UPPRTING INFRMATIN ynthesis of sulfur-containing exo-bicyclic dienes and their Diels-Alder reactions to access thiacycle-fused polycyclic systems Thomas Castanheiro, a Angèle choenfelder, a Morgan Donnard, a Isabelle Chataigner, b,c and Mihaela Gulea a * a Université de trasbourg, CNR, Laboratoire d Innovation Thérapeutique, LIT UMR 7200, 67000 trasbourg, France b Normandie Université, INA Rouen, CNR, CBRA UMR 6014, 76000 Rouen, France c orbonne Université, UPMC Univ. Paris 6, CNR UMR 7616 Laboratoire de Chimie Théorique 75005 Paris, France Table of contents: 1. X-ray structures 2 2. Theoretical study 7 2.1. Total energy and cartesian coordinates for D1, 3b, 3f 7 2.2. Cycloaddition between D1 and 3b 10 2.3. Cycloaddition between D1 and 3f 19 2.4. Computed conformations for 10fA-major, 10fB-minor 28 2.5. Validation of the DFT methods for cycloaddition of 3b and D1 30 3. 1 H and 13 C NMR spectra 31
1. X-ray structures of 4bA, 4 ca, 4fA, and 8b CCDC 1562845, 1562846, 1562847 and 1580662 contain the supplementary crystallographic data for this paper. These data are provided free of charge by the Cambridge Crystallographic Data Centre. 4bA: CCDC 1562845; Formula: C19 H18 3 1; Unit Cell Parameters: a 17.9400(6) b 17.9400(6) c 8.4256(4) P31c Bond precision: C-C = 0.0059 A Wavelength=1.54178 Cell: a=17.9400(6) b=17.9400(6) c=8.4256(4) alpha=90 beta=90 gamma=120 Temperature: 173 K Calculated Reported Volume 2348.4(2) 2348.42(19) pace group P 3 1 c P 3 1 c Hall group P 3-2c P 3-2c Moiety formula C19 H18 3 C19 H18 3 um formula C19 H18 3 C19 H18 3 Mr 326.39 326.39 Dx,g cm-3 1.385 1.385 Z 6 6 Mu (mm-1) 1.942 1.942 F000 1032.0 1032.0 F000' 1036.85 h,k,lmax 21,21,10 21,20,10 Nref 2774[ 1396] 2451 Tmin,Tmax 0.890,0.925 0.651,0.753 Tmin' 0.517 Correction method= # Reported T Limits: Tmin=0.651 Tmax=0.753 AbsCorr = MULTI-CAN Data completeness= 1.76/0.88 Theta(max)= 66.658 R(reflections)= 0.0377( 2128) wr2(reflections)= 0.0894( 2451) = 1.057 Npar= 208
Figure 1. X-ray structure of 4bA (R1 = 3.7%) 4 ca: CCDC 1562846; Formula: C14 H16 4 1; Unit Cell Parameters: a 8.1274(3) b 17.4435(7) c 8.9072(4) P21/c Bond precision: C-C = 0.0016 A Wavelength=0.71073 Cell: a=8.1274(3) b=17.4435(7) c=8.9072(4) alpha=90 beta=103.903(1) gamma=90 Temperature: 173 K Calculated Reported Volume 1225.78(9) 1225.78(9) pace group P 21/c P 21/c Hall group -P 2ybc -P 2ybc Moiety formula C14 H16 4 C14 H16 4 um formula C14 H16 4 C14 H16 4 Mr 280.33 280.33 Dx,g cm-3 1.519 1.519 Z 4 4 Mu (mm-1) 0.272 0.272 F000 592.0 592.0 F000' 592.79 h,k,lmax 12,26,13 12,26,13 Nref 4634 4631 Tmin,Tmax 0.922,0.957 0.702,0.747 Tmin' 0.922 Correction method= # Reported T Limits: Tmin=0.702 Tmax=0.747 AbsCorr = MULTI-CAN Data completeness= 0.999 Theta(max)= 33.027 R(reflections)= 0.0408( 3771) wr2(reflections)= 0.1094( 4631) = 1.051 Npar= 176
Figure 2. X-ray structure of 4 ca (R1 = 4.0%) Crystals obtained from 4fA were of lower quality, however it was possible to get the X-ray structure. 4fA: CCDC 1580662; Formula: C20 H20 3 1; Unit Cell Parameters: a 11.2915(5) b 7.6426(2) c 37.0847(16) Pbca Bond precision: C-C = 0.00576 A Wavelength=0.71073 Cell: a=11.2915(5) b=7.6426(2) c=37.0847(16) alpha=90 beta=90 gamma=90 Temperature: 173 K Calculated Reported Volume 3200.3(2) 3200.3(2) pace group P b c a P b c a Hall group -P 2ac 2ab -P 2ac 2ab Moiety formula C20 H20 3 C20 H20 3 um formula C20 H20 3 C20 H20 3 Mr 340.42 340.42 Dx,g cm-3 1.413 1.413 Z 8 8 Mu (mm-1) 0.218 0.218 F000 1440.0 1440.0 F000' 1441.63 1441.63 h,k,lmax 14,9,48 14,9,48 Nref 3665 3559 Tmin,Tmax 0.964,0.991 Tmin' 0.897 Correction method= not given
Data completeness= 0.971 Theta(max)= 27.491 R(reflections)= 0.1116( 1999) wr2(reflections)= 0.2266( 3559) = 1.114 Npar= 217 Figure 3. X-ray structure of 4fA (R1 = 11%) 8b: CCDC 1562847; Formula: C23 H19 N3 2 1; Unit Cell Parameters: a 8.68580(10) b 25.2666(4) c 8.42000(10) P21/c Bond precision: C-C = 0.0020 A Wavelength=0.71073 Cell: a=8.6858(1) b=25.2666(4) c=8.4200(1) alpha=90 beta=93.074(1) gamma=90 Temperature: 173 K Calculated Reported Volume 1845.20(4) 1845.20(4) pace group P 21/c P 21/c Hall group -P 2ybc -P 2ybc Moiety formula C23 H19 N3 2 C23 H19 N3 2 um formula C23 H19 N3 2 C23 H19 N3 2 Mr 401.47 401.47 Dx,g cm-3 1.445 1.445 Z 4 4 Mu (mm-1) 0.202 0.202 F000 840.0 840.0 F000' 840.81 h,k,lmax 11,32,10 11,32,10 Nref 4235 4230 Tmin,Tmax 0.908,0.960 Tmin' 0.904 Correction method= Not given
