用于化学转化的羰基β-碳的活化的制作方法_4

9.127.3.127.1， 126.9,125.9,123.8,60.4,47.7,42.4;HRMS(ESI)calcd for C23Hi9N〇2Na(M+Na)+: 364.1313，Found:364.1318;96:4 e.r.由HPLC(Chiralcel ΙΑ，99·9:0· I己烷/i-PrOH， 0 · 3mljmin)测定，tr(major) = 63 · 8min，tr(minor) = 56 · 3min〇
实施例28:2-(11?，21〇2,4-二苯基环戊-3-烯-1-基)噻吩 ：[&]#3(〇 2.56 ,CH2CI2 )=-70.8。；94:6 e.r.由HPLC( Chiral cel ΙΑ，99·8:0· 2己烷/i-PrOH， 0 · 3mljmin)测定，tr(major) = 29 .Omin，tr(minor) = 25 · 5min〇
实施例29:2-(3R，4R)-3，4-二苯基环戊-I-烯-I-基)呋喃：[a] D23 (c 1.66，CH2Cl2)=_127.4%94:6 e.r.由HPLC(Chiralcel 0D，99.8:0.2己烷/i-PrOH， 0 · 3mL/min)测定，tr(major) = 34.4min，tr(minor) =49 · 9min〇
实施例30:((11?，21〇-4-(对甲苯基）环戊-3-烯-1，2-二基）二 苯：无色胶；[a]D23(c 1.00，CH2Cl2)=-112.4VH N R(400MHz，CDCI3)S = 2.37(s，3H)， 2.96-3.02(m,lH),3.29-3.46(m,2H),4.10-4.13(m,lH),6.20(t,J=1.6Hz,1H),7.13-7.31 (m，12H)，7.42-7.49(m，2H);13C NMR(K)OMHz，αΧΠ3)δ = 145·6,145.1,142.1,137.4,133.2， 129.2,128.5,128.4,127.5,127.3,127.I,126.4,126.3,125.7,60.8,54.5,42.0,21.3; HRMS(ESI)calcd for C24H23(M+H)+:311.1800，Found:311.1804;95:5 e.r.由HPLC (Chiralcel IA，99 · 8:0 · 2己烧/i-Pr0H，0 · 3mL min)测定，tr(major) = 26 · Imin，tr(minor) = 24.2min〇
实施例31: ((IR，2R)-4-(4-氯苯基)环戊-3-稀-I，2-二基）二 苯:无色胶；[a]D23(c 2.14，CH2Cl2)=-89.5° !1H Mffi(400MHz，CDCI3)S = 2.94-3.01(m，lH)， 3.26-3.34(m，lH),3.42-3.48(m，lH)，4·11-4.14(m，lH)，6·24(dd，J=3.6,2.OHz，1H)， 7 · 12-7 · 34(m，12H)，7 · 43-7 · 46(m，2H); 13C 匪R( 100MHz ,CDCI3) δ = 145 · I，144 · 6，141 · I， 134.5,133.2,128.9,128.6,128.5,128.5,127.4,127.3,127.I,126.5,126.4,60.8,54.5， 42.0;HRMS(ESI)calcd for C23H2〇CI(M+H)+:331.1254，Found:331.1277;95:5 e.r.由HPLC (Chiralcel IA，99 · 8:0 · 2己烧/i-Pr0H，0 · 3mL/min)测定，tr(major) = 31 · 4min，tr(minor) = 29.3min〇
实施例32: ((1R，2R)-4-(4-溴苯基)环戊-3-烯-I，2-二基)二苯：
[&]〇23(〇2.78,012(：12) = -87.5。；96:4 6义.（11?，21〇-异构体由册1^：(〇11抑1。611八，99.9: 0 · 1己烧/i-Pr0H，0 · 3mL/min)测定，tr(major) = 35 · 2min，tr(minor) = 32 · 4min〇
实施例33:4,4'-((11?，51〇-5-苯基环戊-3-烯-1，3-二基)双 (氯苯）：[a]D23(c 2.5，CH2Cl2)=-94.4°;95:5 e.r.异构体由HPLC(Chiralcel ΙΑ,99.8:0.2 己烧/i_Pr0H，0 · 3mL/min)测定，tr(major) = 49 · 5min，tr(minor) = 38 · lmin。
