The use of chiral lithium amides in the desymmetrisation of N-trialkylsilyl dimethyl sulfoximines (original) (raw)
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Tetrahedron, 2005
The sulfoximine group proved to be an excellent ortho-directing group in lithiation reactions. Several electrophiles were used to afford the corresponding ortho-functionalized aryl sulfoximines in good yields. The use of prochiral electrophiles lead to modest to good diastereoselectivities up to 95%. During this study, we observed a side reaction due to a S-de-tert-butylation. After optimization of this S-detert-butylation reaction, the corresponding enantiopure sulfinamides could be obtained in good yields. q Scheme 1. (a) HMDS (5 equiv), 85 8C, 40 min (100%); (b) n-BuLi, THF, 0 8C then CH 3 I, 30 min, 20 8C repeated twice (86%); (c) (1S)-(C)camphorsulfonic acid, acetone. 4
Geminal Bis(sulfoximine)s: Synthesis and Applications in Asymmetric Catalysis
Advanced Synthesis & Catalysis, 2004
A number of C 2-symmetrical geminal bis-(sulfoximine)s have been prepared for the first time and used as ligands in boron-mediated reductions of acetophenone and copper complex-catalyzed 1,4-additions of diethylzinc to 2-cyclohexenone. The copper complex of bis(sulfoximine) 46 was found to be highly active in this type of reaction, furnishing the addition product in nearly quantitative yield even at À 90 8C. From the reaction of bis(sulfoximine) 42 with Cu(OTf) 2 a copper complex was isolated and characterized by X-ray structural analysis. A mixture of SES-Cl and NaN 3 in acetonitrile was found to behave like SES-N 3 in FeCl 2-mediated iminations of sulfoxides, affording the corresponding sulfoximines with complete retention of the sulfur configuration.
Journal of the American Chemical Society, 2014
Several chiral sulfonyl compounds were prepared using the iridium catalyzed asymmetric hydrogenation reaction. Vinylic, allylic and homoallylic sulfone substitutions were investigated, and high enantioselectivity is maintained regardless of the location of the olefin with respect to the sulfone. Impressive stereoselectivity was obtained for dialkyl substitutions, which typically are challenging substrates in the hydrogenation. As expected, the more bulky Z-substrates were hydrogenated slower than the corresponding E isomers, and in slightly lower enantioselectivity.
Asymmetric synthesis of β-hydroxy sulfones by reduction of chiral β-keto sulfones
Tetrahedron: Asymmetry, 1996
Chiral 13-keto sulfones 3 have been prepared from enantiomerically pure sulfinic acids 2 derived from (R)-and (S)-methylbenzylamine. Enantiospecific reduction of these ketosulfones 3 can be achieved using different hydrides affording 13-hydroxy sulfones. Opposite configurations on the newly created stereocenter is obtained with DIBAL-H or LAH as reducing agents.
Tetrahedron: Asymmetry, 2002
Products with three new stereogenic centers were generated via sequential asymmetric dihydroxylation and sulfoxidation of homoallylic sulfides. The non-racemic homoallylic sulfoxides were prepared using chiral, vanadyl-based catalytic system with e.e. of up to 85%. Subsequently, these compounds were dihydroxylated with AD-mix system and gave products of low d.e.s (up to 40%). Recrystallization of l-diastereomers furnished both enantiomerically pure 1-phenyl-4-phenylsulfinylbutane-1,2-diols (X-ray), which are new and useful chiral building blocks. Further oxidation at sulfur produced the corresponding enantiomers of 1-phenyl-4-phenylsulfonylbutane-1,2-diol.
Transition-metal-catalyzed C–N cross-coupling reactions of N-unsubstituted sulfoximines: a review
Journal of Sulfur Chemistry, 2018
In recent years, N-functionalized sulfoximines have attracted the significant attention of medicinal chemists due to their wide spectrum of biological activities. This class of organosulfur compounds has also found a number of applications in agricultural chemistry. In addition to these benefits, sulfoximines are one of the most important and versatile chiral auxiliaries and ligands in asymmetric syntheses. As a result of these, numerous efforts have been devoted to the development of effective strategies towards the synthesis of N-functionalized sulfoximines. An efficient, practical, and versatile strategy for the synthesis of titled compounds involves the transition-metal-catalyzed cross-coupling reactions of easily accessible NH-sulfoximines with various electrophilic partners. In this review, we highlight a number of recent discoveries and advances in this interesting and important research arena. The N-alkylation reactions are discussed first. This is followed by metal-catalyzed N-alkenylation and N-alkynylation reactions. Finally, N-arylation reactions will be covered at the end of the review.