Data completeness= 0.999 Theta(max)= 27.487 R(reflections)= 0.0433( 3585) wr2(reflections)= 0.1367( 4230) = 1.118 Npar= 262 Figure 4. X-ray structure of 8b (R1 = 4.3%)
2. Theoretical study 2.1. Total energy and cartesian coordinates for D1, 3b, 3f, Figure 5. D1 Electronic Energy = - 379.181444 a.u. um of electronic and thermal free energies = - 379.153889 a.u. Number of imaginary frequencies: 0 C 0.021332 0.000000 0.018241 C 0.022428 0.000000 1.349291 H 0.848575 0.000000-0.677660 H 0.850844 0.000000 2.043773 C -1.397105 0.000000 1.809114-1.837274 0.000000 2.918765-2.202300 0.000000 0.686441 C -1.398564 0.000000-0.439204-1.841881 0.000000-1.547401 Figure 6. 3b Electronic Energy = - 979.236666 a.u. um of electronic and thermal free energies = - 979.004963 a.u. Number of imaginary frequencies: 0 C 1.629547-1.194011 3.175994 C 1.318153-0.648770 1.993728 C 2.235395-0.484745 0.850841 C 3.510234-0.079373 0.991243 C 1.519419-0.737884-0.457936-0.284698-0.601659-0.133720 C -0.088146-0.214842 1.652966 C -1.124639-0.889059 2.546872 C -0.708730-0.701899 4.009611 C 0.636904-1.380251 4.291309 C 4.522567 0.132405-0.055936 C 4.563926-0.602359-1.249686 C 5.539540-0.350872-2.210354 C 6.499987 0.634706-1.996957
C 6.485750 1.359853-0.806206 C 5.512524 1.105592 0.153324 H 2.639683-1.566334 3.336189 H 0.488615-2.458540 4.445440 H 1.062625-1.002743 5.229127 H -1.476536-1.101276 4.679621 H -0.628445 0.371614 4.223146 H -1.173443-1.956964 2.302119 H -2.117656-0.464171 2.369458 H -0.169720 0.873462 1.765280 H 3.832202 0.170757 2.000926 H 5.507904 1.673423 1.080105 H 7.235487 2.123773-0.624584 H 7.259561 0.830049-2.747272 H 5.553318-0.933952-3.126128 H 3.848135-1.398305-1.420535 H 1.714065-1.748572-0.828407 H 1.821263-0.022782-1.227311
Figure 7. 3f Electronic Energy = - 1018.543832 a.u. um of electronic and thermal free energies = - 1018.284267 a.u. Number of imaginary frequencies: 0 C -0.337803 0.957658 0.356254 C 0.729706 1.117934-0.442174 C 0.550389 1.443894-1.884414 C -0.347269 0.743275-2.604401 C 1.428762 2.527194-2.471635 C 2.909634 2.308180-2.158694 3.244251 2.305174-0.376552 C 2.140446 0.914882 0.081705 C 2.200992 0.758913 1.604014 C 1.077266-0.143668 2.107417 C -0.276051 0.487698 1.783194 C -0.736465 0.950745-4.015353 C -0.860030-0.159244-4.862538 C -1.229567-0.006301-6.194916 C -1.498076 1.262850-6.705337 C -1.405695 2.372931-5.868757 C -1.033373 2.217332-4.535986 H -1.086918-0.228941 1.960109 H -0.468674 1.332937 2.459279 H 1.177484-0.307823 3.185036 H 2.098811 1.747131 2.071089 H 3.182336 0.366113 1.887741 H 2.557843 0.015581-0.392108 H -1.323775 1.163863-0.055357 H 1.149445-1.126061 1.623370 H 1.306964 2.563202-3.557418 H 1.127811 3.502807-2.069293 H 3.510729 3.117370-2.581489 H 3.260529 1.367720-2.597806 H -0.834112-0.096897-2.111652 H -0.653567-1.150862-4.468577 H -1.308658-0.878759-6.836356 H -1.786457 1.384769-7.744676 H -1.630937 3.363346-6.252454 H -0.992328 3.084203-3.883305
2.2. Cycloaddition between D1 and 3b Figure 8. T_5_top_endo Electronic Energy = - 1358.410416 a.u. (DE e = 4.83 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.126065 a.u. (DG = 20.57 kcal.mol -1 ) Number of imaginary frequencies: 1 (-521.6630) C 0.011208-0.272934 0.572288 C 0.949792-2.133966 0.335173 C 2.221622-2.145343 0.917657 C 2.549658-0.038273 1.930864 C 1.345944 0.050102 2.623424 C 0.126120-0.060405 1.947384 C 0.074102-2.935180 1.227881 0.772590-3.189563 2.385908 C 2.122740-2.867598 2.186803 C -1.078722-0.155965 2.853847-0.544396 0.695530 4.380921 C 1.173042 0.122671 4.126067 C -1.354045-0.264955-0.089008 C -2.540163-0.395964 0.878375 C -2.325290 0.395764 2.174070 C 3.908738-0.015831 2.483575 C 4.244289-0.532214 