Sulfoximine-Directed Single and Double ortho-Lithiation: Stereoselective Rearrangements of o,o′-Dilithiophenylsulfoximines to o,N-Dilithiosulfinylanilines through Anionic Fries Rearrangements of o,o′-Dilithiophenylsulfinamides

• Published in: European Journal of Organic Chemistry 2011-05, Vol.2011 (13), p.2431-2449
• Main Authors: Wessels, Michael, Mahajan, Vishal, Boßhammer, Stephan, Raabe, Gerhard, Gais, Hans-Joachim
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Lithiation; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Rearrangement; Sulfin­amides; Sulfoximines; Sulfur heterocycles
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201100066

Treatment of various phenylsulfoximines with nBuLi (1 equiv.) at –78 °C in THF resulted in single ortho‐lithiations and gave the corresponding o‐lithiosulfoximines. According to NMR spectroscopy, the o‐lithiosulfoximines are generally stable at 0 °C. The o‐lithiosulfoximines were efficiently trapped through deuteration, alkylation, silylation, and phosphanylation. Treatment of cyclic phenylsulfoximines also containing H atoms at their α‐positions with nBuLi (1 equiv.) at –78 °C furnished the o‐lithiosulfoximines with high selectivity, whereas similar treatment at –50 °C to room temperature yielded the corresponding α‐lithiosulfoximines. At elevated temperatures, o‐lithiosulfoximines also possessing α‐H atoms underwent quantitative o,α‐transmetalation to afford the corresponding α‐lithiosulfoximines. Treatment of α,α‐disubstituted cyclic and α,α,α‐trisubstituted acyclic phenylsulfoximines with nBuLi (2 equiv.) at low temperatures led to double ortho‐lithiation and furnished the corresponding o,o′‐dilithiosulfoximines. At elevated temperatures, cyclic o,o′‐dilithiophenylsulfoximines underwent multi‐step rearrangements with formation of o,N‐dilithiated benzothiazepine and benzothiazocine S‐oxide derivatives in high yields. Theacyclic o,o′‐dilithiophenylsulfoximine underwent a similar rearrangement and gave the corresponding o,N‐dilithio‐sulfinylaniline derivative. The rearrangements involve 1) elimination of the lithium sulfinamide from the o,o′‐dilithiosulfoximine, 2) a Li–N addition of the lithium sulfinamide to the o‐lithiobenzyne, and 3) an anionic Fries rearrangement of the o,o′‐dilithiophenylsulfinamide. The rearrangements of the o,o′‐dilithiophenylsulfoximines proceeded with overall retention of configuration at sulfur. Phenylsulfoximines undergo directed single and double ortho‐lithiation with nBuLi. The o,o′‐dilithiosulfoximines undergostereoselective rearrangements to o,N‐dilithiosulfinyl‐anilines. The rearrangements, which proceed with retention of configuration, involve 1) elimination of the lithium sulfinamide, 2) addition of the lithium sulfinamide to o‐lithiobenzyne, and 3) anionic Fries rearrangement.