 | Acta Crystallographica Section E Acta Crystallographica Section E CRYSTALLOGRAPHIC COMMUNICATIONS |
journal menu
organic compounds
| CRYSTALLOGRAPHIC COMMUNICATIONS |
access(2S)-2-[(2S*,5R*,6R*)-5,6-Dimethoxy-5,6-dimethyl-1,4-dioxan-2-yl]-1-[(S)-1,1-dimethylethylsulfonyl]aziridine
aSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, England, and bDepartment of Chemistry, University of South Alabama, Mobile, AL 36688-0002, USA
*Correspondence e-mail: dforbes@southalabama.edu
The reaction of a sulfur ylide with a chiral non-racemic sulfinyl imine afforded the desired aziridine in excellent yield and subsequent oxidation of the sulfinyl moiety dissolved in anhydrous dichloromethane using a 75% aqueous solution of 3-chloroperoxybenzoic acid afforded the title compound, C14H27NO6S. The configuration of the newly formed stereogenic center at the point of attachment of the 1,4-dioxane ring to the aziridine ring is S. The configurations of the pre-existing sites 2-, 5-, and 6-positions of the 1,4-dioxane ring prior to reaction of sulfinyl imine with the sulfur ylide are S, R, and R, respectively. The C—N bond lengths of the aziridine are 1.478 (2) and 1.486 (2) Å.
Related literature
For the first synthesis of the title compound, see: Forbes et al. (2009![[Forbes, D. C., Bettigeri, S. V. & Pischek, S. C. (2009). Chem. Commun. pp. 1882-1884.]](../../../../../../logos/arrows/e_arr.gif "Forbes, D. C., Bettigeri, S. V. & Pischek, S. C. (2009). Chem. Commun. pp. 1882-1884.")
). For the use of sulfinyl in the preparation of aziridines, see: Forbes et al. (2009); Chigboh et al. (2008); Morton et al. (2006). For a review on the use sulfur ylide technologies in the preparation of three-membered rings, see: McGarrigle et al. (2007). For the use of tert-butyl sulfinyl groups as stereodiscriminating groups, see: Ellman et al. (2002); Wakayama & Ellman (2009). For the use of three-carbon building blocks in the assembly of systems of medicinal significance, specifically HIV protease inhibitors, see: Izawa & Onishi (2006); Honda et al. (2004).
![[Scheme 1]](hb5738scheme1.gif)
Experimental
Crystal data
|
Data collection
Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).
Supporting information
contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536810048816/hb5738sup1.cif
Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810048816/hb5738Isup2.hkl
(2S)-1-[S(S*)-(1,1-dimethylethyl)sulfinyl]-2-[(2S*,5R*, 6R*)-2-(5,6-dimethoxy- 5,6-dimethyl-1,4-dioxacyclohexyl)]aziridine
To a 60% solution of sodium hydride (203 mg, 5.03 mmol) in anhydrous dimethylsulfoxide (6 ml) was added trimethylsulfonium iodide (1.025 g, 5.03 mmol). This was stirred until the cloudy mixture went clear. At this point a solution of ([S(S), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl) methylene]-2-propanesulfinamide (515 mg, 0.167 mmol) in anhydrous dimethylsulfoxide (4 ml) was added dropwise to the mixture and the solution was stirred at room temperature for 30 minutes. Once complete, ice-cold brine (5 ml) was added, and the reaction stirred for 5 minutes. The resulting mixture was filtered through a pad of Celite, and the solution extracted with ethyl acetate (3x5 ml), and concentrated under reduced pressure. The residue was partitioned between 1:1 petroleum ether/ethyl acetate and water, and the organic fraction dried over anhydrous sodium sulfate. Purification by over silica gel (eluting with 5:1 petroleum ether/ethyl acetate) afforded the title compound (108 mg, 20% yield). [α]D -94 (c 1/2, CHCl3); νmax (CHCl3)/cm-1 3010, 2835, 1521, 1475, 1425, 1377, 1192, 1142, 1078; δH (CDCl3, 300 MHz) 4.03 (1H, dt, J 11.2 and 3.2), 3.70 (1H, t, J 11.2), 3.48 (1H, dd, J 11.2 and 3.2), 3.24 (6H, s), 2.69 (1H, m), 2.17 (1H, d, J 4.2), 2.01 (1H, d, J 7.1), 1.27 (3H, s), 1.25 (3H, s), 1.24 (9H, s); δc (75 MHz, CDCl3) 99.2, 98.2, 65.2, 61.1, 56.8, 48.0, 29.9, 24.9, 22.6, 17.5; m/z (ESI+) 344 (M+23, 100%), 322 (M+1, 4); HRMS calculated for [C14H28NO5S]+ (M+Na+) 322.1683, found 322.1686.