3.743209 C 5.556429-0.478268 4.201376 C 6.556188 0.087598 3.414486 C 6.240931 0.590849 2.153054 C 4.931989 0.530911 1.692101-1.052604-3.318945 1.070401 2.950517-3.191310 2.993150 H 0.799497 0.142360-0.051105 H 2.509499 0.261605 0.888189 H 0.759209-2.142675-0.730386 H 3.172760-2.033008 0.418491 H 4.691781 0.923390 0.706914 H 7.014675 1.026343 1.528864 H 7.577986 0.129016 3.778236 H 5.798253-0.893789 5.174076 H 3.493833-1.015849 4.354677 H 1.306916-0.859518 4.593326 H 1.867622 0.826980 4.589078 H -1.259321-1.210963 3.103083 H -1.412706-1.049623-0.850821 H -2.187710 1.463815 1.964205 H -3.196279 0.294458 2.828382 H -3.447717-0.050805 0.373643 H -2.692375-1.451200 1.124275
H -1.428467 0.689259-0.628241 Figure 9. cycloadduct_5_top_endo Electronic Energy = - 1358.484230 a.u. (ΔE e = -41.49 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.196039 a.u. (ΔG r = -23.33 kcal.mol -1 ) Number of imaginary frequencies: 0 C -0.566174-1.075753-1.831961 C -1.549588 0.091786-1.698466 C -1.340965 0.699341-0.343659 C -0.129655 0.892956 0.172327 C 1.114747 0.552397-0.623108 C 0.907681-0.699889-1.573731 C -0.797239-2.198804-0.825988 0.419730-2.725090-0.454199 C 1.457772-1.992471-1.001173 C -2.532558 1.184326 0.422104 C -3.461212 1.937983-0.534909 C -3.904605 1.032943-1.719682 C -3.032436-0.224412-1.920633 C -0.095892 1.643923 1.478435-1.822148 2.200953 1.776333 C 2.374539 0.470069 0.217852 C 3.506039 1.202381-0.139540 C 4.669414 1.136650 0.624907 C 4.710780 0.334405 1.761160 C 3.585592-0.402446 2.127035 C 2.428013-0.333942 1.360587 2.576633-2.405486-0.996966-1.818550-2.651239-0.400867 H -1.247349 0.832364-2.457253 H 1.257078 1.390883-1.318338 H -0.656812-1.537534-2.824336 H 1.456044-0.504053-2.496718 H 3.479981 1.832935-1.025075 H 5.541475 1.712433 0.331263 H 5.615728 0.280196 2.357865 H 3.610669-1.036152 3.007744 H 1.559893-0.920845 1.652443 H 0.246231 1.023118 2.310886 H 0.567063 2.513110 1.422948 H -3.071497 0.336368 0.863216 H -3.186643-0.625822-2.928100 H -3.336264-1.007765-1.222449 H -2.915563 2.811822-0.907272
H -4.335969 2.319057-0.000167 H -4.939187 0.707969-1.574262 H -3.897785 1.632204-2.636943 Figure 10. T_5_below_endo Electronic Energy = - 1358.404195 a.u. (DE e = 8.73 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.120017 a.u. (DG = 24.37 kcal.mol -1 ) Number of imaginary frequencies: 1 (-534.6373) C 1.670890-1.702244 0.519464 C 2.431334 0.063914 1.726644 C 1.274786 0.474108 2.387791 C 0.058110 0.724762 1.740941 C -0.008041 0.712509 0.341445 C 0.446784-1.360851-0.061311 C 1.383445-2.563828 1.672969 0.008316-2.579832 1.860944 C -0.604801-2.003707 0.763896 C 1.225933 0.530352 3.897491 C 2.155495-0.493952 4.538146 C 3.570202-0.243109 4.004912 C 3.659751-0.398818 2.477613-0.538025 0.383393 4.352091 C -1.134215 0.781218 2.668430 C -1.149720 1.083535-0.524251 C -0.838922 1.705624-1.744190 C -1.833825 2.098737-2.630946 C -3.171360 1.864675-2.319422 C -3.495705 1.234838-1.120849 C -2.499344 0.847638-0.230018-1.793183-2.062747 0.609582 2.118902-3.188095 2.389821 H -2.785292 0.330184 0.674431 H -4.533793 1.033737-0.876865 H -3.953704 2.165715-3.008709 H -1.565775 2.585623-3.563181 H 0.202747 1.891662-1.995021 H 0.937179 0.947533-0.141028 H 2.604255 0.427571 0.719347 H 3.823710-1.457703 2.245469 H 4.535127 0.137489 2.094572 H 4.277632-0.930572 4.477120 H 3.877685 0.771544 4.288421 H 1.822819-1.509029 4.298619 H 2.140735-0.389419 5.627455
H 1.566871 1.529794 4.199432 H -1.617623 1.763363 2.635048 H 2.619274-1.784140 0.007654 H 0.269482-1.196187-1.115440 H -1.876107 0.026267 2.402875 Figure 11. cycloadduct_5_below_endo Electronic Energy = - 1358.496570 a.u. (DE e = -49.23 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.206063 a.u. (DG r = -29.62 kcal.mol -1 ) Number of imaginary frequencies: 0 C 1.797055-0.787308-1.038316 C 2.031098-0.416818 0.442524 C 1.494550 0.946680 0.789225 C 0.807777 1.751487-0.019309 C 0.428942 1.392004-1.427280 C 1.463760 0.369943-1.991727 C 0.768050-1.836184-1.445377 0.418336-1.590906-2.764031 C 0.884524-0.364956-3.181330 C 1.711867 