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DOI: 10.1055/s-0032-1316759
Development of Tartaric Acid Derived Hydrogen-Bond Donors
Publication History
Received: 24 May 2012
Accepted after revision: 29 June 2012
Publication Date:
03 September 2012 (online)
Abstract
A flexible synthesis of bifunctional thiourea derivatives based on the TADDOL framework is described. Hydroxy as well as primary, secondary, and tertiary amino-substituted bifunctional hydrogen-bond donors were synthesized.
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The α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL, 1, Figure [1, ]R3 = aryl, X = Y = OH) framework is one of the most generally utilized structures in catalysis. Since their introduction as privileged ligands for Lewis acid catalyzed asymmetric transformations a large number of derivatives have been synthesized.[ 1 ] However, lately TADDOL itself has been discovered as a highly selective catalyst in hydrogen-bond-mediated reactions.[ 2 ] In this field of organocatalysis, thiourea derivatives have been widely recognized as efficient catalysts for asymmetric transformations.[ 3 ] Just recently, the use of TADDOL-based urea derivatives as chiral selectors in anion recognition was reported by Gherase.[ 4 ] Despite the great impact of both the TADDOL and the thiourea moieties on organic transformations, the fusion of the two catalytically active elements into one scaffold to provide access to hydrogen-bond catalysts has not been reported yet. Inspired by this concept we approached the synthesis of structurally diverging thiourea derivatives based on the TADDOL-framework (Figure [1]).
This can be easily achieved by straightforward modifications at the quaternary carbon atom (R3 = H, alkyl, aryl) and by the introduction of additional functionalities (Figure [1, ]Y = OH, NH2, NHR, NR2). On this platform, ten new thiourea derivatives were synthesized.
Key requirements for the design of catalysts or ligands are easy access and potential for derivatization. These prerequisites are met by the TADDOL-framework since a number of the corresponding amino alcohols or diamines derived from 1 are described in the literature and can be obtained in one to two steps.[ 5 ] Bifunctional[ 6 ] thiourea derivatives are usually obtained from the reaction of primary or secondary amines bearing a second functional group (e.g., amine, hydroxy, phosphine) with isothiocyanate. These bifunctional starting materials can be varied in the substitution pattern at the carbinol/aminyl carbon atom (Figure [1]). The amino alcohol and diamine derivatives 2 and 3 were prepared according to literature procedures[ 5 ] starting from enantiomerically pure TADDOL [(4R,5R)-1, Scheme [1]].
Treatment of 2 and 3 with 3,5-(trifluoromethyl)phenyl isothiocyanate (4)[ 7 ] in tetrahydrofuran furnished the novel bifunctional thiourea derivatives 5 and 6 in excellent yields (89% and 80%). The 1H NMR resonances at 10.00 ppm for 5 and 12.62 ppm for 6 indicate the s-cis/trans conformation of the thiourea moieties. Both low-field resonances may arise from internal hydrogen bonding of the thiourea NH to the heteroatom. This conjecture is supported by the crystal structure analysis of 5 (Figure [2a]).[ 8 ]
The solid-state structure exhibits the s-cis/trans conformation of the thiourea moiety. The short distance between H1A and O1 (1.838 Å) is characteristic for an internal hydrogen bond, which has also been identified in solution by 1H NMR spectroscopy (vide supra). The thiourea 5 crystallized from ethyl acetate as solvent adduct. The short distance of O1–O65 (2.779 Å, 3.04 Å sum of van der Waals radii)[ 11 ] specifies an intermolecular hydrogen bond to the ethyl acetate molecule. Since the intramolecular hydrogen bond might have a significant impact on the catalysts’ activity the corresponding more flexible methylenehydroxy 7 and amino compounds 8 were synthesized (Scheme [2]).
The amino alcohol 9 and the diamine 10 were obtained in two steps from the 1,3-dioxolane diester 11 in 87% and 65% yield, respectively.[ 12 ] The amino compounds were treated with isothiocyanate 4 to form the corresponding thiourea derivatives 7 and 8 (89% and 50% yield). In contrast to the TADDOL-derived thiourea compounds 5 and 6 (Scheme [1]) the methylene compounds 7 and 8 (Scheme [2]) revealed enhanced conformational flexibility as concluded from the 1H NMR spectra. Only one NH resonance of the thiourea moiety was observed (7: 10.19 ppm and 8: 6.2–4.8 ppm, broad signal) displaying conformational interchange on NMR timescale. The primary amines 6 and 8 were further converted to secondary or tertiary amines, imines, amides, or heterocycles. This offers a versatile handle for catalyst derivatization and ultimately for structure optimization. Two methodologies for the derivatization of 6 and 8 were investigated: the reductive amination with aldehydes and the condensation with 1,4-diketones to pyrroles. Surprisingly the direct reductive amination of aminothiourea 6 with aldehydes was unsuccessful (data not shown).[ 13 ] However, we overcame this problem initially by condensing the diamine 3 with benzaldehyde (12) in the presence of p-toluenesulfonic acid resulting in the formation of imine 14 in 71% yield (Scheme [3]).
Subsequent reaction with 4 furnished the previously inaccessible imine 13 in excellent yield (86%). This imine was reduced in 69% yield to the secondary N-benzylamino thiourea 15. As evident from the crystal structure analysis, 15 adopts almost the same conformation as 5 (Figure [2b]) and features an intramolecular hydrogen bond between N8 and H3 (1.956 Å).
As expected from the reduced steric bulk in the α,α′-tetrahydro-1,3-dioxolane diamine framework 10 (Scheme [2]), the reductive amination of 8 was readily achieved in the presence of the thiourea moiety (Scheme [4]).
The reductive amination of 8 with benzaldehyde (12) in the presence of sodium triacetoxyborohydride furnished the secondary amino thiourea derivative 17 under mild reaction conditions in excellent yield (80%). The synthesis of the tertiary amines required harsh reaction conditions. Here, 8 was treated with 16 or 12 and zinc dust in acetic acid. The dimethylamino and the dibenzylamino substituted thiourea derivatives 18 and 19 were isolated in 55% and 85% yield, respectively. Primary amino groups can be transformed to pyrrole derivatives by condensation with 1,4-diketones according to the Paal–Knorr protocol. We used this strategy to shield one half-space of the thiourea moiety.[13b] [14] The condensation of 8 with diketone 20 furnished the pyrrole derivative 21 in excellent yield (Scheme [5]).
