1、 2008 M 28 Vol. 28, 2008 4 , 605j616 Chinese Journal of Organic Chemistry No. 4, 605j616 * E-mail: or Received December 15, 2007; revised and accepted February 25, 2008. SE1 S (No. 20732006)aS So 9p “ 8 Z b XQ 9mfa,bf|*,akyb *,b (av S 325027) (bS S Z SE L i Z 200032) K1 XQ YP 3KrZEB , 7 XQ54 mY 3o
2、 . 8 M mls0b XQZ . 1oM b ; 4 ; X ; b Organocatalytic Asymmetric Friedel-Crafts Reactions SHENG, Yi-Feia,bZHANG, An-Jiang*,aZHENG Xiao-JianbYOU, Shu-Li*,b(a College of Chemistry and Material Engineering, Wenzhou University, Wenzhou 325027) (b State Key Laboratory of Organometallic Chemistry, Shanghai
3、 Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032) Abstract Friedel-Crafts alkylation is one of the most efficient methods for the derivatization of aromatic compounds. Asymmetric Friedel-Crafts alkylation reaction provides direct access to the enantiopure aro-matic deriv
4、atives. In this paper, the recent progress in organocatalytic asymmetric Friedel-Crafts reactions is reviewed. Keywords asymmetric catalysis; enantioselective; Friedel-Crafts; organocatalysis ioQ K1Q , XQ5 yYPM ioKrZEB1. 1V Friedel Crafts n XQ2, B M , XQ s T1 , 7 O$ s0 . 7 , XQ ?ZM , E M | Bt1Z3. 6B
5、Z , 1 2000 M bQ ?Z4, 7 ls0b XQ9sv ji | BtdzT . b1 mY4 drZE . M b XQY s8 8 . 1 ,- 2001 M , MacMillan lF5 b 6 3 ,- XQ . lF P m,: 15 ,- 0 27o , 7 N-J 6? 34 XQ (m 1). 606 Vol. 28, 2008 m 1 MacMillan m,: 1 Figure 1 MacMillans secondary amine catalyst 1 YVb4 I , m,: 1TFATb4 , LC N-J 6B“ ,- 1,4- XFQ (V 1).
6、 QBYPB| ,- | p q ee (V 1, Entries 1j6), 7 OBt 0 (V 1, Entry 7)91 zT . , I v | 6#Bt #W | N-J 6Q f , T1 i (74%j87% q , 89%j97% ee ). V 1 b N-J 6 ,- XQ Table 1 Organocatalyzed asymmetric Friedel-Crafts alkylation of N-methyl pyrrole with ,-unsaturated aldehydes Entry R Temp/ Time/h Yield/% ee/%1 Me 60
7、72 83 91a2 Pr 50 72 81 903 i-Pr 50 72 80 914 Ph 30 42 87 935 4-MeOC6H4 30 104 79 916 CH2OBn 60 72 90 87a7 CO2Me 50 104 72 90baUsing 10 mol% catalyst; b using catalyst 1-NCCH2CO2H. B?C , N-J 6V ?3F . N$ P ,- , V| 6 , ee r 99% (Scheme 1). Scheme 1 1 V 5000 ? c86, t 8 B 10 , 091 . 2002 M , Mac-Millan l
8、F6 m=) 3 b ,-0 ) O1 1;B 3h8s , y7 svK . 2001 M , MacMillan lF7 ,: b4 LC ) ,- 4 XQ . 5 6 )M , T |Q , 6Q1 )1 , X )QNo. 4 9mfb XQ 607 f , lF Pb4 3 LC ) XQ (Eq. 3). b4 3Q AUQ , TYV9 / d : bQ1#o % , b4 3 v |_B , V7 PQ0 0o p 6B , E l , ; M1/ , b4 1 #J0 0BET . “oV , b4 3 W8 )? 3FQ HE9 l , V7A U Mb4 1Q . YV