1.419012 2.201978 C 1.203124 0.373483 3.200918 C 1.848593-0.984297 2.904439 C 1.543061-1.451141 1.478577 0.860278 3.042468 2.319539 C 0.317655 3.043534 0.570653 C -1.021822 0.919038-1.514880 C -1.779605 1.228609-2.648179 C -3.083345 0.760451-2.780694 C -3.650659-0.021707-1.777251 C -2.909093-0.323991-0.638630 C -1.605929 0.148258-0.507117 0.788255-0.006762-4.317755 0.354016-2.798146-0.873513 H -1.043084-0.081068 0.392490 H -3.342165-0.930090 0.150630 H -4.664989-0.393131-1.882569 H -3.653486 1.003858-3.671565 H -1.339338 1.826102-3.441646 H 0.511160 2.284034-2.059196 H 3.122264-0.353674 0.571345 H 0.464953-1.604090 1.369176 H 2.011142-2.419987 1.281970 H 1.487556-1.731318 3.618289 H 2.936005-0.913463 3.047668 H 0.112893 0.296858 3.107279 H 1.419153 0.692205 4.225675
H 2.784420 1.577091 2.379269 H 0.741190 3.907295 0.046790 H 2.726913-1.243636-1.406835 H 2.353646 0.920388-2.302320 H -0.773652 3.114293 0.511985
Figure 12. T_5_top_exo Electronic Energy = - 1358.405117 a.u. (DE e = 8.15 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.121297 a.u. (DG = 23.57 kcal.mol -1 ) Number of imaginary frequencies: 1 (-512.6361) C 2.427943-0.324726 1.055012 C 2.875121-2.349260 0.565482 C 3.212925-2.794166 1.839937 C 2.324109-2.865801 2.919588 C 1.002870-2.455808 2.785409 C 1.501371-0.250074 2.098111 C 1.676422-0.005747-0.188673 0.334087 0.035293 0.114506 C 0.186717 0.026833 1.507446 C 4.659688-2.973119 2.237503 C 5.520432-3.449132 1.076116 C 5.343396-2.448679-0.073435 C 3.890234-2.387405-0.554647 4.578235-4.057456 3.705437 C 3.020225-3.245870 4.211701 C -0.014125-2.354090 3.838862 C -1.354039-2.580302 3.493084 C -2.362687-2.496914 4.445375 C -2.052601-2.166026 5.761853 C -0.728746-1.909853 6.115643 C 0.280049-2.000673 5.164358 2.081444 0.179155-1.303296-0.883272 0.216393 2.012712 H 1.850278-2.516707 0.239812 H 3.666780-3.284000-1.148947 H 5.990994-2.716205-0.913600 H 5.667676-1.455262 0.263816 H 5.200393-4.450680 0.764121 H 6.570981-3.513098 1.375056 H 5.052356-2.000099 2.574589 H 3.259181-2.363096 4.816901 H 0.580555-2.548424 1.788664 H -1.604910-2.816055 2.463087 H -3.392819-2.677569 4.156594 H -2.838525-2.094458 6.506773 H -0.482689-1.632201 7.135654 H 1.298440-1.769596 5.454870 H 1.695803-0.012027 3.132757 H 3.469778-0.039013 1.121304 H 3.735198-1.538202-1.227839 H 2.423604-3.927594 4.821598
Figure 13. cycloadduct_5_top_exo Electronic Energy = - 1358.492994 a.u. (DE e = -49.99 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.204629 a.u. (DG r = -28.73 kcal.mol -1 ) Number of imaginary frequencies: 0 C -0.215870 0.949023-1.137959 C 0.006291 1.498678 0.246540 C 0.953425 1.076530 1.082145 C 2.000218 0.040972 0.776040 C 2.373233-0.745046 2.053611 C 1.156237-0.873850 2.971691 C 0.694235 0.499050 3.504023 C 0.946597 1.633390 2.477983-0.323707 2.959810 2.463566 C -0.914714 2.564390 0.775046 C -1.632574 0.409282-1.293617 C -2.402296 0.750238-2.405609 C -3.679156 0.216409-2.575626 C -4.198523-0.666880-1.633369 C -3.437290-1.009761-0.516479 C -2.164721-0.472753-0.348414 H -1.582322-0.727173 0.534503 H -3.836973-1.693062 0.226405 H -5.191597-1.084351-1.765174 H -4.266745 0.493038-3.445496 H -2.000781 1.437771-3.145727 H -0.085613 1.759141-1.867074 H 2.897126 0.573258 0.425931 H 2.775966-1.725415 1.781453 H 3.175229-0.217995 2.583277 H 0.336696-1.343916 2.411550 H 1.377649-1.543153 3.808031 H -0.373030 0.463262 3.739602 H 1.219670 0.736417 4.435016 H 1.911609 2.107002 2.692354 H -1.954097 2.222538 0.798528 H -0.871543 3.466331 0.155298 C 0.806624-0.145374-1.497554 C 1.516590-0.892578-0.362274 C 2.740405-1.423519-1.076605 C 1.980490 0.300304-2.348804 H 0.926030-1.713919 0.048715 H 0.296124-0.890189-2.122929 3.444938-2.349207-0.806470 3.017609-0.592140-2.150377 2.070113 1.210784-3.115710
