Diastereoselective Aza‐Mislow–Evans Rearrangement of N‐Acyl tert‐Butanesulfinamides into α‐Sulfenyloxy Carboxamides

Abstract

Ad iastereoselective [2,3] rearrangement of O-silyl N-sulfinyl N,O-ketene acetals derived from chiral N-acyl tertbutanesulfinamides was developed, giving a-sulfenyloxy carboxamides with excellent enantioselectivity.E nolization and subsequent silylation of N-acyl tert-butanesulfinamides initiate this aza variant of the Mislow-Evans rearrangement, in which the chirality at the sulfur atom in the rearrangement precursors is faithfully transferred to the a-carbon stereocenter of the products.T he Ellman sulfinamide,o ften used as ac hiral ammonia equivalent, can serve in this rearrangement as ac hiral precursor for the asymmetric synthesis of a-oxygenfunctionalizedc arboxamides. Scheme 1. [2,3] Rearrangement of N-acyl tert-butanesulfinamides via O-silyl N-sulfinyl N,O-ketene acetal intermediates and related processes. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 3. Cleavage of the SÀOb ond of a-sulfenyloxy amides and oxidation of the tert-butanesulfenate ester. m-CPBA = m-chloroperbenzoic acid.Scheme 4. Rationalization of the observed stereochemical outcome. Angewandte Chemie Communications 15585

Modern Synthesis and Chemistry of Stabilized Ketene N,O-Acetals

“…Lastly, in 2018, Lu and co-workers proposed an aza variant of the Mislow-Evans rearrangement (Table 17). 98 This transformation capitalized on in situ formation of Nsulfinyl ketene N,O-acetals from N-acyl sulfinamides 88aza and provided access to versatile, carboxamide building blocks 89a-za with excellent diastereoselectivity. Furthermore, the importance of the ketene moiety was confirmed in a control experiment as, in the absence of silylation, no product formation was observed.…”

Trapping the Transition State in a [2,3]-Sigmatropic Rearrangement by Applying Pressure

“…The rearrangement of allylic sulfoxides to allylic sulfenate esters is a popular example of [2,3]sigmatropic rearrangements. [1][2][3] This type of reaction is also known as Mislow-Evans rearrangement [4][5][6][7][8][9][10][11] and is widely used in asymmetric synthesis due to the possibility of chirality transfer from the carbon bearing the sulfoxide group to the alcohol resulting from a subsequent reaction with an appropriate thiophile (Figure 1A).…”

“…The rearrangement of allylic sulfoxides to allylic sulfenate esters is a popular example of [2,3]sigmatropic rearrangements. [1][2][3] This type of reaction is also known as Mislow-Evans rearrangement [4][5][6][7][8][9][10][11] and is widely used in asymmetric synthesis due to the possibility of chirality transfer from the carbon bearing the sulfoxide group to the alcohol resulting from a subsequent reaction with an appropriate thiophile (Figure 1A). Hence, the Mislow-Evans rearrangement is a popular tool in the synthesis of bioactive substances and natural products like terpenes, [12] vernolepin, [13,14] amphidinol 3, [15] and pyrenolide D. [16] The transition state of the Mislow-Evans rearrangement has attracted considerable attention, because it determines the stereochemistry of the reaction.…”

Addition–Rearrangement of Ketenes with Lithium N-tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives

“…Our previous studies demonstrated highly stereoselective [2,3]-sigmatropic rearrangement of O-silyl N-tert-butanesulfin- In this rearrangement, chiral information was transferred from the sulfur atom in the sulfinyl group to the α-position in the amide products. 16 Consequently, Ellman's tert-butanesulfinamide, 17 commonly used as a chiral ammonia equivalent, works well as a latent chiral hydroxyl group. We envisaged that aza-Mislow−Evans rearrangement 18 could lead to O,N-bifunctionalization of disubstituted ketenes: addition of lithiated N-substituted tert-butanesulfinamides to disubstituted ketenes, followed by silylation, might give fully substituted O-silylated enolates, which in turn might undergo rearrangement to give tertiary α-sulfenyloxy carboxamides (Scheme 1c).…”