Diastereoselective Synthesis of Ferrocenyl Sulfoximines with Planar and Central Chirality

Abstract

The capability of the sulfonimidoyl moiety to serve as ortho-directing group for the diastereoselective lithiation of enantiopure ferrocenylsulfoximines is demonstrated. (S)-Np-Tolylsulfonyl-S-ferrocenyl-S-tert-butylsulfoximine showed excellent diastereoselectivity concerning planar chirality of the products obtained after quenching of the lithium species with several electrophiles. Various electrophiles (MeI, Me 2 S 2 , Me 3 SiCl, p-anisaldehyde, acetone, n-Bu 3 SnCl, I 2 ) were introduced in yields from 36 to 78%. Only up to 10% of product substituted at both the cyclopentadienyl ring and the phenyl group of the tosyl moiety was isolated as byproduct. The relative configuration of the products was determined by chemical correlation and X-ray crystallographic analysis of (S,R p )-N-p-tolylsulfonyl-S-tert-butyl-S-(2iodoferrocenyl)sulfoximine. Taking into account the structure of the starting material, the ortho-directing effect can be ascribed to the oxygen atom of the sulfoximine.

Reversal of Stereoselectivity in Lithiation of Ferrocenyl‐imidazolones: Epimeric Substrates lead to Planar Chiral Enantiomers

“…Variable temperature 1 H NMR data (300 MHz) of both epimers in DMSO-d 6 at 130 8C did not show any signs of signal coalescence of the ortho Cp hydrogens compared to the room temperature spectra. However, because the ortho Cp hydrogens are inherently nonequivalent, these results alone did not prove the presence of large rotational barriers.…”

“…[1,2] Among these two approaches, diastereoselective procedures employing chiral directing groups have been used more often in part due to the seminal work of Ugi who showed in 1974 that N,N-dimethylferrocenylethylamine 1 provided substituted products in 96:4 diastereomeric ratio (dr) upon lithiation-electrophile quench ( Figure 1). [3] In the ensuing years, many other chiral carbon-, sulfur-or phosphorus-based directing groups, including oxazolines [4] (3), sulfoxides [5] (5), sulfoximines [6] (6), acetals [7] (7), phosphoryls [8,9] (8, 9), hydrazones [10] (10), imidazolines [11] (11), and ferrocenylmethyl-A C H T U N G T R E N N U N G amines [12] (12) have been reported. The observed lithiation stereoselectivity for several of the preceding substrates has been rationalized as originating primarily from avoidance of unfavorable steric interactions between either: (a) the directing group and the ferrocene core, or (b) the directing group and the base used for deprotonation.…”

Ferrocene-derived P,N ligands: synthesis and application in enantioselective catalysis

“…Since the original work of Ugi, several other chiral ortho -directing groups have been developed, such as sulfoxides [31], acetals [32,33], sulfoximines [34], hydrazones [35,36], pyrrolidines [37], imidazolines [38], azepines [39], O-methylephedrine derivatives [40], alcohols [41], phosphine oxides [42] and oxazophospholidines [43]. In addition, oxazolines have been shown by various groups to be excellent ortho -directing groups [44][45][46][47].…”

Iodine(III)‐Mediated Preparations of Nitrogen‐Containing Sulfur Derivatives: Dramatic Influence of the Sulfur Oxidation State

“…The reaction has been extended to sulfides and sulfoxides as nitrene traps to yield sulfimides [12] and sulfoximines, respectively, by Vogt and Muller [13] and by Bolm and co-workers. [14,15] Different phenyliodinanes have been prepared [16±18] by coupling the corresponding sulfonamide with iodosobenzene derivatives in KOH/methanol. The initial step is presumably the solvolysis of the initial iodine reagent.…”