9、 b4# 4 I , 3-TFAKb4 , V(CH2Cl2)V(i-PrOH)“ 8515 4 . QQ cE v | H9zQ (V 2), ) 4- |QY9l . V 2 b ) ,- Q Table 2 Organocatalyzed asymmetric Friedel-Crafts alkylation of indoles with ,-unsaturated aldehydes Entry R1R2Y Z Temp/ Time/h Yield/% ee/%1 Me Me H H 87 19 82 922 Me Pr H H 60 6 80 933 Me i-Pr H H 50
10、 32 74 934 Me CH2OBz H H 83 18 84 965 Me Ph H H 55 45 84 906 Me CO2Me H H 83 21 89 917 H Me H H 60 22 72 918 Allyl Me H H 72 20 70 929 CH2Ph Me H H 60 120 80 8910 H Me H Me 60 3 94 9411 Me Me H OMe 87 19 90 9612 H Me Cl H 60 13 73 97MacMillan lF7|Q 5 (Eq. 4), A U Bt m0 - . , MacMillan lF8?C ?Z,: b4b
11、 ,- ? 3 XQ H , 0 T k49? 3 Q , m . YVb4 , ?C,: 6 TFA Kb4 , az , ( ? q (67%j97%), z Q1 (91j# 251) ee (99%j# 99%)LC1 Q (Eq. 5). H , Q 9T I (m 2). 2006 M , Bonini lF9d 3? 7 TFA Tb4 (Scheme 2), LC N- Scheme 2 608 Vol. 28, 2008 m 2 b Figure 2 Mechanism for Cascade catalysis J 6 N-J ) I XFQ , eeK Vr 75%. i
12、 , olF10 2007 M ,:Tb4 LC ) ,- s0 = X1Q , TYV F !9 ) 3 . YVb4 I , ?Cb4 3 q 4 1b4 1 L- 1 , N$ b4 3 b4 , ?C 3,5-(NO2)2C6H3CO2H Kr b4 . Q HW R , PY T 4 H , QM yi ? q4 , a9dz . H i , Y T 4 H , Q4 Y (Eq. 6). ?C , ) 5-JJ H V4 , 7 0 F, Cl, Br H , Q4 : Br# Cl# F. Q V a N,N-=J |b ) ,-bQ XQ . YVB“ b4 I , ?C m
13、; 12d ? | zT (Eq. 13). B , = oJ 4 , 24 / , 20 mol% 12dKDQHq . N$ , lF a I , ?C t q Es X (35%j88%), 610 Vol. 28, 2008 ? |4 (71%j89% ee). T ; 12d ?b ) ,-bQ XQ y ; B2 ?v , 7 ON V . ; _ n5bQb _o7 , YV ; 12d 0 ) _ _o e )bQFZ_ , V7 LC4 (Scheme 3). Scheme 3 2006 M , Connon lF18 m# ;b N-J ) ,-bQ XQ . YVb4 I
14、 , ; 13Kb4 . NQ4M , ee 12%j50% (Eq. 14). 2007 M , =lF19 m2 ?v;b 2-Mp ,-bQ XQ ,i4 Q V ? (Scheme 4). YVb4I , ?C 14a Kb4 , ? l q z4 ( q69%j83%, ee 85%j95%). 14b b 1-MpbQQ H , 9 ?1 zT ( q 67%, ee 80%) XF (Scheme 4). Scheme 4 4 a b ) Michael s8W1,4- FQ , 7ls0b ) 1,2-FQ M . 2005 M , JrgensenlF20 m 15 b )
15、- XFQ , ? l q ee (Eq. 15). 6 , ?CMb4 4 vY . No. 4 9mfb XQ 611 M , Trk PrakashlF21 ,a3b ) J XQ . YVb4 , ?Cb4 16a 16b sY 3 Kb4 . Q ) ? q z ee X (Scheme 5). Trk 9- Q4 1oT . Scheme 5 2006 M , Deng lF229 ,a 3b )B“ XQ . YVb4 I , ?C 17d bQ H ? |z q4 (Scheme 6). B?C , NQ a1 z , | ) | - V ? 3 XQ (q 52%j97%,
16、ee 81%j99%). ?CQi4Yl . , Q 6G ? 4 , y7 *tQ0 |YP - , VYV 6 , 9v iZE q4 . B4 , b4 17d9 ?rb )eYP XQ , V | z q4 ( q 60%j96%, ee 82%j93%). T , 3a 3 6-4 XFv . 5 2004 M , Terada lF23 m (R)-18 Scheme 6 T + b 2-JQ 1,2-XFQ (Eq. 16). Q B06Q , ?4B#01 1cmZE . V 1,2-= oY ?Kz4 , i O ?r44 . N-Boc YP Y |QQ q4Y l , 7