实施例34:4，4' -((1R，5R)-5-苯基环戊-3-烯-I，3-二基） 双（溴苯）：无色胶；[a]D23(c 3.45，CH2Cl2)=-68.8° !1H Mffi(400MHz，CDCI3)S = 2.89-2.96 (m，iH)，3.25-3.27(m，lH),3.30-3.43(m，lH),4.03-4.05(m，lH)，6.23(d，J=I·6Ηζ，1Η)， 7.08-7.49(m，13H); 13C NMR(100MHz，CDCI3)6=144.2,144.0，141.1,134.7，131.7,131.6， 130.7,129.1,128.9,128.6,127.4,126.7,121.5,120.1,60.9,54.1，41.8;HRMS(ESI)calcd for C23Hi9Br2(M+H)+:452.9854，Found:452.9868;95:5 e.r.由HPLC(Chiralcel IA，99.8: 0·2 hexanes/i_Pr0H，0·3mL min)测定，tr(major) = 59·2min，tr(minor) = 46·3min。
:实施例35:1-( (lR，2R)-4-(4-氯苯基)-2-(4-甲氧基苯基)环 戊-3-烯-1-基）萘：[a]D23(c 3.0，CH2Cl2)=-124.4°;97:3 e.r.由HPLC(Chiralcel 0D，98:2 己烧/i_Pr0H，0 · 3mL/min)测定，tr(major) = 59 · 8min，tr(minor) = 38.4min〇
[0207]注意:对于以下表征的产物，两种非对映体(例如5a和5a'）作为混合物被分离。
实施例36:4,5-二苯基-5-(三氟甲基）二氢呋喃-2(3!1)- 酮：91:9 e.r.(5a)，94:6 e.r.(5a'）由HPLC(Chiralcel 0D，99:1 己烷/i-Pr0H，0.7mL/min) 测定，tr(5a_ma jor) = 23 · Imin，tr(5a_minor) =44 · Omin，tr(5a ' _ma jor) = 19 · 8min，tr (5a'_minor) =71 · 3min〇
实施例37:4-苯基-5-(对甲苯基)-5-(三氟甲基)二 氢呋喃-2(3H)_ 酮：93:7 e.r.(5b), 95:5 e.r.(5b'）由HPLC(Chiralcel 0D, 99.8:0.2己烷 / i-PrOH, 0.7mL min)iIlJ/E , tr(5b-ma jor) = 30.5min, tr(5b-minor) = 81.3min, tr(5b '-major) =34.5min, tr(5b '-minor) = 106 · 5min〇
实施例38:5-(4-氯苯基)-4-苯基-5-(三氟甲基）二 氢呋喃-2(3!1)-酮：94:6 6义.（5。），94:6 6义.（5。'）由册1^：(〇11抑1。611厶，99:1己烷八-PrOH, 0 · 7mL/min)测定,tr(5c-major) = 18.2min, tr(5c-minor) = 38.5min, tr( 5c '-major) =19 · 4min, tr(5c '-minor) = 69 · 2min〇
实施例39:5-(4-溴苯基)-4-苯基-5-(三氟甲基)二 氢呋喃-2(3H)_酮：无色油，1H NMR(400MHz,ΟΧΠ 3)δ = 2.74-2.81(trans，m，lH)，2.95-2.97 (c/s，m，lH)，3.17-3·32(c/s，m，1H)，3·34-3·39(trans，m，lH),3.93(cis，t，J = 9.6Hz，1H)， 4.26(trans ,dd, J = 9.6,5.2Hz , 1H),6.84-6.87(trans ,m,2H),7.01 (frans ,d, J = 8.4Hz , 2H),7.13-7.16(trans,m,3H),7.27-7.33(frans+cis,m,4H),7.39-7.42(cis,m,5H),7.56-7.58(c/，s，m，2H); 13C NMR(100MHz，CDCI3)S = 173.4(trans)，172.7(cis)，137.4(frans), 134.5,133.2,132.0,131.1,130.5,129.3，129·0，128·9，128·9,128.8,128.7,128.3， 128.1,127.3,127.3,125.7,124.1,123.4,122.9,88.2(q,J = 290Hz) (frans) ,87.3(q J = 260Hz)(c//s),51.6(c/s),45.7(trans),36.8(trans),35.l(c/s)；HRMS(ESI)calcd for Ci7Hi3〇2F3Br(M+H) + : 385.0051，Found:385.0055;93:7 e.r.(5d),94:6 e.r.(5cT )由HPLC (Chiralcel IB，98: 2己烧/i-PrOH，0 · 5mL/min)测定，tr (5d_ma jor) = 22.1min，tr(5d-minor) =44.7min，tr(5d'-major) = 24 · 3min，tr(5d '-minor) = 74.6min 〇
