The Isopropylsulfinyl Group: A Useful Chiral Controller for the Asymmetric Aziridination of Sulfinylimines and the Organocatalytic Allylation of Hydrazones (original) (raw)
Related papers
Organic & Biomolecular Chemistry, 2010
Enantioselective allylation of N-(benzoyl)isobutylhydrazone. General method. SI-8 References. SI-9 1 H-NMR and 13 C-NMR spectra of compounds 4-28. SI-10 HPLC data for the allylation of hydrazone 17 with ligand 28. SI-31 General Methods. All reactions were run under an atmosphere of dry argon using oven-dried glassware and freshly distilled and dried solvents over activated molecula sieves. TLC was performed on Silica Gel GF 254 (Merck) with detection by charring with phosphomolybdic acid/EtOH. For flash chromatography, silica Gel (Merck 230-400 mesh) was used. Columns were eluted with positive air pressure. Chromatographic eluents are given as volume to volume ratios (v/v). NMR spectra were recorded with a Bruker AMX 500 (1 H, 500 MHz) and Bruker Avance DRX 500 (1 H, 500 MHz) spectrometers. Chemical shifts are reported in ppm, and coupling constants are reported in Hz. Routine spectra were referenced to the residual proton or carbon signals of the solvent. High-resolution mass spectra were recorded on a Kratos MS-80RFA 241-MC apparatus. Optical rotations were determined with a Perkin-Elmer 341 polarimeter. The organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. Sulfinyl chlorides were obtained by the method reported by Hermann. 1 Opticaly pure alkanesulfinates were prepared as previously described following DAG methodology. 2 SI-2 Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010 Menthyl p-toluenesulfinate was prepared as described by Solladiè 3 and used as starting material for the synthesis of N-Alkyl-p-toluenesulfinamides 11 and 12 as previously described. 4 General procedure for the synthesis of sulfinamides, 6-9. To a solution of sulfinate ester, 2-5 (12.6 mmol) in THF (50 mL), at-78º C was added a 1M solution of LiHMDS (15 mL, 15 mmol). The reaction was stirred for 1 hour, then MeOH (20 mL) was added, followed by silica gel and the mixture was stirred for 15 min. After evaporation of the solvent, the residue was purified by flash chromatography (AcOEt to AcOEt:MeOH, 9:1). (S)-Ethanesulfinamide, 6. Prepared from (S)-DAG ethanesulfinate, 2, and purified by column chromatography (AcOEt). Obtained in quantitative yield as a colourless oil. [α ] D 20 :-18 (c 0.7, CHCl 3). 1 H-NMR (500 MHz, CDCl 3) δ: 3.86 (brs, 2H), 2,75 (c, 2H), 1,31 (t, J= 5,5 Hz, 3H). 13 C-NMR (125 MHz, CDCl 3) δ: 54.9, 14.5. The enantiomeric excess was determined by HPLC analysis using chiralpak AD column (flow rate 1 mL/min, iPrOH:Hexane 2:98, t R = 49.8 min (6R) and t R = 57.7 min (6S)). (S)-p-Toluenesulfinamide, 7. 5 Prepared from (S)-Menthyl p-toluenesulfinate, 5, and purified by column chromatography (AcOEt:Hexane, from 1:2 to 1:1). Obtained in quantitative yield as a white solid. m.p.: 113º C, [ Lit: m.p.:115º C]. [α ] D 20 :+86 (c 0.2, CHCl 3), [Lit [α ] D 20 : (S) +85 (c 1.0, CHCl 3)]. 1 H-NMR (500 MHz, CDCl 3) δ: 7.62-7.31 (m, 4H), 4.27 (brs, 2H), 2.41 (s, 3H). 13 C-NMR (125 MHz, CDCl 3) δ: 143.4, 141.5, 129.6, 125.3, 29.7. The enantiomeric excess was determined by HPLC analysis using Daicel Chiracel OD column (flow rate 1 mL/min, iPrOH:Hexane 5:95, t R =29.1 min (7R) and t R = 34.3 min (7S)). (S)-Isopropylsulfinamide, 8. 2c Prepared from (S)-DCG isopropylsulfinate, 3, and purified by column chromatography, from AcOEt to AcOEt: MeOH, 9:1). Obtained as a white solid with a low melting point, in quantitative yield. [α ] D 20 :-16 (c 1.1, CHCl 3), Lit 2c [α ] D 20 =-18 (c SI-3
Synthetic Applications of Sulfur-based Chiral Auxiliaries in Asymmetric Syntheses
Journal of the Mexican Chemical Society
This mini-review intends to present one of the themes that has driven my research in developing methodology for the synthesis of natural products and important biologically active molecules. Sulfur-based chiral auxiliaries from aminoacids have been shown to have superior qualities in many cases to other well-known chiral auxiliaries. Some applications of these auxiliaries include acetate aldol reactions, resolution of racemic mixtures, Michael additions, intramolecular thio-Michael/aldol cyclization cascade reactions, and synthesis of natural products, including a new practical and efficient indene-based thiazolidienthione auxiliary.
