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Highly Efficient Camphor-Derived Oxaziridines for the Asymmetric

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Highly Efficient Camphor-Derived Oxaziridines for the Asymmetric Highly Efficient Camphor-Derived Oxaziridines for the Asymmetric Oxidation of Sulfides to Chiral Sulfoxides Vassilios Meladinis, Uwe Verfürth, and Rudolf Herrmann* Organisch-Chemisches Institut der Technischen Universität München, Lichtenbergstraße 4, D-8046 Garching, Bundesrepublik Deutschland Dedicated to Prof. Dr. Ivar Ugi on the occasion o f his 60th birthday Z. Naturforsch. 45b, 1689- 1694 (1990); received May 18, 1990 Asymmetric Oxidation, N-Sulfonyl-oxaziridines, Chiral Sulfoxides, Camphorsulfonic Acid Chiral N-sulfonyl-oxaziridines derived from 8 -camphorsulfonic acid and fenchone have been evaluated as asymmetric oxidizing agents for the conversion of sulfides to chiral sulf­ oxides. There is no correlation between the redox potentials nor the lvO NMR chemical shifts of the oxaziridines and their relative oxidation rates, nor with the enantiomeric excesses achieved, indicating that steric effects are responsible for their behaviour. The results are con­ sistent with an attack of one sulfur lone pair at the oxaziridine oxygen in such a way that both sulfur lone pairs lie in the plane of the oxaziridine ring. The most efficient oxaziridines, the camphorlactone-sulfonyloxaziridine [(4aS,9aR)-10,10-dimethyl-6,7-dihydro-4H-4a,7-meth- ano-oxazirino[3,2-j]oxepino[3,4-c]isothiazol-9(5 H)-one 3,3-dioxide] and the 3-endo-bromo- camphorsulfonyloxaziridine [(4aS,8 S ,8 aR)-8-bromo-9,9-dimethyl-5,6,7,8-tetrahydro-4 H- 4a,7-methano-oxazirino-2,l-benzisothiazole 3,3-dioxide] allow the preparation of chiral sul­ foxides with up to 85% enantiomeric excess. Introduction crowded oxaziridines activated by an electron- Chiral sulfoxides play a prominent role among withdrawing sulfonyl group at nitrogen give the the chiral auxiliaries used for the synthesis of enan- best results. This concept is ideally realized in the tiomerically pure compounds, such as natural bicyclic system of camphor, which is easily deriva- products [1], and remarkable success has been tized to form many useful chiral auxiliaries [12]. achieved [2], particularly for terpenes. The classi­ The main advantage is that most reactions at the cal Andersen synthesis of such chiral sulfoxides camphor skeleton are highly stereoselective, and from diastereomerically pure sulfinates with Gri- only few procedures involve the separation of dia- gnard or lithium reagents [3] can be applied only to stereoisomers. We have prepared some new oxa­ a limited number of sulfoxides, and thus, the oxi­ ziridines derived from 8-camphorsulfonic acid dation of sulfides to chiral sulfoxides, as the most which are modified in the position 3 of the cam­ direct access, remains a challenging task. Among phor molecule, and wish to report here on the the methods available, the microbiological proce­ results in the oxidation of sulfides to chiral sulf­ dures [4] allow the preparation of almost enan- oxides. tiomerically pure sulfoxides of special types. The more general chemical methods include catalytic Results and Discussion oxidations, using bovine serum albumin or fla­ vines [5], and Kagan’s modification of the Sharp- We have reported on the synthesis of the cam­ less oxidation (titanium/tartrate catalyst) [6] seems phor-derived oxaziridines 2 [9], 3 [10], 4, 5, 6, 7, to be well suited for most purposes. Non-catalytic and 8 [13], included in this study. The preparation processes are of interest only where they apply ex­ of the fenchone-derived oxaziridine 9 will be re­ ceedingly mild reaction conditions. This is the case ported elsewhere. The oxidations were performed with chiral oxaziridines [7], A variety of such oxi­ in CC14 at standard concentrations (0.05 mol/1 for dants has already been prepared for this purpose both oxaziridine and sulfide), as this is the solvent [8-11], and it was found that rigid and sterically which gives the highest enantiomeric excesses in almost all cases [9, 11]. The oxaziridines are not * Reprint requests to Dr. R. Herrmann. always completely soluble, which means that long­ Verlag der Zeitschrift für Naturforschung, D-7400 Tübingen er reaction times are required, especially in the case 0932 - 0776/90/1200 -1689/$ 01.00/0 of the camphorlactone-sulfonyloxaziridine 3. 