As C 2-symmetric bis-thiourea derivatives[ 15 ] have been successfully utilized as organocatalysts in the asymmetric Morita–Baylis–Hillman[ 16 ] (MBH) reaction we synthesized the corresponding tartaric acid derived bis-thiourea 22. The diamine 10 was reacted with two equivalents of 4 furnishing the bis-thiourea 22 in excellent yield (95%, Scheme [6]).
a Yield was determined by gas chromatography with dodecane as internal standard.
b Enantiomeric excess (ee) was determined by HPLC with chiral stationary phase.
To evaluate the potential of the novel thiourea derivatives for asymmetric hydrogen-bond catalysis, the bifunctional structures were subjected to the Friedel–Crafts alkylation of indole. This reaction can be catalyzed by hydrogen-bond donors bearing hydroxy as well as amino functionalities.[ 17 ] The TADDOL-derived hydrogen-bond catalysts 5 and 6 (Table [1]) did not promote the Friedel–Crafts reaction at room temperature, but furnished the product 31 in good yields at slightly elevated temperature (50 °C, Table [1], entries 3 and 4). Other synthesized thiourea derivatives provided the product either in low yield or required higher temperatures. The most efficient catalysts were the tertiary amino-substituted thiourea derivatives 19 and 18 (entries 10 and 11). The product was obtained in 15–43% yield with an enantiomeric excess of 18–27%. In general, the tetraaryl-substituted thiourea derivatives were less efficient in the catalytic reaction and required elevated temperatures. This is in accordance with the observation of the internal hydrogen bonding preventing efficient substrate activation.
In summary, we have developed an efficient access to tartaric acid derived thiourea structures. The flexible synthesis of bifunctional structures bearing hydroxy, amino, and heteroaromatic substituents were demonstrated, which give entry to diverse catalyst structures. The novel bifunctional hydrogen-bond donors were studied in the asymmetric Friedel–Crafts reaction. The tetrahydro-substituted derivatives were active at room temperature but provided the alkylation product with low enantioselectivity. However, the bisalkylated catalyst 18 displayed potential for asymmetric tranformations, and thus straightforward derivatization at the amino group will be the focus of future studies.
1H NMR spectra were recorded on a 400 MHz spectrometer. Chemical shifts are reported in ppm with CHCl3 or DMSO as an internal standard (CHCl3: 7.26 ppm; DMSO: 2.50 ppm). Data are reported as follows: chemical shift, multiplicity (standard abbreviations), coupling constants (Hz), and integration. 13C NMR spectra were recorded on a 100 MHz NMR spectrometer. Chemical shifts are reported in ppm with CHCl3 or DMSO as an internal standard (CHCl3: 77.0 ppm; DMSO: 39.43 ppm). MS: The molecular fragments are quoted as the relation between mass and charge (m/z), and the intensities are percentage value relative to the intensity of the base signal (100%). The abbreviation [M]+ refers to the molecule ion. IR spectra were recorded as KBr pellets or as neat solids (platinum ATR and DRIFT). The deposit of the absorption band was given in wavenumbers (cm–1). Unless otherwise specified, all starting materials, reagents and solvents are commercially available and were used without further purification. Flash column chromatography was carried out on silica gel. Routine monitoring of reactions were performed using silica gel coated aluminum plates (silica gel 60, F254). All reactions involving moisture-sensitive reactants were executed under an argon atmosphere using oven-dried glassware.
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(4R,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-6,6-diphenylmethyl-7,7-diphenylmethanol-1,3-dioxolane)thiourea [(4R,5S)-5]
To a solution of compound 2 (0.92 g, 1.97 mmol, 1.00 equiv) in THF (10 mL) was added compound 4 (0.69 g, 2.56 mmol, 1.30 equiv) and the solution was stirred for 12 h. The volatiles were removed under reduced pressure and the crude product was purified by flash chromatography (cyclohexane–EtOAc, 15:1). The product was obtained as a colorless solid in 89% yield (1.76 mmol, 1.29 g); mp 125 °C (capillary); Rf = 0.42 (cyclohexane–EtOAc, 15:1); [α]D 20 –0.263 (c = 0.5, toluene).
IR: 3347 (w), 3216 (w), 3028 (w), 2927 (w), 2851 (vw), 1560 (w), 1494 (w), 1448 (w), 1371 (w), 1278 (m), 1175 (m), 1137 (m), 886 (w), 705 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ = 0.56 (s, 3 H, CH3), 1.20 (s, 3 H, CH3), 3.24 (s, 1 H, OH), 4.13 (d, J = 7.7 Hz, 1 H, CH), 4.65 (d, J = 7.7 Hz, 1 H, CH), 6.92 (s, 1 H, NH), 7.17–7.24 (m, 6 Harom), 7.28–7.48 (m, 11 Harom), 7.50–7.58 (m, 4 Harom), 7.69–7.77 (m, 2 Harom), 10.00 (s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 26.6 (Cp), 27.0 (Ct), 27.4 (Cp), 68.8 (Cq), 77.3 (Cp), 78.8 (Cq), 80.6 (Ct), 84.6 (Ct), 109.6 (Cq), 118.6 (Ct), 118.9 (Cp), 121.5 (Cq, q, J = 273 Hz), 123.92 (Ct), 127.5 (Ct), 127.5 (Ct), 127.8 (Ct), 128.2 (Ct), 128.5 (Ct), 128.8 (Ct), 128.9 (Ct), 129.3 (Ct), 129.6 (Ct), 129.7 (Ct), 131.5 (Cq, q, J = 34 Hz), 135.4 (Cq), 139.8 (Cq), 141.0 (Cq), 141.3 (Cq), 145.8 (Cq), 180.5 (Cq).
19F NMR (400 MHz, CDCl3): δ = –63.01 (s, 2 × CF3).
MS (FAB, 3-NBA): m/z (%) = 737 (32, [M + H]+), 736 (22, [M]+), 719 (12, [M – OH] +), 704 (12, [M – SH]+), 702 (22, [M – H2S]+), 553 (5, [M – C13H11O·]+), 267 (28), 237 (72), 179 (100), 167 (82), 105 (38).
HRMS: m/z calcd for C40H34F6N2O3S: 737.2228; found: 737.2269.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-6,6-diphenylmethyl-7,7-diphenylmethylamine-1,3-dioxolane)thiourea [(4S,5S)-6]
To a solution of (4S,5S)-3 (1.07 g, 2.30 mmol, 1.00 equiv) in THF (10 mL) was added compound 4 (0.65 g, 2.30 mmol, 1.00 equiv) and the solution was stirred for 12 h. The volatiles were removed under reduced pressure and the crude product was purified by flash chromatography (cyclohexane–EtOAc, 15:1). The product was obtained as a colorless solid in 80% yield (1.84 mmol, 1.35 g); mp 155 °C; Rf = 0.42 (cyclohexane–EtOAc, 15:1); [α]D 20 –0.358 (c = 0.5, toluene).