Figure 14. T_5_below_exo Electronic Energy = - 1358.397045 a.u. (DE e = 13.22 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.114744 a.u. (DG = 27.68 kcal.mol -1 ) Number of imaginary frequencies: 1 (-516.7378) C -0.172149-0.056321 0.088893 C -0.101995 0.263342 1.441220 C 1.122297 0.300093 2.130323 C 2.336579-0.096153 1.588648 C 3.526199-0.292278 2.489689 C 3.084522-0.803683 3.862349 C 2.112250 0.167934 4.532130 C 0.967777 0.619417 3.605012-0.688791-0.041840 4.032479 C -1.289876 0.421734 2.371022 C -1.409091-0.122521-0.723482 C -1.454269 0.597870-1.922329 C -2.587370 0.573791-2.728797 C -3.690290-0.191118-2.359276 C -3.647743-0.937010-1.183051 C -2.516989-0.904637-0.374701 H -2.490617-1.523042 0.517484 H -4.492266-1.557368-0.900050 H -4.571794-0.220132-2.991675 H -2.602108 1.141025-3.653883 H -0.589513 1.180946-2.226753 H 0.706993 0.209726-0.495748 H 2.536571 0.098054 0.538177 H 4.227851-0.985694 2.016869 H 4.059336 0.663412 2.599084 H 2.610044-1.785663 3.751700 H 3.956028-0.949585 4.507100 H 1.704715-0.274281 5.446481 H 2.669502 1.058475 4.843562 H 0.882905 1.711532 3.676531 H -2.142601-0.199464 2.107989 H -1.628584 1.465081 2.371657 C 0.598252-2.146617 0.189608 C 1.786435-2.180481 0.912824 C 2.886285-2.304162-0.065627 C 0.960883-2.254509-1.242894 H 1.906905-2.562394 1.915008 H -0.360450-2.510031 0.527625 4.065538-2.451786 0.105163 2.348615-2.197704-1.337011 0.275080-2.364075-2.217301
Figure 15. cycloadduct_5_below_exo Electronic Energy = - 1358.491726 a.u. (DE e = -46.19 kcal.mol -1 ) um of electronic and thermal free energies = - 1358.203444 a.u. (DG r = -27.98 kcal.mol -1 ) Number of imaginary frequencies: 0 C 0.127506 1.287160-1.223977 C 1.257788 0.265622-1.471261 C 1.253633-0.768932-0.383174 C 0.171606-1.207405 0.254025 C -1.199235-0.601113 0.105739 C -1.202554 0.609170-0.857829 C -0.221208 1.948808-2.540156-1.276772 1.261546-3.116628 C -1.797104 0.340660-2.227779 C 2.566678-1.418676-0.042019 C 3.400366-1.592177-1.309757 C 3.710268-0.202878-1.927176 C 2.654372 0.879831-1.604371 2.105138-2.955193 0.844012 C 0.398963-2.369565 1.186907 C -1.768556-0.193688 1.459442 C -3.077512-0.526682 1.807693 C -3.616593-0.106349 3.023095 C -2.849604 0.652738 3.902530 C -1.538896 0.986777 3.563639 C -1.003625 0.564436 2.350770 0.301126 2.867679-3.096116-2.608100-0.468770-2.563715 H 1.040546-0.260490-2.415564 H 2.659200 1.653693-2.376747 H 3.798957-0.314957-3.012487 H 4.684363 0.149741-1.573529 H 2.831786-2.211383-2.012761 H 4.331890-2.125258-1.099287 H 3.123166-0.774333 0.652995 H 0.289488-2.078835 2.236872 H -1.875322-1.351569-0.323932 H -3.681745-1.115724 1.122481 H -4.637363-0.371970 3.279635 H -3.269043 0.980839 4.848209 H -0.932350 1.574326 4.245795 H 0.024099 0.813539 2.096031 H -1.863074 1.376085-0.431810 H 0.450935 2.033675-0.495444 H 2.901281 1.379389-0.658933 H -0.307831-3.181599 0.989493
2.3. Cycloaddition between D1 and 3f Figure 16. T_6_top_endo Electronic Energy = - 1397.712595 a.u. (DE e = 7.96 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.400461 a.u. (DG = 23.65 kcal.mol -1 ) Number of imaginary frequencies: 1 (-486.5643) C -1.358909-4.279981-2.160071 C -0.830345-4.660545-0.937026 C -0.111958-3.719121-0.144931 C 0.138942-2.438513-0.667777 C 0.495028-4.050476 1.203844 H 0.800007-5.630794 2.638340-0.973080-6.388955 1.241069 C -0.895789-6.138694-0.559627 C -2.069016-6.855660-1.227488 C -1.990400-6.673772-2.739629 C -2.087516-5.192895-3.104007 C 0.719354-3.526751-3.262551 C 1.424447-2.883597-2.247745 C 2.343276-3.921549-1.679338 2.050254-5.122249-2.265692 H 1.386742-6.020358 1.019339 H 1.754517-1.852086-2.269461 H 0.171948-3.068988-4.073523 H -0.571202-2.069057-1.399487 H -1.548010-3.229090-2.340950 3.204543-3.823417-0.846712 0.896585-5.803225-4.092549 C 0.682009-1.306278 0.146267 C 2.027915-1.159942 0.496316 C 2.443345-0.063939 1.249789 C 1.526591 0.896891 1.668074 C 0.184052 0.761679 1.321123 C -0.230382-0.326601 0.559535 C 0.583363-5.523648 1.573297 C 1.153825-4.910808-3.329842 H -1.279002-0.425541 0.289988 H -0.540756 1.504875 1.638111 H 1.856043 1.747702 2.256040 H 3.493072 0.037304 1.507135 H 2.753290-1.901272 0.176661 H 0.030975-6.620745-0.898748 H -1.719747-5.028838-4.123155 H -3.014499-6.452099-0.841247 H -2.033854-7.917337-0.965390 H -2.794074-7.226729-3.235329 H -1.044296-7.081147-3.109525
