubstituted Ketene Aminals

“…Although the transformation proceeds with high enantio‐ and diastereoselectivity for 2‐phenylpropionaldehyde as reported in Scheme c, the diastereoselectivity for non‐aromatic branched aldehydes decreases due to the difficulty to control the stereochemistry of the fully‐substituted enamine intermediate . In the last few years, we and others have been interested in developing straightforward access to stereodefined acyclic fully substituted enolate, silyl enol ether and silyl ketene aminal derivatives . In the last case, our approach resulted from the stereo‐ and regioselective carbometalation of ynamides followed by an oxidation of the resulting organocuprates with an in‐situ generated oxenoid (Scheme d).…”

“…Then, addition of aldehydes (or imines) lead to the aldol (or Mannich) products whereas the addition of trialkylsilyl chloride or allyl chloroformate (AllocCl) gave an easy access to the formation of acyclic stereodefined disubstituted silyl ketene aminals 1 and allyloxycarbonyl amide enolate as unique isomer (Scheme d),[8a], , en route to the formation of acyclic quaternary stereocenters e) starting from easily accessible disubstituted silyl ketene aminals 1 (single‐pot operation from ynamide).…”

C(sp2)−Si Bond Functionalization through Intramolecular Activation by Alkoxides

“…Hence, the stereoselective formation of alkenylcopper intermediates is obtained, and their functionalization, with retention of the double‐bond geometry, can be performed through electrophilic substitution. This method provides direct access to tetrasubstituted silyl enol ethers 46 , which are particularly useful reagents for the construction of quaternary stereogenic centers [39] …”