IR: 3340 (m), 3057 (w), 2985 (w), 2915 (w), 1573 (m), 1513 (w), 1492 (w), 1472 (w), 1448 (w), 1382 (m), 1279 (m), 922 (m), 736 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ = 0.57 (s, 3 H, CH3), 1.22 (s, 3 H, CH3), 2.32 (s, 2 H, NH2), 3.80 (d, J = 8.0 Hz, 1 H, CH), 4.39 (d, J = 8.0 Hz, 1 H, CH), 6.70 (s, 1 H, NH), 7.03–7.21 (m, 6 Harom), 7.28–7.52 (m, 13 Harom), 7.53–7.60 (m, 2 Harom), 7.70–7.77 (m, 2 Harom), 12.62 (s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 26.4 (Cp), 27.3 (Cp), 62.5 (Cq), 68.1 (Cq), 80.3 (Ct), 84.9 (Ct), 108.4 (Cq), 118.4 (Ct), 123.0 (Cq, q, J = 273 Hz), 124.0 (Ct), 126.9 (Ct), 127.0 (Ct), 127.6 (Ct), 127.8 (Ct), 128.2 (Ct), 128.4 (Ct), 128.6 (Ct), 128.8 (Ct), 128.9 (Ct), 129.4 (Ct), 129.6 (Ct), 129.9 (Ct), 131.2 (Cq, q, J = 34 Hz), 135.7 (Cq), 139.8 (Cq), 144.1 (Cq), 141.2 (Cq), 149.9 (Cq), 180.0 (Cq).
19F NMR (400 MHz, CDCl3): δ = –62.87 (s, 2 × CF3).
MS (FAB, 3-NBA): m/z (%) = 736 (15, [M]+), 719 [M – NH2]+, 702 (28, [M – H2S]+), 523 (15, [M – C13H12N· – 2 × ·CH3]+), 237 (47), 179 (100), 167 (50).
HRMS: m/z calcd for C40H35F6N3O2S: 736.2388; found: 737.2435.
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(2S,3S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-4-methyl-5-methanol-1,3-dioxolane)thiourea [(2S,3S)-7]
To a solution of (2S,3S)-9 (600 mg, 3.72 mmol, 1.00 equiv) in CH2Cl2 (40 mL) was added compound 4 (1.01 g, 3.72 mmol, 1.00 equiv) and the reaction mixture was stirred for 24 h at r.t. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography (cyclohexane–EtOAc, 1:1). The product was obtained as a colorless solid in 60% yield (2.25 mmol, 0.97 g); mp 46 °C (capillary); Rf = 0.27 (cyclohexane–EtOAc, 1:1); [α]D 20 +2.72 (c = 1.2, CHCl3).
IR: 3298, 1536, 1471, 1376, 1274, 1167, 1125, 883, 845, 680 cm–1.
1H NMR (400 MHz, DMSO-d 6): δ = 1.33 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 3.54 (t, J = 5.1 Hz, 2 H, CH 2OH), 3.64 (m, 1 H, 1 × CH2), 3.79 (m, 1 H, CH), 3.86 (m, 1 H, 1 × CH2), 4.02 (m, 1 H, CH), 4.91 (br s, 1 H, OH), 7.75 (s, 1 H, Harom), 8.27 (s, 2 H, Harom), 10.19 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d 6): δ = 26.9 (Cp), 27.1 (Cp), 46.2 (Cs), 61.3 (Cs), 76.0 (Ct), 79.1 (Ct), 108.4 (Cq), 116.1 (Ct), 121.8 (Ct), 123.1 (Cq, q, J = 272.7 Hz), 130.1 (Cq, q, J = 32.7 Hz), 141.7 (Cq), 180.7 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = – 61.5 (s, 2 × CF3).
MS (EI): m/z (%) = 432.0 (5, [M+]), 414 (40, [M – OH]+), 356 (20, [C12H10F6N2OS]+), 271 (100, [C9H3F6NS]+), 213 (30, [C8H3F6]+).
HRMS: m/z calcd for C16H18F6N2O3S: 432.0942; found: 432.0940.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-4-methyl-5-methylamine-1,3-dioxolane)thiourea [(4S,5S)-8]
To a solution of (4S,5S)-10 (900 mg, 5.61 mmol, 1.00 equiv) in CH2Cl2 (40 mL) was added compound 4 (1.60 g, 5.61 mmol, 1.00 equiv) and the reaction mixture was stirred for 24 h at r.t. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography (cyclohexane–EtOAc, 1:1). The product was obtained as a colorless solid in 50% yield (2.80 mmol, 1.97 g); mp 61 °C (capillary); Rf = 0.08 (cyclohexane–EtOAc, 1:1); [α]D 20 –5.4 (c = 2.44, CHCl3).
IR: 3269, 2991, 2934, 1703, 1623, 1535, 1471, 1380, 1278, 1136, 887, 682 cm–1.
1H NMR (400 MHz, DMSO-d 6): δ = 1.33 (s, 3 H, CH3), 1.35 (s, 3 H, CH3), 2.75 (m, 2 H, CH2), 3.73 (m, 3 H, CH2, CH), 5.56 (br s, 4 H, NH2), 7.73 (s, 1 Harom), 8.26 (s, 1 Harom).
13C NMR (75 MHz, CDCl3): δ = 26.8 (Cp), 26.9 (Cp), 43.3 (Cs), 60.3 (Cs), 77.0 (Ct), 79.8 (Ct), 108.1 (Cq), 116.1 (Ct), 121.9 (Ct), 123.2 (Cq, q, J = 272.8 Hz), 130.0 (Cq, q, J = 33.4 Hz), 180.7 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –61.59 (s, 2 × CF3).
MS (EI): m/z (%) = 432 (5, [M+ + H]), 414 (55, [M+ + H – NH3]), 356 (35, [M – C3H6O2]+), 271 (100, [C9H4F6NS]+), 229 (52, [C8H4F6N]+), 213 (49, [C8H4F6 +]), 114 (28, [C6H10O2]+), 43 (90, [C3H6O2]+).
HRMS: m/z calcd for C25H22F12N4O2S2: 702.0993; found: 702.09925.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-6,6-diphenylmethyl-7,7-diphenylbenzylmethanamine-1,3-dioxolane)thiourea [(4S,5S)-15]
NaBH(OAc)3 (1.03 mg, 4.80 mmol, 5 equiv) was added to a solution of (4S,5S)-13 (800 mg, 0.97 mmol, 1 equiv) in EtOH (20 mL). The resulting mixture was stirred for 7 days. Then, aq ammonia solution (50 mL) was added and the aqueous phase extracted with CH2Cl2 (2 × 50 mL). The combined organic layers were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (cyclohexane–EtOAc, 20:1). The product was obtained as a colorless solid in 80% yield (0.78 mmol, 0.64 g); mp 178 °C (capillary); Rf = 0.77 (cyclohexane–EtOAc, 1:1); [α]D 20 + 1.67 (c = 0.31, CHCl3).