H -3.139527-4.871717-3.105084 H 1.498413-3.619148 1.259966 H -0.104272-3.522144 1.957127 Figure 17. cycloadduct_6_top_endo Electronic Energy = - 1397.793295 a.u. (DE e = -42.68 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.474250 a.u. (DG r = -22.65 kcal.mol -1 ) Number of imaginary frequencies: 0 C -0.472752 2.986345 1.892261 C 0.383188 2.455590 0.918341 C 1.667673 2.987672 0.804660 C 2.085294 4.020010 1.645658 C 1.229789 4.531104 2.615493 C -0.056510 4.007006 2.738499 C -0.177848 1.355668 0.035080 C -0.364921-0.014010 0.684705 C -0.978853-0.941661-0.075642 C -1.064043-2.409451 0.297405-1.148818-2.656629 2.100769 C 0.353360-1.701871 2.465159 C -2.200800-3.151373-0.402598 C -2.088150-2.938374-1.910233 C -2.339797-1.471766-2.251696 C -1.506031-0.467218-1.427167 C -0.343574 0.205765-2.228023 C 0.538518 1.070218-1.308752 C 1.794072 0.215015-1.148567 1.788320-0.802156-2.076675 C 0.614679-0.816751-2.796730 0.459780-1.572794-3.710343 2.707909 0.332567-0.386354 H -2.177504 0.373858-1.216151 H -1.168310 1.729314-0.260079 H -0.776966 0.765818-3.060365 H 0.833847 2.003037-1.803285 H -1.480301 2.587355 1.988987 H -0.737888 4.397928 3.487792 H 1.559666 5.330780 3.271074 H 3.089236 4.419342 1.540074 H 2.365876 2.583942 0.081405 H -0.129674-2.888496-0.031592 H -2.174269-1.300113-3.319446 H -3.171090-2.785623-0.041022 H -2.137829-4.214884-0.152479 H -2.816380-3.560241-2.440344 H -1.096213-3.251783-2.257309
H -3.398765-1.263501-2.059561 H 0.533393-1.782576 3.539461 H 1.195859-2.178004 1.952352 C 0.230402-0.240879 2.050908 H 1.225794 0.219169 2.079829 H -0.373596 0.305932 2.785951 Figure 18. T_6_below_endo Electronic Energy = - 1397.709656 a.u. (DE e = 9.80 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.397004 a.u. (DG = 25.82 kcal.mol -1 ) Number of imaginary frequencies: 1 (-489.7678) C 3.971040 1.074926-0.707960 C 3.613189 0.024226 1.034656 C 5.047093 1.941614-0.527622 C 6.199506 1.024018 1.496300 C 6.017976-0.333531 1.271773 C 4.707291-0.862266 1.088339 C 7.266772-1.212151 1.178734 7.078664-2.674293 0.113194 C 5.598745-3.280035 0.960899 C 4.436883-2.318365 0.767558 C 7.528925 1.716262 1.601369 C 8.717934 0.758074 1.680220 C 8.502426-0.424955 0.742286 C 4.449889 0.051287-1.696317 5.771205 0.280986-1.950032 C 6.155686 1.485458-1.341714 C 2.184737-0.412958 1.058549 C 1.431995-0.073414 2.190533 C 0.097009-0.449609 2.303322 C -0.515011-1.157433 1.271358 C 0.218137-1.481688 0.132304 C 1.557660-1.115814 0.023717 3.851403-0.849645-2.220535 7.243545 1.956341-1.553460 H 2.109431-1.356176-0.878751 H -0.253837-2.019578-0.683931 H -1.558152-1.446422 1.351916 H -0.464362-0.184594 3.193878 H 1.902249 0.482265 2.998204 H 3.728875 0.951011 1.586491 H 5.365744 1.606311 1.865543 H 7.649301 2.351755 0.713442 H 7.510083 2.393210 2.463062 H 9.638384 1.289295 1.421749 H 8.837839 0.388965 2.706765 H 8.375199-0.069327-0.286978
H 9.370358-1.091472 0.756380 H 7.459103-1.602055 2.188561 H 5.028417 2.936606-0.107433 H 2.929212 1.369962-0.739613 H 5.349127-4.254306 0.535300 H 5.828911-3.430357 2.021744 H 3.582808-2.649355 1.370969 H 4.112977-2.381085-0.277910 Figure 19. cycloadduct_6_below_endo Electronic Energy = - 1397.790624 a.u. (DE e = -41.01 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.472689 a.u. (DG r = -21.67 kcal.mol -1 ) Number of imaginary frequencies: 0 C -0.771104 1.372978-0.737278 C -1.175417 0.534579 0.491669 C 0.536308 2.136827-0.460239 C 1.346142 1.520106 0.740263 C 1.187286-0.000345 0.781717 C -0.063715-0.491710 0.687289 C 2.389520-0.889593 1.046235 2.257087-2.484797 0.171134 C 0.676526-2.941596 0.939628 C -0.441465-1.949997 0.633569 C 2.783354 2.080101 0.806582 C 3.776818 1.129802 1.468718 C 3.730144-0.221089 0.758603 C -0.421752 0.547822-1.975692 0.716467 1.052155-2.555604 C 1.266960 2.049731-1.786186 C -2.602523 0.020222 0.572605 C -3.173413-0.079985 1.847925 C -4.467663-0.557213 2.025387 C -5.226289-0.934948 0.918982 C -4.673963-0.831313-0.353660 C -3.372316-0.361901-0.527835-0.994248-0.377020-2.472451 2.179634 2.705772-2.195885 H -2.949503-0.320098-1.523986 H -5.253655-1.123637-1.223871 H -6.238029-1.305778 1.049765 H -4.885817-0.628374 3.024743 H -2.590998 0.217405 2.717503 H -1.101760 1.245456 1.327411 H 0.821986 1.899182 1.629665 H 3.157262 2.286766-0.198460 H 2.760499 3.045175 1.323742 H 4.780516 1.561851 1.408269
