Synthesis of a Six-Membered-Ring (2R)-10a-Homobornane-10a,2-sultam and Structural Comparison with Oppolzer's, Lang's, and King's Sultams (original) (raw)
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The Journal of Organic Chemistry, 1987
Reaction of (trimethylsily1)methanesulfonyl chloride (6a) or-sulfonic anhydride (6b) with cesium fluoride in the presence of cyclopentadiene affords 2-thiabicyclo[ 2.2.lIhept-5-ene 2,a-dioxide (4) by way of sulfene CH2=S02. Similar reaction of (trimethylsily1)methanesulfinyl chloride (7) gave the unstable 2-thiabicyclo[2.2.1] hept-5-ene endo-2-oxide (3) via the intermediacy of sulfine CH2=S0. Compound 3 can be oxidized to 4 and reduced to 2-thiabicyclo[2.2.1]hept-5-ene (1) and the latter oxidized to the stable 2-thiabicyclo[2.2.1]hept-5-ene exo-2-oxide (2). Fluorodesilylation of 1-(trimethylsily1)propanesulfonic anhydride (8) in the presence of cyclopentadiene gave a 77/23 ratio of endo/exo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene 2,2-dioxide (9a/b) by way of propanethial S,S-dioxide. The structure of the major isomer 9a was established by an X-ray structure of the corresponding exo-epoxide lla, formed from 9a by oxidation. Reaction of 4 with n-butyllithium followed by ethyl iodide gave a compound identical with minor isomer 9b. Reaction of propanethial S-oxide with cyclopentadiene gave unstable endo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene endo-5-oxide (loa). The structure of loa was established by oxidation to sulfone 9a, by reduction and reoxidation to a stable exo-5-oxide lob, by its facile [2,3] sigmatropic rearrangement to exo-4-ethyl-2-oxa-3-thiabicyclo[3.3.0]oct-7-ene (14c), and by NMR spectroscopic methods. Compound 14c was characterized by NMR spectroscopy and by ita reactions. Oxidation of 14c gave the endolexo-3-oxides 15c/15c' and the 3,3-dioxide 16c. Reaction of 14c with phenyllithium gave alcohol 17c, which was desulfurized and oxidized to 5-propyl-2-cyclopentenone or was oxidized at both carbon and sulfur to give (E)-5-propylidene-2-cyclopentenone 21c on gentle warming. Reaction of 14c with tert-butyl alcohol gave exo-6-tert-butoxy-exo-3-ethyl-syn-7hydroxy-2-thiabicyclo[2.2.l]heptane (24), characterized by further oxidation to crystalline hydroxy sulfone 25 and keto sulfone 26. Mechanisms are proposed for the above series of reactions. (1) (a) The Chemistry of Sulfines. 13. (b) Part 12 Block, E.; Ahmad, S.
2-Sulfinyl Oxetanes: Synthesis, Stability and Reactivity
Synlett, 2015
All non-aqueous reactions were carried out under an inert atmosphere (argon) with oven-dried (160 ºC) or flame dried glassware using standard techniques. Anhydrous solvents were obtained by filtration through drying columns (THF, Et 2 O, CH 2 Cl 2 , PhMe) or obtained from commercial suppliers and used without further purification (DMF). H 2 O was distilled before use. Flash column chromatography was performed using 230-400 mesh silica, with the indicated solvent system according to standard techniques. Analytical thin-layer chromatography (TLC) was performed on precoated, glass-backed silica gel plates. Visualization of the developed chromatogram was performed by UV absorbance (254 nm), aqueous potassium permanganate stain or PMA (phosphomolybdic acid). Infrared spectra were recorded using a Perkin-Elmer spectrum 100 FT-IR Spectrometer and the absorbencies were reported in wavenumbers (cm-1). Nuclear magnetic resonance spectra were recorded on a Bruker AV 400 (400 MHz) or AV 500 (500 MHz) spectrometer. Data were reported as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, br = broad), coupling constant in Hz and assignment. Chemical shifts are reported in parts per million from tetramethylsilane with the solvent resonance as an internal standard (1 H NMR spectra: CDCl 3 : δ = 7.27 ppm, (CD 3) 2 CO: δ = 2.05 ppm, CD 3 OD: δ = 3.31 ppm, (CD 3) 2 SO: δ = 2.50 ppm. 13 C NMR spectra: CDCl 3 : δ = 77.00 ppm, (CD 3) 2 CO: δ = 29.84, 206.26 ppm, CD 3 OD: δ = 49.00 ppm, (CD 3) 2 SO: δ = 39.52 ppm) or using chloroform with 1% tetramethylsilane as the internal standard. 13 C NMR spectra were recorded with complete proton decoupling. 19 F NMR spectra were recorded with complete proton decoupling. Chemical shifts are reported in parts per million referenced to the standard monofluorobenzene: −113.5 ppm. Assignments of 1 H and 13 C spectra were made by the analysis of δ/J values and COSY, HSQC and HMBC experiments as appropriate. High resolution mass spectrometry were recorded on VG Platform II, Waters Xevo G2-S, VG Autospec or Thermofisher LTQ Orbitrap XL spectrometers. Melting points are uncorrected Reagents: For the preparation of LDA or LiHMDS solutions, diisopropylamine or hexamethyldisilazane were distilled over potassium hydroxide immediately before use. Unless otherwise stated mCPBA was washed prior to use: dissolved in CH 2 Cl 2 , washed with a phosphate buffer (pH 7.5) and dried (MgSO 4) then the solvent removed under reduced pressure. All commercially available organometallic solutions were titrated against salicylaldehyde phenylhydrazone. i All other commercially available reagents were used without further purification. Preparation of a 0.61M solution of LiHMDS: A solution of HMDS (1.27 ml, 6.0 mmol) in THF (5.38 mL) was cooled to-78 ºC for 10 min then nBuLi (2.35 mL, 5.49 mmol, 2.3 M in hexane) was added dropwise. The solution was stirred at-78 ºC for 30 min then warmed to 0 ºC for 30 min prior to immediate use. General Procedure for the preparation of a 1 M solution of LDA: A solution of diisopropylamine (0.92 mL, 6.60 mmol) in THF (2.68 mL) was cooled to-78 ºC for 10 min then nBuLi (2.40 mL, 6.00 mmol, 2.5 M in hexane) was added dropwise. Solution stirred at-78 ºC for 1 h prior to use. Compound Handling/Purification/Storage: All synthetic intermediates were stored under argon at-20 ºC for short periods of time. Instability of sulfoxide compounds meant that in some cases appropriate molecular ions (HRMS) could not be obtained.
Novel cysteic acid s-amides substituted in the sulfonamide function. Synthesis and modifications
2012
In the present work we reported the synthesis of several analogues 5a-e of cysteic acid S-amides with substituted sulfonamide function, where fully protected D, L-cysteic acid S-chlorides were treated with the required aliphatic amines to give a series of new derivatives which could be considered as structural sulfoanalogues of leucine, isoleucine and norleucine, respectively. We presented here new method for preparation of D, L-cysteic acid S-chlorides.
Recent Advances and Perspectives in the Chemistry of Sulfenic Acids
Current Organic Chemistry, 2007
This review (56 references) provides a comprehensive survey of the literature on sulfenic acid chemistry from 1990 through June 2006, focusing the attention on salient aspects of their structures and involvement in organic processes. Even if the majority of known sulfenic acids cannot be isolated, some stable ones have been obtained, and their study helped dramatically the comprehension of chemical and physical properties of all sulfenic acids and indirectly of the role that Cys-SOHs play in protein biochemistry. Many papers have been published in the last fifteen years about the sulfenic acid intermediacy in organic chemistry. Once generated, they can be involved in intra-and intermolecular additions to unsaturated molecules. Few examples of sulfenic acid addition to double bonds have been recently described and most of them are intramolecular processes, whereas the addition of enantiopure sulfenic acids onto carbon-carbon triple bonds has been widely exploited in the synthesis of vinyl sulfoxides to be used in many stereoselective transformations. The thermic -elimination from sulfinyl precursors is a way to generate sulfenic acids but it has been also used for removing the sulfinyl moiety from organic molecules and forming double bonds with controlled stereochemistry. Some significant applications of extrusion processes are also described in the present review.
Synthesis of sulphonic acids and sultam derivatives
Archives of Pharmacal Research, 1990
DReaction of propane-l,3-sultone with amines gave N-substituted aminosulphonic acids 2a-i. Dehydration of 2a-c with POC13 gave the corresponding sultams 3a-c. Propane-l,3-sultone 1 reacted with tertury amines to give the betaiene salts 4-11.2,4-Dimethyl-l,3-butadiene-1,4-sultone 12 condensed with amines to give N-substituted-2,4-dimethyl-1,3-butadiene-l,4-sultams 13a and 13b. The reaction of 3a, 13a with hydrazine hydrate gave acid hydrazides 3d or 13c. Compounds 3d, 13c reacted with isocyanates to yield urea derivatives 14a-e, 15a-c.
Access to a Wide Range of Sultams by Cyclodialkylation of α-Substituted Methanesulfonanilides
European Journal of Organic Chemistry, 2012
A wide range of five-and six-membered sultams bearing an α-ethoxycarbonyl-α-methyl substituent or an α-aryl group (17 examples) were synthesized by the cyclodialkylation of αsubstituted methanesulfonanilides with α,ω-dihaloalkanes in the presence of K 2 CO 3 or under phase-transfer catalysis (PTC) conditions. Upon treatment with K 2 CO 3 in N,N-dimethylformamide (DMF) or NaH in dimethyl sulfoxide [a
ChemInform Abstract: Recent Advances in the Synthesis of Sulfonic Acids
ChemInform, 2002
This review article surveys recent achievements in the preparation and biological properties evaluation of fluorinated aminophosphonates and aminophosphonic acids. Recently, in view of various important biological applications of the fluorinated aminophosphonic acid derivatives, the development of suitable synthetic methodologies for their preparation in racemic and in optically pure form has been a topic of great interest. Considerable progress has been made in asymmetric synthesis of fluorinated acyclic aminophosphonates and aminophosphonic acids using catalytic enantioselective reduction of fluorinated a-iminophosphonates, catalytic enantioselective addition of alkyl phosphites to fluorinated imines, and diastereoselective addition of alkyl phosphites to chiral fluorinated imines. A new efficient access to CF 3substituted cyclic a-aminophosphonates has been developed based on metal-catalyzed carbene transfer reactions with diethyl 1-diazo-2,2,2-trifluoroethylphosphonate. New processes, e.g. enantioselective alkynylation and nucleophilic aromatic substitution involving fluorinated substrates are also considered.
Crystals
The search for a simple and efficient method for the synthesis of sulfonamide and sulfonate derivatives under mild and eco-friendly conditions is of continuing interest. Sulfonyl chlorides are still the best choice as starting materials for the preparation of target products. Here, we report a simple, efficient and eco-friendly method for the synthesis of sulfonamide and sulfonate carboxylic acid derivatives under green conditions using water and sodium carbonate as HCl scavengers to produce the products with high yields and purities. Two derivatives, 4-(tosyloxy)benzoic acid (5a) and 4-((4-methylphenyl)sulfonamido)benzoic acid (5b), were reacted with 2-morpholinoethan-1-amine under green conditions, where OxymaPure/diisopropylcarbodiimide (DIC) was used as a coupling reagent and 2-MeTHF as a solvent to give the target product with high yield and purity. nuclear magnetic resonance (NMR) and elemental analysis confirmed the structures of all obtained products. X-ray crystallography c...
ChemInform, 2005
All solvents were distilled prior to use: THF and Et 2 O from Na and benzophenone; DMF, CH 2 Cl 2 , and toluene from P 2 O 5. Solvent after reactions and extractions were evaporated in a rotatory evaporator under reduced pressure. Liquid/solid flash chromatography (FC): columns of silica gel (0.040-0.63 µm, silica gel 60,240-400 mesh). Thin layer chromatography (TLC) for reaction monitoring; detection by UV light. Pancaldi reagent ((NH 4) 6 MoO 4 , Ce(SO 4) 2 , H 2 SO 4 , H 2 O), or KMnO 4. M.p.: uncorrected; IR Spectra : spectrometer; υ in cm-1. 1 H-NMR Spectra: 400 MHz spectrometer; δ(H) in ppm rel.to internal Me 4 Si (= 0.00 ppm) or to the solvent's residual 1 H-signal (CH-Cl 3 , δ(H) 7.27; C 6 HD 5 , δ(H) 7.16; CHD 2 COCD 3 , δ(H) 1.95; CD 2 HCN, δ(H) 2.50; CHD 2 SOCD 3 , δ(H) 2.50, CH 2 OD, δ(H) 3.31) as internal reference, all 1 H-signal assignments were confirmed by double irradiation experiments or by 2D COSY-DQF or COSY-45 spectra. 