J Org Chem, 1999
Ortho-directed metalation is a useful method to functionalize aromatic ring systems. We report here orthodirected metalations in the π-deficient heterocyclic series (pyridazine, pyrimidine, and pyridine) using an aryl sulfoxide as a chiral ortho-directing group. In aliphatic series, many papers have described asymmetric induction on sp 3 carbon substituted by a chiral sulfoxide during a metalation and reaction with electrophiles process. 1-12 Very few publications have reported metalations of aromatic rings followed by asymmetric inductions during reaction of the lithio compound with a prochiral electrophile; de's in the range 10-83% have been obtained. 13-17 The only reference with sulfur derivatives is that of H. Takahashi 18 who obtained up to 82% de using chiral sulfonamides. Our knowledge about sulfur derivatives as directing groups for metalations of diazines and our successful metalations of racemic sulfoxides 19,20 prompted us to study a p-tolylsulfinyl group as a chiral directing agent. Sulfoxides 21,22 have not been used previously as asymmetric directing groups for the enantioselective "orthodirected metalation-reaction with electrophile sequence" in the aromatic series. The synthesis of enantiomerically pure sulfinyl pyridazines was unknown. Asymmetric oxidations of 3-phenyl or 3-(methylthio)-6-methoxypyridazine and 2-phenylor-(methylthio)pyrazine by Sharpless or Kagan's method 23-31 and using oxaziridines 32-39 failed. On the other hand, Andersen's method 40-42 using organometallics and chiral menthyl p-toluenesulfinates, which are commercially available, gave excellent enantiomeric excesses after extensive studies (Schemes 1-3). Synthesis of products 3a and 3b (Scheme 1) could be achieved as follows. The preparation of 2 was carried out in the usual conditions. The second step from 2 to 3a or 3b was successful only if a reverse addition was used; i.e., the reaction mixture containing the lithium derivatives was poured into a solution of the menthyl p-toluenesulfinate in THF. Under these conditions, 3a and 3b were obtained
Metalated 2-Alkenylsulfoximines: Efficient Solutions for Asymmetric d3-Synthons
Journal of the American Chemical Society, 1996
By starting from the 4,5-dihydro-1,2λ 6 ,3-oxathiazole 2-oxides 5 and 6 or their enantiomers, a number of enantiopure acyclic and cyclic 2-alkenyl sulfoximines have been prepared. After deprotonation with n-BuLi and transmetalation with chlorotris(isopropoxy)titanium chloride, these sulfoximines can be γ-hydroxyalkylated to the corresponding γ-hydroxy vinyl sulfoximines with high diastereomeric excesses (g95% de) irrespective of the nature of the added aldehyde. The cyclopentenyl-and cyclohexenylsulfoximines 50a/51a and 50b/51b are demonstrated as the first examples of highly enantioselective solutions for cyclic d 3-synthons. From the X-ray structures of 18e, 21, 59, and 62, it can be deduced that the S S /R S-configured sulfoximines attack the aldehydes nearly exclusively from their Re/Si faces, respectively. A remarkable property of these systems is that this stereochemical interrelation holds also for reactions with chiral aldehydes (reagent control), although here the achievable stereocontrol depends on the relative configuration of the stereogenic centers in the auxiliary. This is especially true for the cyclohexenylsulfoximines 50b and 51b, which require the same absolute configuration at both the sulfur atom and the carbon atom in the side chain of the amino acid based auxiliary. In the case of this intramolecular matched situation, the stereochemical preferences of the chiral aldehyde can be overcompensated nearly completely. This mutual reinforcement of the two stereogenic centers in the sulfoximine moiety accounts for the high degree of reagent control (g94% de in the acyclic series, g95% de with the five-membered ring systems, and g97% de with the cyclohexenylsulfoximines) achievable with these 2-alkenylsulfoximines.