H 3.551470 0.995251 2.535501 H 3.863788-0.074725-0.321268 H 4.534747-0.879236 1.100172 H 2.389621-1.135137 2.118289 H 0.373528 3.196386-0.247110 H -1.575879 2.059867-1.026256 H 0.412885-3.934312 0.567704 H 0.836554-3.027115 2.019959 H -1.269976-2.135733 1.327614 H -0.848464-2.138922-0.368955 Figure 20. T_6_top_exo Electronic Energy = - 1397.709280 a.u. (DE e = 10.04 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.397353 a.u. (DG = 25.60 kcal.mol -1 ) Number of imaginary frequencies: 1 (-499.6291) C 2.508646-2.271991-0.578896 C 2.886729-1.608679-1.747451 C 2.640603-2.194176-3.015464 C 2.025394-3.438233-3.136393 C 0.052225-2.952862-2.175693 C 0.273746-2.355330-0.939851 C -0.000916-3.374621 0.094832-0.228277-4.587164-0.552054 C -0.356069-4.349459-1.908371-0.735329-5.204721-2.661073-0.042052-3.289106 1.287826 H 0.169341-1.307610-0.701651 H -0.282424-2.458447-3.075968 H 2.491475-3.357846-0.624322 H 2.179358-4.161935-2.340533 C 1.656479-4.040893-4.464679 C 1.425591-2.976547-5.531446 C 2.624275-2.035878-5.576478 C 2.814382-1.311793-4.239190 4.477589-0.526356-4.306813 C 4.740433-0.121356-2.547817 C 3.454346-0.208089-1.724517 C 2.647842-1.758562 0.799167 C 2.206012-0.485907 1.185198 C 2.329129-0.058317 2.502163 C 2.891488-0.898743 3.461044 C 3.315094-2.173805 3.095943 C 3.183698-2.601981 1.779242 H 2.476682-4.703479-4.775762 H 1.275739-3.447856-6.507154 H 0.509020-2.413235-5.310839
H 3.525519-2.620071-5.799223 H 2.519046-1.292077-6.372410 H 2.077110-0.499758-4.179942 H 3.495610-3.606720 1.507697 H 3.734042-2.843538 3.839975 H 2.983656-0.566720 4.490155 H 1.972366 0.927616 2.782937 H 1.736953 0.169208 0.456564 H 0.779795-4.683735-4.342203 H 5.483950-0.807736-2.134196 H 5.145065 0.892152-2.500184 H 2.726227 0.521344-2.106155 H 3.695101 0.086493-0.702298 Figure 21. cycloadduct_6_top_exo Electronic Energy = - 1397.791275 a.u. (DE e = -41.41 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.473763 a.u. (DG r = -22.34 kcal.mol -1 ) Number of imaginary frequencies: 0 C -0.249468 1.543869 2.695400 C 0.490563 0.430343 2.285668 C 1.459055-0.077826 3.150358 C 1.689577 0.510735 4.392215 C 0.948152 1.619967 4.788088 C -0.025035 2.135808 3.933863 C 0.270641-0.207817 0.925560 C 0.758743 0.617796-0.267793 C 0.450630 0.174247-1.500710 C 0.819841 0.943990-2.761225 2.463288 1.724453-2.631813 C 2.052431 2.673875-1.143529 C 0.727741 0.135824-4.052924 C -0.616487-0.580733-4.106226 C -0.662061-1.645230-3.016469 C -0.371759-1.112627-1.597903 C -1.635340-0.878352-0.724552 C -1.217320-0.605804 0.724529 C -1.549766-1.904520 1.441215-2.357396-2.681328 0.634254 C -2.521808-2.102511-0.605552-3.274662-2.570491-1.408768-1.211812-2.280798 2.522338 H 0.200971-1.898160-1.082233 H 0.098717-2.396921-3.256666 H -0.764601-1.053023-5.082266 H -1.431328 0.145704-3.980397 H 1.538501-0.602723-4.101549 H 0.854731 0.815666-4.900863
H 0.101877 1.770718-2.863694 H 0.851041-1.141537 0.922492 H 2.031742-0.952968 2.855540 H 2.443912 0.095617 5.053158 H 1.122483 2.077915 5.756416 H -0.609204 3.000808 4.232325 H -1.001474 1.970582 2.035111 H -1.861751 0.161504 1.164523 H -2.226539-0.072901-1.167373 H -1.622055-2.166266-3.027866 H 2.926080 3.278847-0.889618 H 1.238262 3.362962-1.393641 C 1.667083 1.788073 0.035486 H 1.211759 2.425635 0.799851 H 2.573248 1.379356 0.503580 Figure 22. T_6_below_exo Electronic Energy = - 1397.711260 a.u. (DE e = 8.80 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.398672 a.u. (DG = 24.78 kcal.mol -1 ) Number of imaginary frequencies: 1 (-501.6620) C 2.650348-2.018046 0.463314 C 3.132138-2.351628 1.727739 C 2.351718-2.101874 2.885787 C 1.101054-1.493682 2.815654 C 1.731069 0.462037 1.933415 C 2.466150 0.227221 0.776831 C 1.572526 0.483669-0.372728 0.298104 0.738029 0.127715 C 0.381391 0.887049 1.500563-0.548981 1.292205 2.142343 1.791304 0.493703-1.549709 H 3.533107 0.338124 0.660638 H 2.131900 0.791099 2.881467 H 1.570816-2.045447 0.337240 H 0.508085-1.654703 1.919490 C 0.305482-1.136094 4.042326 C 1.200709-0.863428 5.246434 C 2.162459-2.030113 5.443018 C 3.047474-2.276806 4.217160 4.531948-1.168871 4.292398 C 5.344082-1.659208 2.722026 C 4.566050-2.752126 1.970737 C 3.375260-2.157799-0.818044 C 4.661345-1.644547-1.031332 C 5.286793-1.779440-2.265369 C 4.635772-2.426413-3.313652 C 3.349833-2.924588-3.122206 C 2.723312-2.780043-1.888982