实施例40:4-苯基-5-(噻吩-2-基)-5-(三氟甲基）二氢 呋喃-2(3H)_酮：90: lOe.r. (5e)，91:9 e.r. (5e，）由HPLC(Chiralcel OD，99:1己烷/i-PrOH,0.7mL/min)测定,tr(5e-major) =41.6min, tr(5e-minor) = 70.5min, tr(5e '-major) = 26.611^11,1:3:(56^111:111010 = 87. Imin0
实施例41:5-苯基-4-(对甲苯基)-5-(三氟甲基)二氢呋喃- 2(3H)_酮：无色油；1H NMR(400MHz，CDCI3)S = 2.21(trans，s，3H)，2.39(cis，s，3H)，2.7卜 2.77(frans,m,H) ,2.90(cis,q,J = 8.8Hz,H) ,3.14(cis,dd,J = 18.0,10.0Hz,lH) ,3.26-3.33( trans ,m, lH),3.97(cis,t,J = 5.2Hz , 1H) ,4.25(trans ,dd, J = 9.2,5.6Hz , 1H) ,6.71 (trans, d ,J = 8. OHz , 2H), 6'91 (trans , d ,J = 8. OHz . 2H), 7.12-7.22(trans+cis ,m, I OH), 7.44(trans，dd，J = 6.4,3.6Hz，2H)，7.53-7.54(cis，m，2H) ;13C 匪R(100MHz，CDCI3)S = 173.Q(trans),173.4(c/s),138.6(0/7 s),37.6(irans),135.6(c/7 s),134.4(irans), 131.3(irans),130.7(0/7 s),129.5,129.4,129.2,128.8,128.7,128.3,127.8,127.0, 126.9.126.0. 125.6.125.3.123.2.122.5.88.5(q, J = 280Hz)(trans)，87.4(q，J = 280Hz) (cis),51.2(c/s),45.5(frans),36.8(trans),35.3(c/'s),21.l(c/s),2*\.0(trans)； HRMS(ESI)calcd for Ci8Hi6〇2F3(M+H)+:321.1 102,Found:321.1101；92:8 e.r.(5f),95:5 e · r · (5f'）由HPLC(Chiralcel OD，95 : 5己烧/i-PrOH, 0 · 7mL/min)测定，tr(5f-ma jor)= 19 · 5min, tr(5f-minor) = 34 · 7min，tr(5f-major) = 14.8min，tr(5f-minor) =40 · 3min〇
实施例42:4-(4-氟苯基)-5-苯基-5-(三氟甲基)二氢呋喃-2 (3H)-酮：colorless Oil51H NMR(400MHz，CDCI3)S = 2.70-2.76(m，lH) ,3.29-3·37(ι?，1H)， 4.28(dd ,J = 9.6,5.6Hz,lH) ,4.03-4.05(m, 1H) ,6.80(d ,J = 6.8Hz ,4H) ,7.11-7.22(m, 5H) ;13C 匪R(100MHz,CDCI3)δ = 173.5,163.3,160.8,133.4,133.3,131.1,130.1,130.0, 129.0. 128.0.126.8.115.6.115.4.88.4(q，J=290Hz)，45.2,36.8;HRMS(ESI)calcd for Ci7Hi3〇2F4(M+H)+:325.0852，Found:325.0852;95:5 e.r.(5g),92:8 e.r.(5g，）由HPLC (Chiralcel OD，99 :1己烧/i-PrOH，0 · 7mL/min)测定，tr(5g_ma jor) = 28 · 5min，tr(5g-minor) =26· Imin，tr(5g'-major) = 23 · Imin，tr(5g'-minor) = 39·8min〇
实施例43:4-(4-溴苯基)-5-苯基-5-(三氟甲基)二氢呋喃-2 (3H)-酮：无色油；1H NMR(400MHz，CDCI3)S = 2.67-2.74(trans，m，lH)，2.93-2.96(c/'s，m， 1H) ,3.06-3.09(0/7 s,m,lH) ,3.29-3.67( trans,m,lH), 3.97(c/s,tJ = 9.2Hz,lH) ,4.25 (trans,dd,J-9.6,5.2Hz, IH),6.71(trans,d,J = 8.8Hz,2H),7.12-7.26(trans+cis,m, 10H)，7 · 44-7 · 46( trans，m, 2H)，7 · 50-7 · 56(c/s，m, 4H); 13C NMR( IOOMHz，CDCI3)6= 173 · 3 (irans),172.8(c/s),36.7(trans),135.2(0/7 s),133.0,132.0,131.7,131.0,130.9, 