IR: 3336 (m), 3061 (w), 2931 (m), 1571 (m), 1495 (m), 1471 (m), 1448 (m), 1382 (m), 1278 (s), 1256 (m), 1176 (m), 1136 (s), 1087 (s), 1032 (m), 885 (m), 703 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ = 0.77 (s, 3 H, CH3), 1.33 (s, 3 H, CH3), 1.60 (br s, 1 H, NH), 3.51 (dd, J 3 = 3.8 Hz, J 2 = 12.1 Hz, 1 H, 1 × CH2), 3.65 (dd, J 3 = 4.7 Hz, J 2 = 12.1 Hz, 1 H, 1 × CH2), 4.11 (d, J 3 = 8.2 Hz, 1 H, CH), 4.27 (d, J 3 = 8.2 Hz, 1 H, CH), 6.73 (s, 1 H, NH), 6.86 (m, 2 Harom), 7.16 (m, 8 Harom), 7.42 (m, 16 Harom), 7.87 (m, 2 Harom), 12.47 (s, 1 Harom).
13C NMR (100 MHz, CDCl3): δ = 26.5 (Cp), 26.9 (Cp), 46.7 (Cs), 67.9 (Cq), 68.4 (Cq), 77.3 (Ct), 78.9 (Ct), 85.5 (Ct), 107.7 (Cq), 118.2 (Ct), 121.7 (Cq), 123.5 (Ct), 124.4 (Cq), 127.1 (Ct), 127.5 (Ct), 127.7 (Ct), 127.9 (Ct), 128.0 (Ct), 128.3 (Ct), 128.5 (Ct), 128.6 (Ct), 128.9 (Ct), 129.3 (Ct), 129.5 (Ct), 129.7 (Ct), 131.1 (Cq, q, J = 33.4 Hz), 135.8 (Cq), 139.2 (Cq), 139.9 (Cq), 140.7 (Cq), 141.2 (Cq), 144.2 (Cq), 179.7 (Cq).
19F NMR (376 MHz, CDCl3): δ = –62.9 (s, 2 × CF3).
MS (EI): m/z (%) = 825 (5, [M+]), 791 (10, [C47H39F6N3O2]+), 719 (5, [C40H33F6N2O2]+), 718 (5, [C41H36F6N3O2]+), 554 (5, [C27H23F6N2O2S]+), 370 (5, [C25H23NO2]+), 271 (100, [C9H4F6NS]+), 213 (20, [C8H3F6]+).
HRMS: m/z calcd for C47H39F6N3O2S: 825.2820; found: 825.2823.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-[2,2-dimethyl-4-methyl-5-N-(benzyl)methylamine-1,3-dioxolane]thiourea [(4S,5S)-17]
NaBH(OAc)3 (680 mg, 3.15 mmol, 2.00 equiv) and benzaldehyde (12; 250 mg, 2.36 mmol, 1.5 equiv) were added to a solution of (4S,5S)-8 (680 mg, 1.57 mmol, 1 equiv) in CH2Cl2 (10 mL). The resulting mixture was stirred for 96 h. Then, aq ammonia solution (500 mL) was added and the aqueous phase extracted with CH2Cl2 (2 × 50 mL). The combined organic layers were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (cyclohexane–EtOAc, 7:1). The product was obtained as a colorless solid in 80% yield (1.26 mmol, 0.65 g); mp 56 °C (capillary); Rf = 0.12 (cyclohexane–EtOAc, 7:1); [α]D 20 – 6.05 (c = 1.52, CHCl3).
IR: 2931, 1532, 1470, 1378, 1274, 1167, 1125, 1073, 949, 883, 846, 733, 698, 680, 592 cm–1.
1H NMR (400 MHz, DMSO-d 6): δ = 1.32 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 2.71 (m, 2 H, CH2), 3.65 (dd, J 3 = 6.9 Hz, J 2 = 13.8 Hz, 1 H, 1 × CH2), 3.74 (s, 2 H, CH2), 3.88 (m, 2 H, 1 × CH2, 1 × CH), 4.03 (m, 1 H, CH), 7.03 (br s, 1 H, NH), 7.19 (m, 1 Harom), 7.29 (m, 4 Harom), 7.75 (s, 1 Harom), 8.25 (s, 2 Harom), 10.2 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d 6): δ = 27.0 (Cp), 27.1 (Cp), 46.1 (Cs), 50.3 (Cs), 52.9 (Cs), 77.4 (Ct) 77.8 (Ct), 108.2 (Cq), 116.1 (Ct), 119.2 (Cq), 121.8 (Ct), 124.5 (Ct) 126.5 (Cq), 127.8 (Ct), 128.0 (Ct), 130.1 (Cq, q, J = 33.4 Hz), 141.7 (Cq), 180.7 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –61.54 (s, 2 × CF3).
MS (EI): m/z (%) = 522 (20, [M + H+]), 521 (60, [M]+), 430 (5, [C16H18F6N3O2S]+), 415 (10, [C16H17F6N2O2S]+), 271 (100, [C9H4F6NS]+), 213 (15, [C8H3F6]+), 162 (38, [C10H12NO]+), 120 (80, [C8H10N]+), 91 (100, [C7H7]+), 43 (5, [C3H6O2]+).
HRMS: m/z calcd for C23H25F6N3O2S: 521.1568; found: 521.1571.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-[2,2-dimethyl-4-methyl-5-N-bis(benzyl)methylamine-1,3-dioxolane]thiourea [(4S,5S)-18]
Zn powder (648 mg, 9.92 mmol, 4.00 equiv), AcOH (1.13 mL, 19.84 mmol, 8 equiv), and 37% aq formaldehyde (223 mg, 7.44 mmol, 3 equiv) were added to a solution of (4S,5S)-8 (1.07 g, 2.48 mmol, 1 equiv) in 1,4-dioxane (5 mL). The resulting mixture was stirred for 96 h. Then, aq ammonia solution (500 mL) was added and the aqueous phase extracted with CH2Cl2 (2 × 50 mL). The combined organic layers were dried (MgSO4) and the solvents removed under reduced pressure. The crude product was purified by flash chromatography (CHCl3–MeOH, 1:1). The product was obtained as a colorless solid in 55% yield (1.36 mmol, 0.63 g); mp 54 °C (capillary); Rf = 0.1 (CHCl3–MeOH, 95:5); [α]D 20 –14.38 (c = 1.39, CHCl3).
