title: Ring-closing metathesis of sulfoximine-substituted N-tethered trienes: modular asymmetric synthesis of medium-ring nitrogen heterocycles.
abstract: A synthesis of sulfoximine-substituted medium-ring nitrogen heterocycles (MRNHs) having a high degree of substitution has been developed. Its key steps are the modular asymmetric synthesis of sulfoximine-substituted N-tethered trienes and their Ru-catalyzed ring-closing metathesis (RCM) reaction. The highly substituted N-tethered trienes were obtained enantio- and diastereopure through 1) the diastereoselective aminoalkylation of sulfoximine-substituted allyltitanium complexes with N-tert-butylsulfonyliminoester, 2) N-allylation of homoallylic N-sulfonyl amines, 3) allylation, hydroxylalkylation, and formylation of α-lithioalkenylsulfoximines, and 4) allylation of α-formylalkenylsulfoximines. The Ru-catalyzed RCM reaction of the sulfoximine-substituted 1,7,10- and 1,7,12-trienes stereoselectively afforded the corresponding nine-, ten-, and eleven-membered MRNHs in good yields. An interesting difference in reactivity was noted in the case of a sulfoximine-substituted 1,7,10-triene and its corresponding 1,10-diene. While the triene readily underwent a RCM reaction, the diene reacted only in the presence of Ti(OiPr)(4) under formation of the corresponding MRNH. The feasibility of a removal of the sulfoximine auxiliary and the N-sulfonyl protecting group from the MRNHs were demonstrated through reduction and cleavage, respectively, of a nine-membered heterocycle, both of which proceeded readily and gave the corresponding cyclic alkene and amine, respectively.
authors.affiliation: Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
authors.forename: Vishal
authors.initials: V
authors.lastname: Mahajan
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gais
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000737:chemistry*; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000588:Amines; D006571:Heterocyclic Compounds; D008717:Methionine Sulfoximine; D012428:Ruthenium; D009584:Nitrogen