H 5.172228-1.108791-0.236597 H 6.278860-1.364557-2.412968 H 5.122516-2.527406-4.278284 H 2.827482-3.413073-3.938440 H 1.712220-3.153432-1.752133 H -0.336314-0.278137 3.822474 H -0.371973-1.973711 4.263885 H 1.761997 0.066342 5.095151 H 0.591289-0.721157 6.143507 H 2.792132-1.886913 6.326602 H 1.578444-2.942349 5.619977 H 3.431776-3.298418 4.285927 H 5.434419-0.766193 2.096819 H 6.351166-2.013928 2.953130 H 4.592890-3.676072 2.558950 H 5.078563-2.975569 1.034479 Figure 23. cycloadduct_6_below_exo Electronic Energy = - 1397.796234 a.u. (DE e = -44.53 kcal.mol -1 ) um of electronic and thermal free energies = - 1397.478573 a.u. (DG r = -25.36 kcal.mol -1 ) Number of imaginary frequencies: 0 C -1.430306 1.101350 0.487404 C -1.452179-0.114372 1.444137 C -0.878422 0.683344-0.878380 C -0.055197-0.634770-0.913925 C 0.655726-0.881308 0.417897 C -0.014683-0.610861 1.548472 C 2.019533-1.529844 0.375393 C 2.406133-2.199016 1.685045 2.308690-1.034505 3.070111 C 0.525796-0.673303 2.960183 C -2.123091 0.600439-1.746706-3.172542 1.233486-1.109064 C -2.816658 1.617121 0.166839 C -2.084057 0.158128 2.811514 C -1.219963 1.062717 3.696510 C 0.278181 0.682088 3.649668-3.562923 2.249104 0.855273-2.267806 0.089584-2.816008 C 0.864635-0.653506-2.122070 C 0.718327-1.623587-3.112205 C 1.569369-1.650074-4.215695 C 2.578797-0.700533-4.342808 C 2.730832 0.278039-3.361249 C 1.878790 0.299239-2.262237
H 2.015672 1.059930-1.496062 H 3.514119 1.024270-3.450924 H 3.241789-0.718227-5.201988 H 1.437076-2.410161-4.979225 H -0.077993-2.357648-3.028709 H -0.773399-1.456705-1.046298 H -2.051318-0.897292 0.952778 H -3.077662 0.596138 2.686708 H -2.232119-0.808262 3.306678 H -1.345903 2.105190 3.386100 H -1.596385 1.006609 4.722176 H 0.850037 1.435815 3.097204 H 0.698371 0.652732 4.660010 H -0.003276-1.457625 3.517423 H -0.860806 1.909366 0.952821 H -0.270648 1.492292-1.297577 H 3.438110-2.556004 1.649003 H 1.760870-3.059878 1.890218 H 2.020043-2.282491-0.423476 H 2.785892-0.798640 0.095359
2.4. Computed conformations for 10fA-major, 10fB-minor Figure 24. Computed conformation for 10fA-major (two views)
Figure 25. Computed conformation for 10fB-minor (two views)
30
1 H and 13 C NMR spectra s 31
Ac Br 1 s 32
Ac Br 1 s 33
Br 2a s 34
Br 2a s 35
Br 2b s 36
Br 2b s 37
Br H 2c s 38
2c s 39
Br 2d s 40
Br 2d s 41
Br 2e s 42
Br 2e s 43
Br 2f s 44
Br 2f s 45
3a s 46
3a s 47
3b s 48
3b s 49
3c s 50
3c s 51
3d s 52
3d s 53
DMF 3e (impure, used directly in cycloaddi=on) CH 2 Cl 2 s 54
3f s 55
3f s 56
4aA + minor Ra=o 10/3 s 57
+ minor 4aA Ra=o 10/3 s 58
5aA N s 59
5aA N s 60
6aA C 2 Me C 2 Me 6aB C 2 Me C 2 Me Ra=o 10/3 s 61
6aA C 2 Me C 2 Me 6aB C 2 Me C 2 Me Ra=o 10/3 s 62
N 7aA Et N N Ph s 63
N 7aA Et N N Ph s 64
8a N Et N N Ph s 65
8a N Et N N Ph s 66
? 9a Me N 10a Me N Mixture of 2 products in 3/1 ra=o s 67
? 9a Me N 10a Me N Mixture of 2 products in 3/1 ra=o s 68
4bA s 69
4bA s 70
5bA N s 71
5bA N s 72
7bA N N N s 73
7bA N N N s 74
8b N N N s 75
8b N N N s 76
+ minor N 10b (major) Ra=o 10/1 s 77
10b (major) N + minor Ra=o 10/1 s 78
4 ca C 2 H s 79
4 ca C 2 H s 80
4dA s 81
4dA s 82
Me Me 6dA C 2 Me C 2 Me 6dB ra=o 2/1 C 2 Me C 2 Me Ra=o 2/10 s 83
Me Me 6dA C 2 Me C 2 Me 6dB ra=o 2/1 C 2 Me C 2 Me Ra=o 2/10 s 84
7dA Me N N N Ph + minor Ra=o 20/1 s 85
7dA Me N N N Ph + minor Ra=o 20/1 s 86
7eA N N N s 87
N N N 7eA s 88
Ph 4fA s 89
Ph 4fA s 90
Ph 7fA N N N Ph s 91
Ph 7fA N N N Ph s 92
Ph Ph 2-Py 10fA (Major) Me Ra=o 10/3 2-Py 10fA (minor) Me s 93
Ph Ph 2-Py 10fA (Major) Me Ra=o 10/3 2-Py 10fA (minor) Me s 94