IR: 2986 (vw), 1535 (w), 1468 (w), 1378 (m), 1274 (m), 1168 (m), 1124 (m), 1168 (m), 1124 (m), 1075 (m), 983 (w), 883 (w), 844 (w), 725 (w), 700 (w), 680 cm–1 (w).
1H NMR (400 MHz, DMSO-d 6): δ = 1.32 (s, 3 H, CH3), 1.35 (s, 3 H, CH3), 2.17 (s, 6 H, 2 × CH3), 2.36 (m, 1 H, CH2), 3.32 (m, 1 H, CH2), 3.65 (m, 1 H, 1 × CH2), 3.87 (m, 2 H, 2 × CH), 3.93 (m, 1 H, 1 × CH2), 7.71 (s, 1 Harom), 8.26 (s, 2 Harom).
13C NMR (100 MHz, DMSO-d 6): δ = 26.7 (Cp), 26.8 (Cp), 45.5 (Cs), 45.6 (Cp), 61.0 (Cs), 76.8 (Ct), 77.8 (Ct), 79.1 (Cq), 108.2 (Cq), 115.5 (Ct), 121.9 (Ct), 129.9 (Cq), 143.0 (Cq), 180.7 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –56.7.
MS (EI): m/z (%) = 459 (10, [M]+), 444 (10, [C17H20F6N3O2S]+), 415 (15, [C16H17F6N2O2S]+), 401 (5, [C15H15F6N2O2S]+), 343 (10, [C12H9F6N2OS]+), 313 (5, [C11H8F6N2S]+), 271 (10, [C9H4F6NS]+), 58 (100, [C3H8N]+).
HRMS: m/z calcd for C18H23F6N3O2S: 459.1414; found: 459.1415.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-[2,2-dimethyl-4-methyl-5-N-bis(benzyl)methylamine-1,3-dioxolane]thiourea [(4S,5S)-19]
Zn powder (648 mg, 9.92 mmol, 4 equiv), AcOH (1.13 mL, 19.84 mmol, 8 equiv), and benzaldehyde (12; 789 mg, 7.44 mmol, 3 equiv) were added to a solution of (4S,5S)-8 (1.07 g, 2.48 mmol, 1 equiv) in 1,4-dioxane (5 mL). The resulting mixture was stirred for 96 h. Then, aq ammonia solution (500 mL) was added and the aqueous phase extracted with CH2Cl2 (2 × 50 mL). The combined organic layers were dried (MgSO4) and the solvents removed under reduced pressure. The crude product was purified by flash chromatography (cyclohexane–EtOAc, 6:1). The product was obtained as a colorless solid in 85% yield (2.11 mmol, 1.29 g); mp 75 °C (capillary); Rf = 0.2 (cyclohexane–EtOAc, 6:1); [α]D 20 –14.38 (c = 1.39, CHCl3).
IR: 2987, 1528, 1453, 1376, 1274, 1169, 1127, 1067, 883, 846, 697, 680, 508 cm–1.
1H NMR (400 MHz, DMSO-d 6): δ = 1.22 (s, 3 H, CH3), 1.34 (s, 3 H, CH3), 2.63 (m, 2 H, CH2), 3.53 (m, 3 H, 1 × CH2, CH2), 3.69 (d, J = 13.7 Hz, 2 H, CH2), 3.80 (m, 1 H, CH), 3.93 (m, 1 H, 1 × CH2), 4.03 (m, 1 H, CH), 7.22 (m, 2 Harom), 7.31 (m, 4 Harom), 7.39 (m, 4 Harom), 7.75 (s, 1 Harom), 8.22 (br s, 1 H, 1 × NH2), 8.28 (s, 1 Harom), 10.23 (br s, 1 H, 1 × NH2).
13C NMR (100 MHz, DMSO-d 6): δ = 26.9 (Cp), 27.0 (Cp), 46.0 (Cs), 55.0 (Cs), 58.1 (Cs), 76.2 (Ct) 77.7 (Ct), 108.4 (Cq), 116.1 (Ct), 121.8 (Ct), 124.5 (Cq) 126.8 (Ct), 128.1 (Ct), 128.6 (Ct), 129.9 (Cq), 139.0 (Cq), 141.7 (Cq), 180.7 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –61.5 (s, 2 × CF3).
MS (EI): m/z (%) = 612 (10, [M + H]+), 611 (20, [M]+), 520 (10, [C23H24F6N3O2S]+), 271 (100, [C9H4F6NS]+), 249 (73, [C18H19N]+), 210 (100, [C15H16N]+), 91 (40, [C7H7]+), 43 (15, [C3H6O2]+).
HRMS: m/z calcd for C30H31F6N3O2S: 611.2043; found: 611.2041.
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(4S,5S)-N-3,5-Bis(trifluoromethyl)phenyl-N′-(2,2-dimethyl-4-methyl-2,4-dimethylpyrrole-1,3-dioxolane)thiourea [(4S,5S)-21]
To a solution of (4S,5S)-8 (300 mg, 0.69 mmol, 1.00 equiv) in EtOH (10 mL) were added 21 (80 mg, 0.69 mmol, 1 equiv) and AcOH (42 mg, 0.69 mmol, 1 equiv) and the reaction mixture was stirred for 24 h. The volatiles were removed under reduced pressure and the crude product was purified by flash chromatography. The product was obtained as a colorless solid in 95% yield (0.66 mmol, 0.33 g); mp 125 °C (capillary); Rf = 0.77 (cyclohexane–EtOAc, 1:1); [α]D 20 +1.55 (c = 0.51, CHCl3).
IR: 3306 (m), 2988 (m), 2936 (m), 1623 (m), 1531 (m), 1472 (m), 1278 (m), 1176 (m), 1135 (m), 885 (w), 847 (w), 758 cm–1 (w).
1H NMR (400 MHz, DMSO-d 6): δ = 1.35 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 2.17 (s, 6 H, 2 × CH3), 3.75 (m, 1 H, CH2), 3.95 (m, 4 H, 1 × CH, 3 × CH2), 4.08 (m, 1 H, 1 × CH), 5.59 (s, 2 H, Harom), 7.76 (s, 1 H, Harom), 8.26 (s, 2 H, Harom), 8.34 (br s, 1 H, NH), 10.21 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d 6): δ = 12.6 (Cp), 26.7 (Cp), 26.9 (Cp), 45.4 (Cs), 45.6 (Cs), 76.5 (Ct) 78.3 (Ct), 105.1 (Ct), 109.1 (Cq), 116.3 (Ct), 122.0 (Ct), 123.6 (Cq, q, J = 272.8 Hz), 127.1 (Cq), 130.0 (Cq, q, J = 32.2 Hz), 141.7 (Cq), 180.9 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –61.5 (s, 2 × CF3).
