Cross‐Coupling Reaction of Alkenyl Sulfoximines and Alkenyl Aminosulfoxonium Salts with Organozincs by Dual Nickel Catalysis and Lewis Acid Promotion

Abstract

In this article, the cross-coupling reaction( CCR) of exocyclic, axially chiral, and acyclic alkenyl (N-methyl)sulfoximines with alkyl-and arylzincs is described . The CCR generally requires dual Ni catalysis and MgBr 2 promotion, which is effective in diethyl ether but not in THF.N MR spectroscopy revealedacomplexation of alkenyl sulfoximines by MgBr 2 in diethyle ther,w hichs uggestsa na cceleration of the oxidative addition through nucleofugal activation.T he CCR of alkenyl sulfoximinesg enerally proceedsi nt he presence of Ni(dppp)Cl 2 as ap recatalyst and MgBr 2 with alkyl-and arylzincs with ah igh degree of stereoretention at the Ca nd the Sa tom. CCR of axially chirala lkenyl sulfoximinesw ith Ni(PPh 3 ) 2 Cl 2 as ap recatalyst and ZnPh 2 does not require salt promotion and is stereoretentive.T he reactionw ith Zn(CH 2 SiMe 3 ) 2 ,h owever,d emands salt promotion and is not stereoretentive. CCR of axially chiral a-methylated alkenyl sulfoximines affordedp ersubstituted axiallyc hiral alkenes with high selectivity.A lkenyl (N-triflyl)sulfoximines engage in as tereoretentive CCR with Grignard reagents and Ni(PPh 3 ) 2 Cl 2 .Ni-Catalyzed and MgBr 2 -promoted CCR of E-configured acyclica lkenyl sulfoximinesa nd aminosulfoxonium salts with ZnPh 2 andZ n(CH 2 SiMe 3 ) 2 is stereoretentivew ith Ni(dppp)Cl 2 and Ni(PPh 3 ) 2 Cl 2 .C CRs of acyclica lkenyls ulfoximinesa nd alkenyl aminosulfoxonium salts, carrying am ethyl groupa tt he a position, take ad ifferent course andg ive alkenyls ulfinamidesu nder stereoretention at the Sa nd C atom.C CR of acyclic, exocyclic, and axially chiral alkenyl sulfoximines has been successfully applied to the stereoselective synthesis of homoallylic alcohols, exocyclic alkenes, and axiallyc hiral alkenes, respectively.

Nickel‐Catalyzed Anionic Cross‐Coupling Reaction of Lithium Sulfonimidoyl Alkylidene Carbenoids With Organolithiums

“…The selectivity of the ACCR of (aR,S)-Li-13 a is lower than that of diastereomer (aS,S)-Li-13 a.R esponsible for the lower selectivity is most likely the competing isomerization of (aR,S)-Li-13 a to the more stable diastereomer (aS,S)-Li-13 a and its respective ACCR. Previously,a lkenyl sulfoximines (E)-H-6 and (aS,S)-H-13 a were found to be subjectt oah ighly stereoselective Ni 0 -catalyzed and Lewis acid-promoted cross-coupling reactionw ith diorganozincs, [6,23,38,39] which most likely proceeds by aK CN catalytic cycle. [3,23] The adaption of this cycle to the ACCR involved (i)ano xidative addition of (aS,S)-Li-13 a to the Ni 0 -catalyst to afford aN i II -complex, (ii)a transmetalation with PhLi, and (iii)areductive elimination to furnish alkenyllithium (aS)-Li-14 a as described in Scheme 5w ith the dottedr ed line.…”

“…The axially chiral lithioalkenyl (N-methyl)sulfoximines (aS,S)-Li-13 a and (aR,S)-Li-13 a,w hich are accessiblet hrough metalation of the corresponding alkenyl sulfoximines( aS,S)-H-13 a and (aR,S)-H-13 a [23] with MeLi, exist as equilibrium mixtures in which the compositiona nd the rate of isomerization are strongly solvent dependent.A lthough the dr of the lithioalkenyl (N-methyl)sulfoximines (aS,S)-Li-13 a and (aR,S)-Li-13 a is 97:3 in diethyl ether at À70 8C( 95:5 at 0 8C) and 97:3 in dimethoxyethane (DME) at À50 8C, it is 33:67 in THF at À70 8C to 0 8C. Lithioalkenyl sulfoximine (aS,S)-Li-13 a is configurationally stable in ether and DME at low temperatures for a prolonged period of time (see the SupportingI nformation for details).…”

“…In furthere xperiments with axially chiral lithioalkenyls ulfoximines, we studied the influence of the substituent at the N atom upon the ACCR. In stark contrast to the (N-methyl)sulfoximine (aS,S)-Li-13 a,t he (N-sulfonyl)sulfoximines (aR,S)-Li-13 b and (aS,S)-Li-13 b (50:50 dr), which were synthesized through metalation of alkenyl sulfoximine (aR,S)-H-13 b [23] with nBuLi, did not undergo an ACCR with PhLi at À75 8Ci nd iethyle ther for 1h in the presence of Ni(PPh 3 ) 2 Cl 2 (5 mol %) (Table 2, entry 5). Quenching the reaction mixture with CF 3 CO 2 Dl ed to ar ecovery of the deuterated sulfoximines (aR,S)-D-13 b and (aS,S)-D-13 b (95 %D )i n5 0:50 dr. Undert hese conditions, already 30 %o ft he (N-methyl)sulfoximine (aS,S)-Li-13 a had been converted to alkenyllithium (aR,S)-Li-14 a (see above).…”

“…Previously,a lkenyl sulfoximines (E)-H-6 and (aS,S)-H-13 a were found to be subjectt oah ighly stereoselective Ni 0 -catalyzed and Lewis acid-promoted cross-coupling reactionw ith diorganozincs, [6,23,38,39] which most likely proceeds by aK CN catalytic cycle. [3,23] The adaption of this cycle to the ACCR involved (i)ano xidative addition of (aS,S)-Li-13 a to the Ni 0 -catalyst to afford aN i II -complex, (ii)a transmetalation with PhLi, and (iii)areductive elimination to furnish alkenyllithium (aS)-Li-14 a as described in Scheme 5w ith the dottedr ed line. Althought he KCN cycle leads, under retention of configuration, to alkenyllithium( aS)-Li-14 a,t he alkenyllithium obtained experimentally in ACCR had the (aR)-configuration, under inversion of configuration.…”

“…The magnesioalkenyl sulfoximines ( E / Z , R )‐Mg‐ 6 (X=Br) (50:50 dr ), which were obtained through metalation of the alkenyl sulfoximine ( E , R )‐H‐ 6 with PhMgBr, engaged in an ACCR with PhMgBr (3 equiv) and Ni(dppp)Cl 2 (dppp=1,3‐bis(diphenylphosphino)propane) (6–10 mol %) in ether at 0 °C for 3 h and gave alkenylmagnesiums ( E / Z )‐Mg‐ 7 a (X=Br), which after quenching with CF 3 CO 2 D furnished the deuterated alkenes ( E / Z )‐D‐ 7 a (93 % D) in 80 % yield and 50:50 dr (Scheme a). A similar ACCR of the lithioalkenyl sulfoximines ( E / Z , R )‐Li‐ 6 (50:50 dr ), which were prepared from ( E , R )‐H‐ 6 upon treatment with MeLi, with PhLi (3 equiv) and Ni(dppp)Cl 2 (10 mol %) in diethyl ether at 0 °C for 3–5 h afforded alkenyllithiums ( E / Z )‐Li‐ 7 a .…”