(2S)-1-[S-(1,1-dimethylethyl)sulfonyl]-2-[(2S*,5R*,6R*)-2-(5,6-dimethoxy-5,6- dimethyl-1,4-dioxacyclohexyl)]aziridine
To a solution of(2S)-1-[S-(S*)-(1,1-dimethylethyl)sulfinyl]-2-[(2S*,5R*,6R*)-2-(5,6-dimethoxy -5,6-dimethyl-1,4-dioxacyclohexyl)]aziridine (47 mg, 0.146 mmol) in anhydrous dichloromethane (1.5 ml) was added a 75% solution of m-chloroperoxybenzoic acid in water (34 mg, 0.148 mmol) and the mixture was stirred for five minutes. A saturated aqueous solution of sodium bicarbonate (2 ml) was added and the product was extracted with dichloromethane (2 ml) and washed with brine (2 × 1 ml). The organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to afford the title compound (47 mg, 95% yield). Recrystallization with ethyl ether/petroleum ether afforded the title compound as white crystals. m.p. = 90–95 °C; [α]D -136 (c 1/2, CHCl3); νmax (CHCl3)/cm-1 3011, 1522, 1477, 1424, 1193, 1034; δH (CDCl3, 300 MHz) 3.74–3.60 (2H, m), 3.47 (1H, d, J 9.5), 3.20 (3H, s), 3.18 (3H, s), 2.68 (1H, dd, J 6.9 and 4.4), 2.55 (1H, d, J 6.9), 2.20 (1H, d, J 4.4), 1.41 (9H, s), 1.21 (6H, s); δc (75 MHz, CDCl3) 99.2, 98.2, 67.4, 60.9, 59.6, 48.0, 36.7, 31.8, 24.1, 17.6; m/z (ESI+) 360 (M+23, 100%), 338 (M+1, 7); HRMS calculated for [C14H27NNaO6S]+ (M+Na+) 360.1451, found 360.1460.
All H atoms were placed in calculated positions and allowed to ride during subsequent with Uiso(H) = 1.5Ueq(C) and C—H distances of 0.98 Å for the methyl H atoms, Uiso(H) = 1.2Ueq(C) and C—H distances of 0.99 Å for the methylene H atoms, and Uiso(H) = 1.2Ueq(C) and C—H distances of 1.00 Å for the methine H atoms.
Chiral non-racemic three-carbon building blocks are common intermediates used in the assembly of many HIV protease inhibitors as demonstrated by Honda et al. (2004) and Izawa & Onishi (2006). Working with not epoxide but aziridine functionality offers the synthetic organic chemist a viable alternative approach toward the advancement of these materials of biological and medicinal importance as reported by Chigboh et al. (2008), Ellman et al. (2002), Morton et al. (2006), McGarrigle et al. (2007), and Wakayama & Ellman (2009). As terminal aziridines can be readily obtained using sulfur ylide technologies from the corresponding both enantiomeric lines can be prepared when starting with D-mannitol and ascorbic acid and the properly juxtaposed chiral non-racemic sulfinyl imine. Proof of concept was first published by Forbes et al. (2009). That is, reaction of methylphenylsulfonium methylide with both enantiomeric lines of the butanediacetal-protected chiral non-racemic sulfinyl resulted in dastereomeric ratios of >95:5. The sulfur ylide methylphenylsulfonium methylide was generated in situ upon thermal decarboxylation of carboxylmethyl betaine functionality. Alternatively using trimethylsulfonium iodide in dimethylsulfoxide in the presence of base, the sulfur ylide generated by this route, dimethylsulfonium methylide, reacted as well with the sulfinyl imine [S(S), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide to afford as major isomer the title compound upon oxidation of the sulfinyl aziridine. This was confirmed by NMR analysis of the products obtained using dimethylsulfonium methylide and methylphenylsulfonium methylide with both diastereomeric lines of sulfinyl imine ([S(S), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide and [S(R), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide). Missing is the configuration of the newly formed center of the aziridine upon methylene transfer at C2. While attempts to grow crystals suitable for X-ray analysis of the sulfinyl aziridine itself and derivatives such as the deprotected aziridine were unsuccessful, success was obtained upon oxidation of the sulfinyl aziridine using m-chloroperoxybenzoic acid. The title compound, C14H27NO6S, was isolated in excellent yield and offered definitive evidence of the newly formed aziridine center (C2) as S. The configurations of the preexisting sites C4, C6, and C7 prior to reaction of sulfinyl imine with sulfur ylide are S, R, and R, respectively. The configuration of The C—N bond lengths of the aziridine are 1.478 (2) and 1.486 (2) Å.
For the first synthesis of the title compound, see: Forbes et al. (2009). For the use of sulfinyl in the preparation of aziridines, see: Forbes et al. (2009); Chigboh et al. (2008); Morton et al. (2006). For a review on the use sulfur ylide technologies in the preparation of three-membered rings, see: McGarrigle et al. (2007). For the use of tert-butyl sulfinyl groups as stereodiscriminating groups, see: Ellman et al. (2002); Wakayama & Ellman (2009). For the use of three-carbon building blocks in the assembly of systems of medicinal significance, specifically HIV protease inhibitors, see: Izawa & Onishi (2006); Honda et al. (2004).
Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell CrysAlis PRO (Oxford Diffraction, 2010); data reduction: CrysAlis PRO (Oxford Diffraction, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).
![[Figure 1]](./hb5738fig1thm.gif)
| C14H27NO6S | F(000) = 364 |
| Mr = 337.43 | Dx = 1.265 Mg m−3 |
| Monoclinic, P21 | Cu Kα radiation, λ = 1.5418 Å |
| Hall symbol: P 2yb | Cell parameters from 44949 reflections |
| a = 8.31483 (9) Å | θ = 4.3–73.3° |
| b = 10.31672 (10) Å | µ = 1.86 mm−1 |
| c = 10.33015 (11) Å | T = 90 K |
| β = 91.0961 (10)° | Slab, colourless |
| V = 885.98 (2) Å3 | 0.95 × 0.67 × 0.15 mm |
| Z = 2 |
| Oxford Diffraction SuperNova, single source at offset, Atlas diffractometer | 3548 independent reflections |
| Radiation source: SuperNova (Cu) X-ray Source | 3532 reflections with I > 2σ(I) |
| Mirror monochromator | Rint = 0.082 |
| Detector resolution: 10.3613 pixels mm-1 | θmax = 73.4°, θmin = 4.3° |
| ω scans | h = −10→10 |
| Absorption correction: analytical [CrysAlis PRO (Oxford Diffraction, 2010); analytical numeric absorption correction using a multifaceted crystal model (Clark & Reid, 1995)] | k = −12→12 |
| Tmin = 0.320, Tmax = 0.764 | l = −12→12 |
| 48647 measured reflections |
| Refinement on F2 | Secondary atom site location: difference Fourier map |
| Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
| R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
| wR(F2) = 0.104 | w = 1/[σ2(Fo2) + (0.0774P)2 + 0.1298P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.10 | (Δ/σ)max < 0.001 |
| 3548 reflections | Δρmax = 0.25 e Å−3 |
| 206 parameters | Δρmin = −0.36 e Å−3 |
| 1 restraint | Absolute structure: Flack (1983), 1653 Friedel pairs |
| Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.009 (13) |
| C14H27NO6S | V = 885.98 (2) Å3 |
| Mr = 337.43 | Z = 2 |
| Monoclinic, P21 | Cu Kα radiation |
| a = 8.31483 (9) Å | µ = 1.86 mm−1 |
| b = 10.31672 (10) Å | T = 90 K |
| c = 10.33015 (11) Å | 0.95 × 0.67 × 0.15 mm |
| β = 91.0961 (10)° |
| Oxford Diffraction SuperNova, single source at offset, Atlas diffractometer | 3548 independent reflections |
| Absorption correction: analytical [CrysAlis PRO (Oxford Diffraction, 2010); analytical numeric absorption correction using a multifaceted crystal model (Clark & Reid, 1995)] | 3532 reflections with I > 2σ(I) |
| Tmin = 0.320, Tmax = 0.764 | Rint = 0.082 |
| 48647 measured reflections |
| R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
| wR(F2) = 0.104 | Δρmax = 0.25 e Å−3 |
| S = 1.10 | Δρmin = −0.36 e Å−3 |
| 3548 reflections | Absolute structure: Flack (1983), 1653 Friedel pairs |
| 206 parameters | Absolute structure parameter: −0.009 (13) |
| 1 restraint |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
| x | y | z | Uiso*/Ueq | ||
| N1 | 0.37564 (17) | 0.58231 (13) | 0.58518 (14) | 0.0196 (3) | |
| C2 | 0.5315 (2) | 0.51956 (18) | 0.61615 (16) | 0.0205 (3) | |
| H2 | 0.5588 | 0.4412 | 0.5639 | 0.025* | |
| C3 | 0.5278 (2) | 0.6453 (2) | 0.54586 (19) | 0.0284 (4) | |
| H3A | 0.5631 | 0.7238 | 0.5937 | 0.034* | |
| H3B | 0.5539 | 0.6448 | 0.4528 | 0.034* | |
| C4 | 0.56425 (18) | 0.51094 (17) | 0.75921 (15) | 0.0186 (3) | |
| H4 | 0.5312 | 0.5935 | 0.8019 | 0.022* | |
| O5 | 0.73405 (13) | 0.49225 (12) | 0.77640 (10) | 0.0181 (2) | |
| C6 | 0.7813 (2) | 0.48353 (17) | 0.90943 (15) | 0.0190 (3) | |
| C7 | 0.6875 (2) | 0.37256 (17) | 0.97603 (16) | 0.0199 (3) | |
| O8 | 0.51910 (14) | 0.38873 (12) | 0.95304 (11) | 0.0205 (3) | |
| C9 | 0.4763 (2) | 0.39781 (17) | 0.81885 (16) | 0.0198 (3) | |
| H9A | 0.3587 | 0.4105 | 0.8087 | 0.024* | |
| H9B | 0.5055 | 0.3165 | 0.7741 | 0.024* | |
| O10 | 0.73723 (16) | 0.59700 (13) | 0.97601 (13) | 0.0243 (3) | |
| C11 | 0.8058 (3) | 0.7144 (2) | 0.9290 (2) | 0.0368 (5) | |
| H11B | 0.7977 | 0.7160 | 0.8342 | 0.055* | |
| H11C | 0.9192 | 0.7192 | 0.9562 | 0.055* | |
| H11A | 0.7476 | 0.7887 | 0.9643 | 0.055* | |
| C12 | 0.9618 (2) | 0.46183 (19) | 0.90905 (17) | 0.0238 (4) | |
| H12A | 1.0041 | 0.4623 | 0.9983 | 0.036* | |
| H12C | 1.0131 | 0.5312 | 0.8598 | 0.036* | |
| H12B | 0.9850 | 0.3780 | 0.8689 | 0.036* | |
| O13 | 0.74372 (15) | 0.25843 (12) | 0.91606 (12) | 0.0219 (3) | |
| C14 | 0.6670 (2) | 0.14069 (18) | 0.95495 (18) | 0.0261 (4) | |
| H14C | 0.6912 | 0.0718 | 0.8930 | 0.039* | |
| H14A | 0.5504 | 0.1541 | 0.9572 | 0.039* | |
| H14B | 0.7068 | 0.1157 | 1.0413 | 0.039* | |
| C15 | 0.7090 (2) | 0.3703 (2) | 1.12238 (17) | 0.0293 (4) | |
| H15A | 0.6786 | 0.4547 | 1.1580 | 0.044* | |
| H15C | 0.8219 | 0.3522 | 1.1449 | 0.044* | |
| H15B | 0.6406 | 0.3026 | 1.1587 | 0.044* | |
| S16 | 0.26511 (4) | 0.50297 (4) | 0.47432 (3) | 0.02020 (12) | |
| O17 | 0.21224 (16) | 0.38671 (12) | 0.53743 (14) | 0.0278 (3) | |
| O18 | 0.35073 (16) | 0.48822 (16) | 0.35537 (13) | 0.0323 (3) | |
| C19 | 0.09768 (19) | 0.61192 (18) | 0.45030 (16) | 0.0205 (3) | |
| C20 | 0.1621 (2) | 0.74360 (18) | 0.40680 (19) | 0.0267 (4) | |
| H20A | 0.2301 | 0.7807 | 0.4759 | 0.040* | |
| H20C | 0.0718 | 0.8021 | 0.3880 | 0.040* | |
| H20B | 0.2256 | 0.7323 | 0.3287 | 0.040* | |
| C21 | 0.0075 (2) | 0.62361 (19) | 0.57736 (18) | 0.0264 (4) | |
| H21B | −0.0386 | 0.5393 | 0.5998 | 0.040* | |
| H21C | −0.0790 | 0.6876 | 0.5673 | 0.040* | |
| H21A | 0.0822 | 0.6515 | 0.6464 | 0.040* | |
| C22 | −0.0086 (2) | 0.5508 (2) | 0.3442 (2) | 0.0338 (4) | |
| H22B | 0.0512 | 0.5465 | 0.2634 | 0.051* | |
| H22C | −0.1054 | 0.6037 | 0.3308 | 0.051* | |
| H22A | −0.0395 | 0.4631 | 0.3704 | 0.051* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0192 (7) | 0.0145 (7) | 0.0251 (7) | −0.0006 (5) | 0.0015 (5) | 0.0016 (5) |
| C2 | 0.0174 (7) | 0.0205 (9) | 0.0239 (8) | 0.0015 (6) | 0.0039 (6) | 0.0021 (6) |
| C3 | 0.0226 (8) | 0.0290 (9) | 0.0335 (9) | −0.0073 (7) | 0.0004 (7) | 0.0119 (8) |
| C4 | 0.0168 (7) | 0.0169 (8) | 0.0221 (7) | −0.0004 (7) | 0.0040 (5) | 0.0012 (6) |
| O5 | 0.0171 (5) | 0.0175 (5) | 0.0199 (5) | −0.0001 (5) | 0.0038 (4) | 0.0014 (5) |
| C6 | 0.0200 (7) | 0.0165 (8) | 0.0207 (7) | −0.0008 (6) | 0.0033 (6) | −0.0021 (6) |
| C7 | 0.0217 (9) | 0.0182 (8) | 0.0200 (7) | −0.0015 (7) | 0.0041 (6) | 0.0003 (6) |
| O8 | 0.0210 (6) | 0.0214 (6) | 0.0192 (5) | −0.0015 (5) | 0.0055 (4) | 0.0001 (4) |
| C9 | 0.0194 (8) | 0.0183 (8) | 0.0219 (7) | −0.0021 (6) | 0.0022 (6) | 0.0006 (6) |
| O10 | 0.0259 (6) | 0.0176 (6) | 0.0297 (7) | −0.0045 (5) | 0.0081 (5) | −0.0067 (5) |
| C11 | 0.0378 (12) | 0.0178 (9) | 0.0553 (13) | −0.0092 (8) | 0.0160 (10) | −0.0113 (9) |
| C12 | 0.0195 (8) | 0.0272 (9) | 0.0248 (8) | −0.0014 (6) | 0.0018 (6) | 0.0020 (7) |
| O13 | 0.0252 (6) | 0.0164 (6) | 0.0244 (6) | 0.0008 (5) | 0.0077 (5) | 0.0020 (5) |
| C14 | 0.0285 (9) | 0.0189 (8) | 0.0312 (9) | −0.0007 (7) | 0.0089 (7) | 0.0066 (7) |
| C15 | 0.0326 (9) | 0.0358 (10) | 0.0196 (8) | −0.0043 (8) | 0.0031 (7) | 0.0015 (8) |
| S16 | 0.0213 (2) | 0.0156 (2) | 0.0238 (2) | 0.00156 (15) | 0.00127 (14) | −0.00083 (14) |
| O17 | 0.0297 (7) | 0.0131 (6) | 0.0404 (7) | −0.0024 (5) | −0.0035 (5) | 0.0021 (5) |
| O18 | 0.0329 (7) | 0.0361 (8) | 0.0281 (6) | 0.0092 (6) | 0.0054 (5) | −0.0064 (6) |
| C19 | 0.0188 (8) | 0.0192 (8) | 0.0235 (8) | 0.0012 (6) | 0.0024 (6) | 0.0046 (6) |
| C20 | 0.0278 (9) | 0.0205 (8) | 0.0321 (9) | 0.0031 (7) | 0.0087 (7) | 0.0081 (7) |
| C21 | 0.0237 (8) | 0.0248 (9) | 0.0310 (9) | 0.0049 (7) | 0.0093 (7) | 0.0073 (7) |
| C22 | 0.0289 (9) | 0.0398 (11) | 0.0323 (9) | −0.0014 (8) | −0.0068 (8) | 0.0023 (9) |
| N1—C2 | 1.478 (2) | C12—H12A | 0.9800 |
| N1—C3 | 1.486 (2) | C12—H12C | 0.9800 |
| N1—S16 | 1.6690 (14) | C12—H12B | 0.9800 |
| C2—C3 | 1.487 (3) | O13—C14 | 1.433 (2) |
| C2—C4 | 1.500 (2) | C14—H14C | 0.9800 |
| C2—H2 | 1.0000 | C14—H14A | 0.9800 |
| C3—H3A | 0.9900 | C14—H14B | 0.9800 |
| C3—H3B | 0.9900 | C15—H15A | 0.9800 |
| C4—O5 | 1.4326 (18) | C15—H15C | 0.9800 |
| C4—C9 | 1.515 (2) | C15—H15B | 0.9800 |
| C4—H4 | 1.0000 | S16—O17 | 1.4380 (14) |
| O5—C6 | 1.4248 (18) | S16—O18 | 1.4399 (14) |
| C6—O10 | 1.410 (2) | S16—C19 | 1.8027 (17) |