MS (EI): m/z (%) = 509 (25, [M]+), 475 (10, [M – H2S]+), 271 (15, [C9H4F6NS]+), 222 (15, [C13H20NO2]+), 108 (20, [C7H10N]+), 94 (10, [C6H8N]+), 43 (100, [C3H6O2]+).
HRMS: m/z calcd for C22H25F6N3O2S: 509.1569; found: 509.1571.
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(4S,5S)-4,5-Bis(trifluoromethyl)phenylthiourea)-2,2-dimethyl-1,3-dioxolane [(4S,5S)-22]
To a solution of (2S,3S)-10 (900 mg, 5.61 mmol, 1.00 equiv) in CH2Cl2 (40 mL) was added compound 4 (3.05 g, 11.23 mmol, 2.00 equiv). The reaction mixture was stirred for 24 h at r.t. Then, the solvent was removed under reduced pressure and the crude product was purified by flash chromatography (cyclohexane–EtOAc, 1:1). The product was obtained as a colorless solid in 90% yield (5.06 mmol, 3.55 g); mp 112 °C (capillary); Rf = 0.64 (cyclohexane–EtOAc, 1:1); [α]D 20 +2.3 (c = 1.0, MeOH).
IR: 3269, 2991, 2934, 1703, 1623, 1535, 1471, 1380, 1278, 1136, 887, 682 cm–1.
1H NMR (400 MHz, DMSO-d 6): δ = 1.39 (br s, 6 H, 2 × CH3), 3.71 (br d, J = 12.6 Hz, 2 H, CH2), 3.92 (br d, J = 12.2 Hz, 2 H, CH2), 4.11 (br s, 2 H, 2 × CH), 7.72 (br s, 2 H, 2 × NH), 8.28 (m, 6 Harom), 10.19 (br s, 2 H, 2 × NH).
13C NMR (100 MHz, DMSO-d 6): δ = 27.0 (Cp), 45.7 (Cs), 76.4 (Ct), 108.8 (Cq), 116.2 (Ct), 122.0 (Ct), 123.1 (Cq, q, J = 272.7 Hz), 130.0 (Cq, q, J = 32.3 Hz), 141.7 (Cq), 180.9 (Cq).
19F NMR (376 MHz, DMSO-d 6): δ = –61.6 (s, 2 × CF3).
MS (EI): m/z (%) = 702 (4, [M]+), 414 (50, [M – C9H5F6N2S ]+), 271 (100, [C9H4F6NS]+), 114 (28, [C6H10O2]+).
HRMS: m/z calcd for C25H22F12N4O2S2: 702.0993; found: 702.09925.
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Friedel–Crafts Alkylation of Indole (23) with trans-β-Nitrostyrene (24); General Procedure
To a solution of trans-β-nitrostyrene (24; 7.5 mg, 0.05 mmol) and catalyst (see Table [1]; 0.01 mmol, 20 mol%) in CH2Cl2 (50 μL) was added indole (23; 8.8 mg, 75 μmol). The reaction mixture was stirred for the indicated time at the respective temperature (see Table [1]). The mixture was diluted with Et2O (10 mL) and was subjected to flash chromatography. The yield of product 25 was determined by GC analysis with dodecane (11.4 μL, 0.05 mmol) as internal standard. The enantiomeric excess was determined by HPLC analysis. GC (Zebron ZB-5MS) 80 to 280 °C, ramp: 8 °C/min, t R (dodecane) = 10.0 min, t R (product) = 22.5 min; HPLC (Chiralcel-OD) heptane–i-PrOH (70:30); flow rate: 0.75 mL/min, 0.5 μL, 25 °C.
1H NMR (400 MHz, CDCl3): δ = 4.96 (dd, J = 12.4, 7.2 Hz, 1 H, CH2), 5.07 (dd, J = 12.4, 7.2 Hz, 1 H, CH2), 5.19 (t, J = 8.2 Hz, 1 H, CH), 8.08 (br s, 1 H, NH).
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Acknowledgment
We acknowledge the Fond der Chemischen Industrie for a Liebig grant to J. Paradies. This work was also supported by a grant to M. B. Lauber from the Landesgraduiertenförderung of the State of Baden-Württemberg. We thank Prof. Stefan Bräse for his kind support.
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References
- 1a Seebach D, Beck AK, Heckel A. Angew. Chem. Int. Ed. 2001; 40: 92
- 1b Hintermann L, Togni A. Angew. Chem. Int. Ed. 2000; 39: 4359
- 1c Seebach D, Pichota A, Beck AK, Pinkerton AB, Litz T, Karjalainen J, Gramlich V. Org. Lett. 1999; 1: 55
- 1d Jaeschke G, Seebach D. J. Org. Chem. 1998; 63: 1190
- 1e Seebach D, Jaeschke G, Wang YM. Angew. Chem., Int. Ed. Engl. 1995; 34: 2395
- 1f Seebach D, Dahinden R, Marti RT, Beck AK, Plattner DA, Kuhnle FN. M. J. Org. Chem. 1995; 60: 5364
- 1g Seebach D, Dahinden R, Marti RE, Beck AK, Plattner DA, Kuhnle NM. J. Org. Chem. 1995; 60: 1788
- 1h Hafner A, Duthaler RO, Marti R, Rihs G, Rothestreit P, Schwarzenbach F. J. Am. Chem. Soc. 1992; 114: 2321
- 1i Duthaler RO, Hafner A. Chem. Rev. 1992; 92: 807
- 2a Anderson CD, Dudding T, Gordillo R, Houk KN. Org. Lett. 2008; 10: 2749
- 2b Rueping M, Sugiono E, Moreth SA. Adv. Synth. Catal. 2007; 349: 759
- 2c McGilvra JD, Unni AK, Modi K, Rawal VH. Angew. Chem. Int. Ed. 2006; 45: 6130
- 2d Zhang X, Du HF, Wang Z, Wu YD, Ding KL. J. Org. Chem. 2006; 71: 2862
- 2e Akiyama T, Itoh J, Fuchibe K. Adv. Synth. Catal. 2006; 348: 999
- 2f Thadani AN, Stankovic AR, Rawal VH. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5846
- 2g Huang Y, Unni AK, Thadani AN, Rawal VH. Nature 2003; 424: 146
- 2h Pihko PM. Hydrogen Bonding in Organic Synthesis . Wiley-VCH; Weinheim: 2009