1690 V. M eladinis et al. ■ Highly Efficient Camphor-Derived Oxaziridines parameters, to see if it might be possible to predict the reactivity and selectivity of new oxaziridines. We therefore measured the redox potentials and the pO NMR spectra of some oxaziridines. These data are listed in Table I. As no l70 NMR data have been reported for oxaziridines up to now, we have also included the racemic oxaziridines 10, 11, and 12, for comparison. It is interesting to note that all oxaziridines give signals between -18 and -20 ppm, a very narrow range compared with the large differences ob­ served between compounds of the same type, e.g. methanol (-37 ppm) and ethanol ( + 6 ppm). It seems that the geometry of the three-membered ring mainly governs the chemical shifts, and not the influence of the electron donor or acceptor ca­ pacity of the substituents. It is very striking that the strongly electron-withdrawing sulfonyl substi­ tuents at nitrogen do not have significant effects, nor does the structure of the carbon substituents. The linewidths (50- 160 Hz) are normal for the ob­ servation temperature (37 C). This narrow range of the chemical shifts excludes reliable correlations with reaction rates or enantioselectivity. The l70 chemical shifts of other oxygens in the molecules lie in the range expected for this functional groups [20 ]. As judged from the redox potentials, the elec- First, we were interested in correlations of reac- tron acceptor capacity of the oxaziridines increas- tion rates and enantioselectivities of the oxidation es in the direction 3<6< 1<2<9<7<8<4. of sulfides to chiral sulfoxides with other physical The reduction waves of all oxaziridines are irrever- Table I. Redox properties 3 and l70 NMR data of some oxaziridines. Compound Eped (V ) ö (l70 ) (in acetone-d6)b Remarks C-N-O others 1 -2.30 -18.8 (50 Hz) 175.3, 178.3 (S02) [8] 2 -2 .2 6 -- [9] 3 -2.40 -18.1 (160 Hz) 158.8 (-0-), 180.9, 183.0 (SO,), [ 1 0 ] 538.8 (C = 0 ) 4 -1 .9 7 - - [13] 6 -2 .3 6 - - [13] 7 -2 .1 7 -- [13] 8 -1 .9 9 —— [13]; very slow oxidation of sulfides 9 -2 .2 5 —— very slow oxidation of sulfides 10 - -1 8 .4 (6 0 Hz) 138.2, 144.0 (SO,) [14]; racemic 11 - -19.9(120 Hz) NO^ overlaps with acetone [15]; racemic 12 - -19.5 (130 Hz) NO: overlaps with acetone [15]; racemic a Peak potential of the irreversible cathodic wave, in 0.1 M NBu4BF4 in tetrahydrofuran, relative to internal FcH/ FcH+; b chemical shifts relative to internal (Me-d 3)-,CpO (S = 569 ppm); linewidth in brackets. V. M eladinis et al. ■ Highly Efficient Camphor-Derived Oxaziridines 1691 sible, which points to a chemical reaction occur­ oxaziridine has to be tested individually for its effi­ ring after the initial one-electron reduction. It is ciency as chiral oxidation reagent, as no predic­ not obvious what this reaction might be. The time tions can be made from other data. It seems that necessary for complete conversion of the sulfide this efficiency is mainly determined by steric (Table II) is used as a rough measure for the reac­ effects. tion rates; the low solubility of some oxaziridines The differing steric requirements of the substi­ does not allow to determine exact rates. For the tuents in the position 3 of the camphor skeleton oxidation of methyl phenyl sulfide, the reactivity lead to a different behaviour of the oxaziridines in increases in the direction 7 — 6<3<4<5<§2. 8 the oxidation of sulfides. This is illustrated for the and 9 react very slowly with sulfides, and only very oxidation of methyl phenyl sulfide in Schemes low yields of sulfoxide were obtained with these 2 -4 . oxaziridines. They are therefore not included in For the oxidation of sulfides by oxaziridines, it Table II. is generally agreed that the approach of the sulfur As for the enantioselectivities of the same oxida­ to be oxidized to the oxygen of the oxaziridine tion, we have found an increasing efficiency in the occurs in such a way that both lone pairs of sulfur direction 1 — 5< 6< 7< 2 — 4<3. No correla­ lie in the plane of the three-membered ring. It then tion with the reaction rates nor the redox poten­ depends on the space available on the left or right tials could be found, which means that any new side of the oxaziridine group how the larger or Table II. Oxidation of sulfides R '-S -R 2 to chiral sulfoxides with oxaziridines11. Entry Oxaziridine R 1 R2 Time [h] Yield [%] Mb2b e.e. Configuration Ref. [%] 1 2 Ph Me 1 80 - 8 6 59 S [9, 16] 2 3 Ph Me 6 8 85 -1 1 5 79 S 3 4 Ph Me 48 55 -8 4 57 S 4 5 Ph Me 24 65 + 4.0 3 R 5 6 Ph Me 72 60 + 14 9 R 6 7 Ph Me 72 63 -3 6 24 S 7 2 4-M e-P h Me 2 0 79 -7 9 56 S [9, 17] 8 3 4-M e-P h Me 70 90 - 1 0 2 72 s 9 2 4-M e-P h Et 3 8 6 -1 1 7 61 s [9, 17] 10 3 4-M e-P h Et 72 95 -1 4 5 76 s 11 4 4-M e-P h Et 48 49 -1 6 2 85 s 12 2 4-Me-Ph Ph 24 8 8 -7 .0 27 s [9, 17] 13 3 4-M e-P h Ph 72 85 -9 .0 35 s 14 3 2-M e-P h Ph 72 8 8 -8 0 ?° 9 - 15 2 cyclohexyl Ph 3 79 - 9 7 d 49 9 [9, 18] 16 3 cyclohexyl Ph 72 95 - 132d 67 9 17 2 P h -C H , Et 2 0 79 + 17 32 R [9, 19] 18 3 Ph-CH^ Et 70 80 + 24 45 R 19 4 P h -C H ' Et 48 51 + 25 47 R 2 0 2 Ph-CH^ Ph 3 6 8 — 9 1 e 36 s [4, 9] 21 4 P h -C H i Ph 48 45 94° 37 s ?c 2 2 2 2,4,6-Me,Ph Ph 48 65 197 9 [9] 23 3 2,4,6-Me,Ph Ph 160 70 -1 9 9 ?c 9 24 2 C H ,=C H Ph 4 75 — 12 0 e 39 s [6 .
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