| C6—C12 | 1.518 (2) | C19—C21 | 1.529 (2) |
| C6—C7 | 1.553 (2) | C19—C22 | 1.531 (3) |
| C7—O13 | 1.414 (2) | C19—C20 | 1.531 (2) |
| C7—O8 | 1.425 (2) | C20—H20A | 0.9800 |
| C7—C15 | 1.519 (2) | C20—H20C | 0.9800 |
| O8—C9 | 1.428 (2) | C20—H20B | 0.9800 |
| C9—H9A | 0.9900 | C21—H21B | 0.9800 |
| C9—H9B | 0.9900 | C21—H21C | 0.9800 |
| O10—C11 | 1.428 (2) | C21—H21A | 0.9800 |
| C11—H11B | 0.9800 | C22—H22B | 0.9800 |
| C11—H11C | 0.9800 | C22—H22C | 0.9800 |
| C11—H11A | 0.9800 | C22—H22A | 0.9800 |
| C2—N1—C3 | 60.21 (11) | C6—C12—H12C | 109.5 |
| C2—N1—S16 | 113.74 (11) | H12A—C12—H12C | 109.5 |
| C3—N1—S16 | 119.18 (12) | C6—C12—H12B | 109.5 |
| N1—C2—C3 | 60.17 (11) | H12A—C12—H12B | 109.5 |
| N1—C2—C4 | 112.41 (14) | H12C—C12—H12B | 109.5 |
| C3—C2—C4 | 122.30 (16) | C7—O13—C14 | 115.48 (12) |
| N1—C2—H2 | 116.4 | O13—C14—H14C | 109.5 |
| C3—C2—H2 | 116.4 | O13—C14—H14A | 109.5 |
| C4—C2—H2 | 116.4 | H14C—C14—H14A | 109.5 |
| N1—C3—C2 | 59.62 (11) | O13—C14—H14B | 109.5 |
| N1—C3—H3A | 117.8 | H14C—C14—H14B | 109.5 |
| C2—C3—H3A | 117.8 | H14A—C14—H14B | 109.5 |
| N1—C3—H3B | 117.8 | C7—C15—H15A | 109.5 |
| C2—C3—H3B | 117.8 | C7—C15—H15C | 109.5 |
| H3A—C3—H3B | 114.9 | H15A—C15—H15C | 109.5 |
| O5—C4—C2 | 106.87 (12) | C7—C15—H15B | 109.5 |
| O5—C4—C9 | 109.16 (13) | H15A—C15—H15B | 109.5 |
| C2—C4—C9 | 111.49 (13) | H15C—C15—H15B | 109.5 |
| O5—C4—H4 | 109.8 | O17—S16—O18 | 117.33 (9) |
| C2—C4—H4 | 109.8 | O17—S16—N1 | 105.49 (7) |
| C9—C4—H4 | 109.8 | O18—S16—N1 | 111.26 (8) |
| C6—O5—C4 | 112.39 (11) | O17—S16—C19 | 109.91 (8) |
| O10—C6—O5 | 110.41 (13) | O18—S16—C19 | 109.97 (8) |
| O10—C6—C12 | 112.95 (14) | N1—S16—C19 | 101.67 (8) |
| O5—C6—C12 | 105.14 (13) | C21—C19—C22 | 111.19 (15) |
| O10—C6—C7 | 104.98 (13) | C21—C19—C20 | 111.23 (15) |
| O5—C6—C7 | 110.01 (13) | C22—C19—C20 | 110.84 (15) |
| C12—C6—C7 | 113.42 (14) | C21—C19—S16 | 108.74 (11) |
| O13—C7—O8 | 110.88 (13) | C22—C19—S16 | 105.99 (14) |
| O13—C7—C15 | 112.93 (15) | C20—C19—S16 | 108.67 (12) |
| O8—C7—C15 | 105.33 (13) | C19—C20—H20A | 109.5 |
| O13—C7—C6 | 104.27 (13) | C19—C20—H20C | 109.5 |
| O8—C7—C6 | 109.87 (14) | H20A—C20—H20C | 109.5 |
| C15—C7—C6 | 113.65 (15) | C19—C20—H20B | 109.5 |
| C7—O8—C9 | 113.28 (12) | H20A—C20—H20B | 109.5 |
| O8—C9—C4 | 109.40 (13) | H20C—C20—H20B | 109.5 |
| O8—C9—H9A | 109.8 | C19—C21—H21B | 109.5 |
| C4—C9—H9A | 109.8 | C19—C21—H21C | 109.5 |
| O8—C9—H9B | 109.8 | H21B—C21—H21C | 109.5 |
| C4—C9—H9B | 109.8 | C19—C21—H21A | 109.5 |
| H9A—C9—H9B | 108.2 | H21B—C21—H21A | 109.5 |
| C6—O10—C11 | 115.42 (13) | H21C—C21—H21A | 109.5 |
| O10—C11—H11B | 109.5 | C19—C22—H22B | 109.5 |
| O10—C11—H11C | 109.5 | C19—C22—H22C | 109.5 |
| H11B—C11—H11C | 109.5 | H22B—C22—H22C | 109.5 |
| O10—C11—H11A | 109.5 | C19—C22—H22A | 109.5 |
| H11B—C11—H11A | 109.5 | H22B—C22—H22A | 109.5 |
| H11C—C11—H11A | 109.5 | H22C—C22—H22A | 109.5 |
| C6—C12—H12A | 109.5 | ||
| S16—N1—C2—C3 | 111.22 (14) | C6—C7—O8—C9 | 55.06 (17) |
| C3—N1—C2—C4 | 115.46 (17) | C7—O8—C9—C4 | −58.42 (18) |
| S16—N1—C2—C4 | −133.32 (13) | O5—C4—C9—O8 | 58.54 (17) |
| S16—N1—C3—C2 | −102.22 (14) | C2—C4—C9—O8 | 176.38 (13) |
| C4—C2—C3—N1 | −99.05 (17) | O5—C6—O10—C11 | −59.72 (19) |
| N1—C2—C4—O5 | −160.31 (14) | C12—C6—O10—C11 | 57.7 (2) |
| C3—C2—C4—O5 | −92.39 (19) | C7—C6—O10—C11 | −178.25 (16) |
| N1—C2—C4—C9 | 80.49 (18) | O8—C7—O13—C14 | −57.86 (17) |
| C3—C2—C4—C9 | 148.40 (16) | C15—C7—O13—C14 | 60.08 (19) |
| C2—C4—O5—C6 | 179.52 (14) | C6—C7—O13—C14 | −176.06 (14) |
| C9—C4—O5—C6 | −59.78 (17) | C2—N1—S16—O17 | 70.35 (13) |
| C4—O5—C6—O10 | −58.81 (16) | C3—N1—S16—O17 | 138.26 (13) |
| C4—O5—C6—C12 | 179.07 (14) | C2—N1—S16—O18 | −57.90 (14) |
| C4—O5—C6—C7 | 56.60 (17) | C3—N1—S16—O18 | 10.01 (16) |
| O10—C6—C7—O13 | −174.97 (12) | C2—N1—S16—C19 | −174.94 (12) |
| O5—C6—C7—O13 | 66.24 (15) | C3—N1—S16—C19 | −107.03 (14) |
| C12—C6—C7—O13 | −51.20 (17) | O17—S16—C19—C21 | 48.33 (14) |
| O10—C6—C7—O8 | 66.15 (16) | O18—S16—C19—C21 | 178.96 (13) |
| O5—C6—C7—O8 | −52.65 (17) | N1—S16—C19—C21 | −63.07 (13) |
| C12—C6—C7—O8 | −170.08 (13) | O17—S16—C19—C22 | −71.29 (14) |
| O10—C6—C7—C15 | −51.58 (18) | O18—S16—C19—C22 | 59.34 (14) |
| O5—C6—C7—C15 | −170.38 (14) | N1—S16—C19—C22 | 177.31 (12) |
| C12—C6—C7—C15 | 72.19 (19) | O17—S16—C19—C20 | 169.54 (12) |
| O13—C7—O8—C9 | −59.68 (17) | O18—S16—C19—C20 | −59.83 (14) |
| C15—C7—O8—C9 | 177.84 (14) | N1—S16—C19—C20 | 58.14 (13) |
Experimental details
| Crystal data | |
| Chemical formula | C14H27NO6S |
| Mr | 337.43 |
| Crystal system, space group | Monoclinic, P21 |
| Temperature (K) | 90 |
| a, b, c (Å) | 8.31483 (9), 10.31672 (10), 10.33015 (11) |
| β (°) | 91.0961 (10) |
| V (Å3) | 885.98 (2) |
| Z | 2 |
| Radiation type | Cu Kα |
| µ (mm−1) | 1.86 |
| Crystal size (mm) | 0.95 × 0.67 × 0.15 |
| Data collection | |
| Diffractometer | Oxford Diffraction SuperNova, single source at offset, Atlas |
| Absorption correction | Analytical [CrysAlis PRO (Oxford Diffraction, 2010); analytical numeric absorption correction using a multifaceted crystal model (Clark & Reid, 1995)] |
| Tmin, Tmax | 0.320, 0.764 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 48647, 3548, 3532 |
| Rint | 0.082 |
| (sin θ/λ)max (Å−1) | 0.622 |
| Refinement | |
| R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.104, 1.10 |
| No. of reflections | 3548 |
| No. of parameters | 206 |
| No. of restraints | 1 |
| H-atom treatment | H-atom parameters constrained |
| Δρmax, Δρmin (e Å−3) | 0.25, −0.36 |
| Absolute structure | Flack (1983), 1653 Friedel pairs |
| Absolute structure parameter | −0.009 (13) |
Computer programs: CrysAlis PRO (Oxford Diffraction, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009), publCIF (Westrip, 2010).
Acknowledgements
This work was supported in part by the NIGMS (NIH NIGMS 1R15GM085936), the NSF (CHE 0957482), and the Camille and Henry Dreyfus Foundation (TH-06–008). The authors are grateful for the assistance and input of Dr Richard Sykora (University of South Alabama).
References
Chigboh, K., Morton, D., Nadin, A. & Stockman, R. A. (2008). Tetrahedron Lett. 49, 4768–4770. Web of Science CrossRef CAS Google Scholar
Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897. CrossRef CAS Web of Science IUCr Journals Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Ellman, J. A., Owens, T. D. & Tang, P. T. (2002). Acc. Chem. Res. 35, 984–995. Web of Science CrossRef PubMed CAS Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Forbes, D. C., Bettigeri, S. V. & Pischek, S. C. (2009). Chem. Commun. pp. 1882–1884. Web of Science CrossRef Google Scholar
Honda, Y., Katayama, S., Kojima, M., Suzuki, T., Kishibata, N. & Izawa, K. (2004). Org. Biomol. Chem. 2, 2061–2070. Web of Science CrossRef PubMed CAS Google Scholar
Izawa, K. & Onishi, T. (2006). Chem. Rev. 106, 2811–2827. Web of Science CrossRef PubMed CAS Google Scholar
McGarrigle, E. M., Myers, E. L., Illa, O., Shaw, M. A., Riches, S. L. & Aggarwal, V. K. (2007). Chem. Rev. 107, 5841–5883. Web of Science CrossRef PubMed CAS Google Scholar
Morton, D. & Stockman, R. A. (2006). Tetrahedron, 62, 8869–8905. Web of Science CrossRef CAS Google Scholar
Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wakayama, M. & Ellman, J. A. (2009). J. Org. Chem. 74, 2646–2650. Web of Science CrossRef PubMed CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
| CRYSTALLOGRAPHIC COMMUNICATIONS |
Chiral non-racemic three-carbon building blocks are common intermediates used in the assembly of many HIV protease inhibitors as demonstrated by Honda et al. (2004) and Izawa & Onishi (2006). Working with not epoxide but aziridine functionality offers the synthetic organic chemist a viable alternative approach toward the advancement of these materials of biological and medicinal importance as reported by Chigboh et al. (2008), Ellman et al. (2002), Morton et al. (2006), McGarrigle et al. (2007), and Wakayama & Ellman (2009). As terminal aziridines can be readily obtained using sulfur ylide technologies from the corresponding imines, both enantiomeric lines can be prepared when starting with D-mannitol and ascorbic acid and the properly juxtaposed chiral non-racemic sulfinyl imine. Proof of concept was first published by Forbes et al. (2009). That is, reaction of methylphenylsulfonium methylide with both enantiomeric lines of the butanediacetal-protected chiral non-racemic sulfinyl imines resulted in dastereomeric ratios of >95:5. The sulfur ylide methylphenylsulfonium methylide was generated in situ upon thermal decarboxylation of carboxylmethyl betaine functionality. Alternatively using trimethylsulfonium iodide in dimethylsulfoxide in the presence of base, the sulfur ylide generated by this route, dimethylsulfonium methylide, reacted as well with the sulfinyl imine [S(S), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide to afford as major isomer the title compound upon oxidation of the sulfinyl aziridine. This was confirmed by NMR analysis of the products obtained using dimethylsulfonium methylide and methylphenylsulfonium methylide with both diastereomeric lines of sulfinyl imine ([S(S), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide and [S(R), N(E)]-2-methyl-N-[((2S,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxacyclohexyl)methylene]-2-propanesulfinamide). Missing is the configuration of the newly formed center of the aziridine upon methylene transfer at C2. While attempts to grow crystals suitable for X-ray analysis of the sulfinyl aziridine itself and derivatives such as the deprotected aziridine were unsuccessful, success was obtained upon oxidation of the sulfinyl aziridine using m-chloroperoxybenzoic acid. The title compound, C14H27NO6S, was isolated in excellent yield and offered definitive evidence of the newly formed aziridine center (C2) as S. The configurations of the preexisting sites C4, C6, and C7 prior to reaction of sulfinyl imine with sulfur ylide are S, R, and R, respectively. The configuration of The C—N bond lengths of the aziridine are 1.478 (2) and 1.486 (2) Å.