- 2i Doyle AG, Jacobsen EN. Chem. Rev. 2007; 107: 5713
- 2j Schreiner PR. Chem. Soc. Rev. 2003; 32: 289
- 3a Zhang ZG, Schreiner PR. Chem. Soc. Rev. 2009; 38: 1187
- 3b Connon SJ. Synlett 2009; 354
- 3c Taylor MS, Jacobsen EN. Angew. Chem. Int. Ed. 2006; 45: 1520
- 3d Connon SJ. Chem.–Eur. J. 2006; 12: 5418
- 3e Takemoto Y. Org. Biomol. Chem. 2005; 3: 4299
- 4 Gherase D, Roussel C. Cent. Eur. J. Chem. 2012; 10: 1066
- 5 Seebach D, Hayakawa M, Sakaki J, Schweizer WB. Tetrahedron 1993; 49: 1711
- 6 Ma JA, Cahard D. Angew. Chem. Int. Ed. 2004; 43: 4566
- 7 Jakab G, Tancon C, Zhang ZG, Lippert KM, Schreiner PR. Org. Lett. 2012; 14: 1724
- 8a Unni AK, Takenaka N, Yamamoto H, Rawal VH. J. Am. Chem. Soc. 2005; 127: 1336
- 8b Toda F, Tanaka K, Infantes L, Foces-Foces CN, Claramunt RM, Elguero J. Chem. Commun. 1995; 1453
- 9 Crystal data for C40H34F6N2O3S·C4H8O2 [(4R,5S)-5·EtOAc]: M = 824.86, monoclinic, P21 (No. 4), a = 9.9244(7), b = 9.0175(6), c = 23.8125(19) Å, β = 100.869(3)°, V = 2092.8(3) Å3, D c = 1.309 g cm–3, μ = 1.319 mm–1, F(000) = 860, Z = 2, λ = 1.54178 Å, T = 223(2) K, 15416 reflections collected (± h, ± k, ± l), [(sin θ)/λ] = 0.60 Ǻ–1, 5036 independent (R int = 0.092), and 3698 observed reflections [I ≥ 2σ(I)], 590 refined parameters, R = 0.063, wR2 = 0.177, GoF = 1.012, Flack parameter –0.03(4); CCDC 855621. Crystal data for C47H41F6N3O2S (15): M = 825.89, orthorhombic, P212121 (No. 19), a = 9.6586(1), b = 17.4493(3), c = 24.9234(5) Å, V = 4200.49(12) Å3, D c = 1.306 g cm–3, μ = 0.146 mm–1, F(000) = 1720, Z = 4, λ = 0.71073 Å, T = 223(2) K, 20080 reflections collected (± h, ± k, ± l), [(sin θ)/λ] = 0.59 Ǻ–1, 7248 independent (R int = 0.055), and 6252 observed reflections [I ≥ 2σ(I)], 599 refined parameters, R = 0.071, wR2 = 0.158, GoF = 1.000, Flack parameter –0.05(15); CCDC 855620. Data set was collected with a Nonius KappaCCD diffractometer. The supplementary crystallographic data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk]
- 10a Data collection: COLLECT . Nonius B.V; Delft: 1998
- 10b Data reduction Denzo-SMN: Otwinowski Z, Minor W. Methods Enzymol. 1997; 276: 307
- 10c Absorption correction Denzo: Otwinowski Z, Borek D, Majewski W, Minor W. Acta Crystallogr., Sect. A 2003; 59: 228
- 10d Structure solution SHELXS-97: Sheldrick GM. Acta Crystallogr., Sect. A 1990; 46: 467
- 10e Structure refinement SHELXL-97: Sheldrick GM. Acta Crystallogr. Sect. A 2008; 64: 112
- 10f Graphics: Graphics XP . Bruker AXS; Rheinstetten: 2000
- 11 Bondi A. J. Phys. Chem. 1964; 68: 441
- 12a Gan CS. Can. J. Chem. 2008; 86: 261
- 12b Ax A, Schaal W, Vrang L, Samuelsson B, Hallberg A, Karlen A. Bioorg. Med. Chem. 2005; 13: 755
- 13a Berkessel A, Seelig C. Synthesis 2009; 2113
- 13b Martin NJ. A, Ozores L, List B. J. Am. Chem. Soc. 2007; 129: 8976
- 14a Jones CR, Pantos CG, Morrison AJ, Smith MD. Angew. Chem. Int. Ed. 2009; 48: 7391
- 14b Raheem IT, Thiara PS, Jacobsen EN. Org. Lett. 2008; 10: 1577
- 14c Martin NJ. A, Cheng X, List B. J. Am. Chem. Soc. 2008; 130: 13862
- 14d Uyeda C, Jacobsen EN. J. Am. Chem. Soc. 2008; 130: 9228
- 14e Raheem IT, Thiara PS, Peterson EA, Jacobsen EN. J. Am. Chem. Soc. 2007; 129: 13404
- 14f Taylor MS, Jacobsen EN. J. Am. Chem. Soc. 2004; 126: 10558
- 15a Shi M, Liu XG. Org. Lett. 2008; 10: 1043
- 15b Sohtome Y, Takemura N, Takagi R, Hashimoto Y, Nagasawa K. Tetrahedron 2008; 64: 9423
- 15c Sohtome Y, Tanatani A, Hashimoto Y, Nagasawa K. Tetrahedron Lett. 2004; 45: 5589
- 16 Mansilla J, Saa JM. Molecules 2010; 15: 709
- 17 Herrera RP, Sgarzani V, Bernardi L, Ricci A. Angew. Chem. Int. Ed. 2005; 44: 6576
Programs used:
-
References
- 1a Seebach D, Beck AK, Heckel A. Angew. Chem. Int. Ed. 2001; 40: 92
- 1b Hintermann L, Togni A. Angew. Chem. Int. Ed. 2000; 39: 4359
- 1c Seebach D, Pichota A, Beck AK, Pinkerton AB, Litz T, Karjalainen J, Gramlich V. Org. Lett. 1999; 1: 55
- 1d Jaeschke G, Seebach D. J. Org. Chem. 1998; 63: 1190
- 1e Seebach D, Jaeschke G, Wang YM. Angew. Chem., Int. Ed. Engl. 1995; 34: 2395
- 1f Seebach D, Dahinden R, Marti RT, Beck AK, Plattner DA, Kuhnle FN. M. J. Org. Chem. 1995; 60: 5364
- 1g Seebach D, Dahinden R, Marti RE, Beck AK, Plattner DA, Kuhnle NM. J. Org. Chem. 1995; 60: 1788
- 1h Hafner A, Duthaler RO, Marti R, Rihs G, Rothestreit P, Schwarzenbach F. J. Am. Chem. Soc. 1992; 114: 2321