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.
The Journal of Organic Chemistry, 2011
b S Supporting Information C hiral sulfinyl-containing reagents, such as sulfoxides and sulfinamides, have been recognized as useful tools in the asymmetric synthesis of complex organic molecules. 1 Although the power of chiral sulfinyl reagents in synthetic chemistry has long been recognized, methods for their synthesis have emerged slowly. 1c A few methods have been developed in the past few decades, but a more general and economic method for their synthesis is necessary in order to meet today's need. 2 Primarily, chiral sulfinyl transfer agents only have been used in the synthesis of chiral sulfoxides. Because of their limitation, few methods have been used in the synthesis of chiral sulfinamides. 2aÀf With the pioneering work by Davis et al. 3 for the synthesis of chiral p-toluenesulfinamide (p-TSA) from Anderson's reagent, 4 followed by Ellman et al. 5 for the synthesis of tert-butanesulfinamide (t-BSA), the power of their applications to the asymmetric synthesis of chiral amines was quickly realized. A wide range of natural products as well as many important pharmaceutical agents with chiral amine functionalities have been synthesized using this technology. 5 Because of the limited availability of other sulfinamides, t-BSA and p-TSA have been commonly used in the asymmetric synthesis. 6,7 Many times, sulfinamides with diverse functionalities are needed in order to fine-tune for high stereoselectivity. To meet this need, we developed a unique double displacement method to prepare a variety of both alkane-and arenesulfinamides (Scheme 1). 8 This method is based on the use of a chiral and functionality differentiated oxathiazolidine S-oxide 7a or 7b derived from cis-(R,S)-or (S,R)-amino alcohols, such as N-tosylaminoindanol (6a) or N-tosylnorephedrine (6b). This technology was also employed successfully in the synthesis of a variety of important sulfoxides. However, the relatively expensive aminoindanol and regulated substance norephedrine hindered production of sufinamides on a large scale and in a more economic manner.
Organic Letters, 2011
Preliminary results concerning a conceptually novel route to chiral sulfoxides based on the asymmetric alkylation of sulfenate salts with alkyl halides mediated by a chiral phase-transfer catalyst are described. As a representative example, o-anisyl methyl sulfoxide was produced in 96% yield and with an enantiomeric excess of 58% using commercial cinchonidinium derivative 2a. Enantiopure sulfoxides represent an important class of compounds that find increasing use as chiral auxiliaries or ligands in asymmetric catalysis. 1 Moreover, this sulfur subunit is present in natural products 2 or some biologically significant molecules, 3 the most relevant one being probably the antiulcer agent esomeprazole. Conventional methods for preparing optically active sulfoxides consist of the creation of the sulfurÀoxygen bond by asymmetric oxidation of the parent thioether or formation of the carbonÀsulfur bond by treatment of an organometallic reagent with an enantiopure sulfinyl derivative, namely the Andersen approach, according to an S N 2 mechanism. Despite high synthetic values, these two methods still suffer from limitations. 4,5 Therefore, the development of complementary and conceptually different routes to chiral sulfoxides remains a subject of both relevant synthetic and fundamental interest. Crucial criteria to fulfill include, (1) (a) Fern andez, I.; Khiar, N.
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.