Synthetic and Spectroscopic Investigation of N‐Acylated Sulfoximines

Abstract

N-Acylated sulfoximines display unique chemical properties. Various derivatives have been synthesized and investigated by NMR and IR spectroscopy. The results of these studies suggest that the bond between the sulfoximine nitrogen atom and the carbonyl group has a less pronounced double-bond character than the corresponding bond in an amide. This assumption is supported by the first X-ray crystal structure of a sulfoximidoyl derivative. Ab initio calculations (MP2/6-311++G**) provide further insight into the electronic nature of the N-acyl fragment. Studies of the chemical behavior of N-acylated sulfoximines indicate the presence of a highly electrophilic carbonyl group. Thus, the N--C(O) bond can easily be cleaved under mild basic conditions, and the acidity of the hydrogen atoms alpha to the sulfoximine carbonyl group is high. As a consequence of the latter property, endo,endo-sulfoximidoyl norbornene derivatives readily isomerize to their endo,exo counterparts, and sulfoximine-containing pseudopeptides can easily epimerize at the stereogenic center next to the N--C(O) carbonyl group.

A General Copper‐Promoted Coupling of Sulfoximines with Vinyl Bromides

“…For example, Porco and co-workers synthesized several antitumor macrolides [4] and antibiotics [5] by coppermediated vinylic substitution, and Kozawa and Mori prepared a carbapenem derivative by intramolecular palladium-catalyzed coupling of a b-lactam with a vinyl bromide. [6] On the other hand, we have been interested in the introduction of various carbon substituents (such as acyl, [7] alkyl [8] or aryl [9] groups) on the nitrogen atom of sulfoximines. [10] The resulting compounds can then, for instance, be used as benzothiazine building blocks [11] or incorporated (as pseudo-b-amino acids) in peptidic chains.…”

Asymmetric Synthesis of Chiral Sulfoximines through the S‐Alkylation of Sulfinamides

“…[12] Racemic 11 is an intermediate in the total synthesis of BAY1143572 by Bayer, [3c] and our study contributes to the formal synthesis of BAY1143572 via an enantiomerically pure intermediate. Theobtained sulfinamide,which was used directly for the second alkylation without purification, was converted into the sulfoximine (R)-10 by an S-alkylation with 3-nitrobenzyl bromide in good yield.…”

“…[10] We began our investigation by developing as ulfur-selective alkylation of as ulfinamide with an alkyl iodide under basic conditions.T oprevent the preferential N-alkylation, the steric and electronic properties of the nitrogen atom of acommercially available (rac)-tert-butanesulfinamide [11] were modified by introducing av ariety of substituents.H owever, most reactions of sulfinamides with ethyl iodide in the presence of NaH gave only at race amount of the desired sulfoximine along with N-alkylation products (Scheme 1a). [12] We then optimized the reaction conditions to improve the yield and the S-selectivity as shown in Table 1( details are provided in the Supporting Information). [12] We then optimized the reaction conditions to improve the yield and the S-selectivity as shown in Table 1( details are provided in the Supporting Information).…”

Gold(I)‐Catalyzed 6‐endo‐Dig Hydrative Cyclization of an Alkyne‐Tethered Ynamide: Access to 1,6‐Dihydropyridin‐2(3H)ones

“…[18] Unfortunately, the reaction of 2 a under the optimized conditions (Table 1, entry 5) did not afford the cyclized product 3 a even in trace amounts, ruling out the possible involvement of 2 a as an intermediate in the synthesis of 3 a (Scheme 5). To validate this presumption, substrate 2 a was prepared from 1''a and phenylacetic acid through N'-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) coupling.…”