- 1i Duthaler RO, Hafner A. Chem. Rev. 1992; 92: 807
- 2a Anderson CD, Dudding T, Gordillo R, Houk KN. Org. Lett. 2008; 10: 2749
- 2b Rueping M, Sugiono E, Moreth SA. Adv. Synth. Catal. 2007; 349: 759
- 2c McGilvra JD, Unni AK, Modi K, Rawal VH. Angew. Chem. Int. Ed. 2006; 45: 6130
- 2d Zhang X, Du HF, Wang Z, Wu YD, Ding KL. J. Org. Chem. 2006; 71: 2862
- 2e Akiyama T, Itoh J, Fuchibe K. Adv. Synth. Catal. 2006; 348: 999
- 2f Thadani AN, Stankovic AR, Rawal VH. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5846
- 2g Huang Y, Unni AK, Thadani AN, Rawal VH. Nature 2003; 424: 146
- 2h Pihko PM. Hydrogen Bonding in Organic Synthesis . Wiley-VCH; Weinheim: 2009
- 2i Doyle AG, Jacobsen EN. Chem. Rev. 2007; 107: 5713
- 2j Schreiner PR. Chem. Soc. Rev. 2003; 32: 289
- 3a Zhang ZG, Schreiner PR. Chem. Soc. Rev. 2009; 38: 1187
- 3b Connon SJ. Synlett 2009; 354
- 3c Taylor MS, Jacobsen EN. Angew. Chem. Int. Ed. 2006; 45: 1520
- 3d Connon SJ. Chem.–Eur. J. 2006; 12: 5418
- 3e Takemoto Y. Org. Biomol. Chem. 2005; 3: 4299
- 4 Gherase D, Roussel C. Cent. Eur. J. Chem. 2012; 10: 1066
- 5 Seebach D, Hayakawa M, Sakaki J, Schweizer WB. Tetrahedron 1993; 49: 1711
- 6 Ma JA, Cahard D. Angew. Chem. Int. Ed. 2004; 43: 4566
- 7 Jakab G, Tancon C, Zhang ZG, Lippert KM, Schreiner PR. Org. Lett. 2012; 14: 1724
- 8a Unni AK, Takenaka N, Yamamoto H, Rawal VH. J. Am. Chem. Soc. 2005; 127: 1336
- 8b Toda F, Tanaka K, Infantes L, Foces-Foces CN, Claramunt RM, Elguero J. Chem. Commun. 1995; 1453
- 9 Crystal data for C40H34F6N2O3S·C4H8O2 [(4R,5S)-5·EtOAc]: M = 824.86, monoclinic, P21 (No. 4), a = 9.9244(7), b = 9.0175(6), c = 23.8125(19) Å, β = 100.869(3)°, V = 2092.8(3) Å3, D c = 1.309 g cm–3, μ = 1.319 mm–1, F(000) = 860, Z = 2, λ = 1.54178 Å, T = 223(2) K, 15416 reflections collected (± h, ± k, ± l), [(sin θ)/λ] = 0.60 Ǻ–1, 5036 independent (R int = 0.092), and 3698 observed reflections [I ≥ 2σ(I)], 590 refined parameters, R = 0.063, wR2 = 0.177, GoF = 1.012, Flack parameter –0.03(4); CCDC 855621. Crystal data for C47H41F6N3O2S (15): M = 825.89, orthorhombic, P212121 (No. 19), a = 9.6586(1), b = 17.4493(3), c = 24.9234(5) Å, V = 4200.49(12) Å3, D c = 1.306 g cm–3, μ = 0.146 mm–1, F(000) = 1720, Z = 4, λ = 0.71073 Å, T = 223(2) K, 20080 reflections collected (± h, ± k, ± l), [(sin θ)/λ] = 0.59 Ǻ–1, 7248 independent (R int = 0.055), and 6252 observed reflections [I ≥ 2σ(I)], 599 refined parameters, R = 0.071, wR2 = 0.158, GoF = 1.000, Flack parameter –0.05(15); CCDC 855620. Data set was collected with a Nonius KappaCCD diffractometer. The supplementary crystallographic data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk]
- 10a Data collection: COLLECT . Nonius B.V; Delft: 1998
- 10b Data reduction Denzo-SMN: Otwinowski Z, Minor W. Methods Enzymol. 1997; 276: 307
- 10c Absorption correction Denzo: Otwinowski Z, Borek D, Majewski W, Minor W. Acta Crystallogr., Sect. A 2003; 59: 228
- 10d Structure solution SHELXS-97: Sheldrick GM. Acta Crystallogr., Sect. A 1990; 46: 467
- 10e Structure refinement SHELXL-97: Sheldrick GM. Acta Crystallogr. Sect. A 2008; 64: 112
- 10f Graphics: Graphics XP . Bruker AXS; Rheinstetten: 2000
- 11 Bondi A. J. Phys. Chem. 1964; 68: 441
- 12a Gan CS. Can. J. Chem. 2008; 86: 261
- 12b Ax A, Schaal W, Vrang L, Samuelsson B, Hallberg A, Karlen A. Bioorg. Med. Chem. 2005; 13: 755
- 13a Berkessel A, Seelig C. Synthesis 2009; 2113
- 13b Martin NJ. A, Ozores L, List B. J. Am. Chem. Soc. 2007; 129: 8976
- 14a Jones CR, Pantos CG, Morrison AJ, Smith MD. Angew. Chem. Int. Ed. 2009; 48: 7391
- 14b Raheem IT, Thiara PS, Jacobsen EN. Org. Lett. 2008; 10: 1577
- 14c Martin NJ. A, Cheng X, List B. J. Am. Chem. Soc. 2008; 130: 13862
- 14d Uyeda C, Jacobsen EN. J. Am. Chem. Soc. 2008; 130: 9228
- 14e Raheem IT, Thiara PS, Peterson EA, Jacobsen EN. J. Am. Chem. Soc. 2007; 129: 13404
- 14f Taylor MS, Jacobsen EN. J. Am. Chem. Soc. 2004; 126: 10558
- 15a Shi M, Liu XG. Org. Lett. 2008; 10: 1043
- 15b Sohtome Y, Takemura N, Takagi R, Hashimoto Y, Nagasawa K. Tetrahedron 2008; 64: 9423
- 15c Sohtome Y, Tanatani A, Hashimoto Y, Nagasawa K. Tetrahedron Lett. 2004; 45: 5589
- 16 Mansilla J, Saa JM. Molecules 2010; 15: 709
- 17 Herrera RP, Sgarzani V, Bernardi L, Ricci A. Angew. Chem. Int. Ed. 2005; 44: 6576
Programs used:
