Asymmetric Catalytic [2,3] Stevens and Sommelet–Hauser Rearrangements of α‐Diazo Pyrazoleamides with Sulfides

Abstract

Catalytic enantioselective [2,3] Stevens and Sommelet-Hauser rearrangements of a-diazo pyrazoleamides with sulfides were achieved by utilizing chiral N,N'-dioxide/nickel-( II )c omplex catalysts.T hese rearrangements proceeded well under mild reaction conditions,p roviding rapid and facile access to aseries of functionalized1,6-dicarbonyls or sulfanesubstituted phenylacetates with high to excellent enantioselectivities.T he catalytic system shows excellent stereocontrol, discriminating between the heterotopic lone pairs of sulfur and controlling both the 1,3-proton transfer and the [2,3]-s rearrangement.Scheme 1. Sulfur-containing drugs and catalytic asymmetric [2,3] sigmatropic rearrangements.

Asymmetric Catalytic [2,3] Stevens and Sommelet–Hauser Rearrangements of α‐Diazo Pyrazoleamides with Sulfides

“…According to our previous work, [10a] the absolute configuration of the major products, [12,16] control experiments,a nd deuterium-labelling experiments,a sw ell as the general mechanism of [2,3] sigmatropic rearrangements, [18] the catalytic models for the enantiocontrol in the [2,3] Stevens and Sommelet-Hauser rearrangements are proposed ( Figure 1). When 1a is mixed with the chiral nickel(II) complex catalyst (Figure 1b,t op), decomposition by loss of nitrogen proceeds readily to form chiral nickel carbene intermediate A1.T he (phenylthio)acetate prefers to attack from the Re-face of nickel carbene because the Si-face is blocked by the left amide unit of the ligand (Figure 1a).…”

“…Thed iazo compounds bearing a2naphthyl group and heterocyclic rings,also performed well to yield the corresponding products (3g-j)inexcellent enantioand diastereoselectivities (entries 7-10). Subsequently,t he scope with respect to the phenylthioacetate derivatives 2 was also examined ( Table 2, entries [11][12][13][14][15][16][17]. Furthermore,i faZ/E mixture of 1a was used for the reaction, it was found that am ajority of (Z)-1a was recovered, and the E isomer was consumed, yielding 3a in 46 %yield, 84:16 d.r.…”

“…Thelow yields of the furyl-containing products 3h and 3i were attributed to the quick decomposition of the corresponding diazo substrates (entries 8a nd 9). The meta-a nd para-substituents on the phenyl group of the sulfides 2 had little influence on the reactivity,and all the reactions were complete within 15-30 minutes.A ss hown in Table 2, arylthioacetates (2)s ubstituted with electron-donating and electron-withdrawing groups were transformed into the corresponding products (4a-f)in69-84 %yield with 78:22 to 83:17 d.r.a nd 93:7 to 96:4 er (entries [11][12][13][14][15][16]. and 97:3 er.…”

“…Furthermore,i faZ/E mixture of 1a was used for the reaction, it was found that am ajority of (Z)-1a was recovered, and the E isomer was consumed, yielding 3a in 46 %yield, 84:16 d.r. [12] Encouraged by the outcomes in the asymmetric [2,3] Stevens rearrangement, we turned our attention to the enantioselective Sommelet-Hauser rearrangement of arylsubstituted a-diazo pyrazoleamides (5)w ith sulfides.I nitially,t he adiazo(phenyl) pyrazoleamide 5a and sulfide 2a were employed as the model substrates to optimize the reaction conditions (Table 3). It indicated that the (Z)-1a was unfavorable in this asymmetric [2,3] Stevens rearrangement.…”

“…After careful screening of the solvents,C H 3 CN proved to be best choice, and 6a was isolated in 57 %yield with 80.5:19.5 e.r. [16] To determine the mechanism of these two types of [2,3] sigmatropic rearrangement reactions,aseries of experiments were conducted. No better results were observed when different ester groups of the sulfides 2 were examined (see Table S9).…”