130.0,129.7,129.2,128.9,128.1,126.8,126.8,125.9,125.5,123.0,122.9,121.9,88.9 (q,J = 280Hz)(trans) ,87.6(q, J = 280Hz) (c/7 s),51.0(cis) ,45.4(/rans) ,36.7(irans), 35.1(c/'s);HRMS(ESI)calcd for Ci7Hi2〇2F3Br a(M+a)+:406.9870，Found:406.9860;94:6 e.r. (5h)，96:4 e.r. (5h，）由HPLC(Chiralcel 0D，99:1 己烷/i-Pr0H，0.7mL/min)测定，tr (5h-ma jor) = 52 · 9min，tr(5h-minor) = 114 · 9min，tr(5h ' -ma jor) =41 · 4min，tr( 5h ' -minor) =30 · 2min〇
实施例44 :4-(呋喃-2-基）-5-苯基-5-(三氟甲基）二氢呋 喃-2(3H)_ 酮：84:16 e.r.(5i)，84:16 e.r.(5i'）由HPLC(Chiralcel 0J-H，95:5己烷/i-PrOH,0.5mL/min)测定,tr(5i-major) = 18.9min, tr(5i-minor) = 28.9min,tr(5i '-major) = 74. Imin，tr(5i '-minor) = 62.6min〇
实施例45: (2R，3R)_乙基I-苯甲酰氨基-5-氧代-3-苯基吡咯烷-2-羧 酸酯：无色油；[a]D23(c 0.94,CH2CI2) =-39.1° .1H NMR(400MHz，CDCI3)S0.81 (t，J = 7.2Hz， 3H)，2.92(d，J=8.8Hz，2H)，3.64-3.72(m，lH)，3.77-3.85(m，lH),4.10-4.17(m，H),4.96 (d，J = 8.8Hz，lH)，7.25-7.36(m，5H)，7.45(t，J = 8.0Hz，2H)，7.56(t，J = 7.6Hz，lH) ,7.83 (d，J = 8.0Hz，2H)，8.29(s，lH) .HRMS(ESI)Calcd for C2〇H2oN2〇4(M+H) + :353.1501 ,Found: 353.1496;97:3e.r.由HPLC[Chiralcel 1厶，75:20:5己烷/(己烷：卜卩抑!1:(：!13011=90:5:5)/ i-PrOH, 0 · 7mL/min)]测定，tr(ma jor) = 110 · 2min，tr(minor) = 88 · 3min〇
实施例46: (2R，3S)_乙基]-苯并酰胺-3-(4-氟苯基）-5-氧代吡咯 烷-2-羧酸酯:黄色油；[a]d23(c 1 · 95，CH2CI2) = -44 · 9° ;H NMR(400MHz，CDCI3)6 = 1 · 23(t，J = 7.2Hz,3H),2.63(dd ,J=17.6Hz,9.6Hz,lH),3.04(dd ,J=17.6Hz,9.6Hz,lH),3.56-3.61 (m,lH),4.17-4.29(m,2H) ,4.68(d ,J = 5.2Hz , 1H), 7.09(t, V = 8.4Hz , 2H), 7.41-7.49(m, 4H) ,7.55(t，J = 7.2Hz，lH) ,7.85(d，J = 7.2Hz，2H)，8.61(bs，lH);3C NMR(K)OMHz，ΟΧΠ3)δ =172.5,170.8,166.1,163.5,161.0,137.3(d, J = 3. OHz) ,132.7,131.2,128.9(d, J = 9.0Hz),128.7,127.5,116.0(d,J=21.0Hz),67.3,62.0,39.9,36.8,14.1；HRMS(ESI)calcd for C2〇H2oN2〇4F(M+H)+:371.1407，Found:371.1410;97:3 e.r.由HPLC[Chiralcel IA，75: 20:5己烧/ (己烧：i-PrOH: CH3OH = 90 : 5 : 5) / i-PrOH，0 · 7mL/min)]测定，tr (ma jor)= 127·3min，tr(minor) = 105·4min 〇
实施例47: (2R，3S)_乙基I-苯甲酰氨基-3-(4-氯苯基)-5-氧代吡 咯烷-2-羧酸酯：黄色油；[a]D23(c 1 ·89 ,CH2CI2) =-67 · 2° ; 1H NMR(400MHz，CDCI3)6 = 1 · 23 (t,J = 7.2Hz,3H) ,2.64(rid,J=17.6Hz,6.4Hz,lH) ,3.06(dd,J=17.6Hz,9.6Hz,lH), 3.56- 3.61(m,lH) ,4.15-4.30(m,2H) ,4.67(d ,J = 5.6Hz , 1H), 7.37-7.45(m,6H), 7.52(t J = 7.6Hz，lH)，7.84(d，J = 7.2Hz，2H)，8.83(bs，l