13 C-NMR Spectra: same instruments as above (101.61MHz); δ(C) in ppm rel. to internal Me 4 Si (= 0.00 ppm) or to solvents 13 C-signal (CDCl 3 , C 6 D 6 , δ(C) 128.4; (CD 3) 2 CO, δ(C) 29.8; CD 3 CN, δ(C) 1.3; (CD 3) 2 SO, δ(C) 39.5, CD 3 OD, δ(C) 49.2) as internal reference; coupling constants J in Hz (±0.5 Hz). Ms, chemical ionization (NH 3) mode m/z amu [% relative base peak(100%) ] General Procedure 1 (Table 1, entries 1-4) for the three-component syntheses of sulfonamides. (t-Bu)Me 2 SiOSO 2 CF 3 (37 mg, 0.14 mmol, 0.05 equiv) in anh. CH 2 Cl 2 (2 mL) was degassed by freeze-thaw cycles on the vacuum line. SO 2 (1.2 mL, 27.4 mmol, 10 equiv), dried by passing through a column packed with phosphorus pentoxide and aluminium oxide, was transferred on the vacuum line to the CH 2 Cl 2 solution frozen at-196 °C. The mixture was allowed to melt and to warm to-78 °C. After 30 min at this temperature the enoxysilane 2a (2.74 mmol, 1 equiv) in CH 2 Cl 2 (2 mL) was added slowly. The mixture was stirred at during 2 h at-78 °C. Then the excess of SO 2 and the solvent were evaporated under reduced pressure (10-1 Torr) to dryness (ca. 1h), while temperature slowly reached 20 °C. Halogenating agent (Br 2 , 0.15 mL, 3.01 mmol, 1.1 equiv) was added at-20 °C. After 1 h at this temperature, the mixture was transferred to a solution of the amine (3.29 mmol, 1.2 equiv) in 2 mL CH 2 Cl 2 in presence of Et 3 N (0.45 mL, 3.29 mmol, 1.2 equiv) under Ar atmosphere. The mixture was finally stirred at this temperature for 2 h, and poured into ice-water (20 mL) and extracted with CH 2 Cl 2 (15 mL, 3 times). The combined organic extracts were washed with brine (20 SM3 mL), dried (Na 2 SO 4) and the solvent eliminated under reduced pressure under reflux. Purification by FC. General Procedure 2. (Table 1, entries 5-9 and 11-14) for the three component syntheses of sulfonamides. (t-Bu)Me 2 SiOSO 2 CF 3 (37 mg, 0.14 mmol, 0.05 equiv) in anh. CH 3 CN (2 mL) was degassed by freeze-thaw cycles on the vacuum line. SO 2 (1.8 mL, 41.1 mmol, 15 equiv) dried by passing through a column packed with phosphorus pentoxide and aluminium oxide, was transferred on the vacuum line to the CH 3 CN solution frozen at-196 °C. The mixture was allowed to melt and to warm to-78 °C. After 30 min at this temperature the enoxysilanes 2b, 2c or 2e (2.74 mmol, 1 equiv) in CH 3 CN (2 mL) were added slowly. The mixture was stirred at-78°C during 5-7 h. Then, the excess of SO 2 and the solvent were evaporated under reduced pressure (10-1 Torr) to dryness (ca. 1h), while temperature slowly reached 20 °C. Halogenating agent (Br 2 , 0.15 mL, 3.01 mmol, 1.1 equiv) was added at-20 °C. After 1h at this temperature, the mixture was transferred into a solution of the amines (3.29 mmol, 1.2 equiv) in 3 mL pyridine or in 2 mL CH 2 Cl 2 in presence of Et 3 N (0.45 mL, 3.29 mmol, 1.2 equiv) under Ar atmosphere. The mixture was finally stirred at this temperature for 2 h, and poured into ice-water (20 mL) and extracted with CH 2 Cl 2 (15 mL, 3 times). When pyridine was used 20 mL of ether were added and the mixture was washed with a saturated aqueous solution of CuSO 4 (30 mL, 3 times). Combined organic extracts were washed with brine (20 mL), dried (Na 2 SO 4) and the solvent eliminated under reduced pressure under reflux. Purification by FC. General Procedure 3 (Table 1, entry 10) for sulfonamides preparation. (t-Bu)Me 2 SiOSO 2 CF 3 (37 mg, 0.14 mmol, 0.05 equiv) in anh. CH 3 CN (2 mL) was degassed by freeze-thaw cycles on the vacuum line. SO 2 (1.8 mL, 41.1 mmol, 15 equiv), dried by passing through a column packed with phosphorus pentoxide and aluminium oxide, was transferred on the vacuum line to the CH 3 CN solution frozen at-196 °C. The mixture was allowed to melt and to warm to-78 °C. After 30 min at this temperature the enoxysilane 2d (2.74 mmol, 1 equiv) in CH 3 CN (2 mL) was added slowly. The mixture was stirred at-78°C 3 h. Then the excess of SO 2 and the solvent were evaporated under reduced pressure (10-1 Torr) to dryness (ca. 1h), while temperature slowly reached 20 °C.