17、 Ob4 0.5 mol% H , X ) , Q9 ?z(Entry 13, V 3). 2006 M , Deng lF24 , 3a 3 22b ) XQ , q41 (Eq. 17). , b8“ aYP | , 3 | , 9 V |zT ( q53%j88%, ee 92%j97%). 612 Vol. 28, 2008 V 3 b 2-JQ N-Boc XQaTable 3 Organocatalyzed asymmetric Friedel-Crafts reactions of 2-methoxy-furan with N-Boc aldimines Entry R Yiel
18、d/% ee/% 1 p-MeOC6H495 96 2 o-MeC6H484 94 3 m-MeC6H480 94 4 p-MeC6H496 97 5 o-BrC6H485 91 6 m-BrC6H489 96 7 p-BrC6H486 96 8 p-ClC6H488 97 9 p-FC6H482 97 10 1-Naphthyl 84 86 11 2-Naphthyl 93 96 12 2-Furyl 94 86 13bPh 95 97 a Reactions were carried out with 0.1 mmol of aldimine in 1 mL of 1,2-dichloro
19、ethane at 35 for 24 h. bThe reaction was performed on a 1 g scale in the presence of 0.5 mol% of (R)-18. 2007 M , lF25 mb) XFQ (Eq. 18). YVB“ m I , ?C 19 ? |K4 , i OQ ? HW = . , 44 , Q q / . 60 H , Q V 83% l q 98% eeF . | )YP KHq/ Q , ? |1 iT (V 4). , Q l q4v/ (Entry 15, V 4). V 4 ) N- XQ Table 4 En
20、antioselective Friedel-Crafts reaction of indoles with N-sulfonyl aldimines EntryaR R R Time/min Yield/% ee/%1 H H Ts 30 83 982 H H Bs 15 88 993 5-OMe H Ts 20 87 974 5-OMe H Bs 15 84 995 5-Me H Ts 15 89 # 996 5-Me H Bs 15 83 997 5-Br H Ts 40 82 988 5-Br H Bs 40 89 # 999 6-Cl H Ts 120 68 9810 6-Cl H
21、Bs 90 87 # 9911 H 4-Me Ts 10 93 # 9912 H 3-NO2Ts 15 85 8913 H 3-OMe Ts 60 90 9614 H 3-OMe Bs 60 90 9715 H 300 56 5816bH H Bs 40 94 # 99aReaction conditions: 5 equiv. of indole, 10 mol% of 19, 60 , 0.25 mol/L of B in toluene. b2 equiv. of A and 5 mol% of 19 were used in a 10 mmol scale of B. M , Anti
22、llalF269 mb ) XFQ (Eq. 19). YVb4 I , ?C (S)-21 bQ H q , 41 (S)-20 rT . lF m (S)-20 LC B“ )bPictet-Spengler Q . Q? 3s0Wi , y7 Qrb i . 2004 M , JacobsenlF m ;b Pictet-Spengler Q . YVb4 I , ?Cb4 23 B“ V4s0 = (V 5). V 5 23b Pictet-SpenglerQ Table 5 Asymmetric acyl-Pictet-Spengler reaction catalyzed by 2
23、3 Entry R R t/ Yield/% ee/%1 H CH(CH2CH3)2 30 65a932 H CH(CH3)2 40 67b853 H n-C5H11 60 65b954 H CH2CH(CH3)2 60 75b935 H CH2CH2OTBDPS 60 77b906 5-MeO CH(CH2CH3)2 40 81a937 6-MeO CH(CH2CH3)2 50 76b86aPerformed with 5 mol% catalyst; bperformed with 10 mol% catalyst. 2007 M , JacobsenlF m ; 24b Pictet-S
24、pengler Q , ? z q4 (Eq. 22). 614 Vol. 28, 2008 2006 M , List lF mbPictet-Spengler Q . ?C (S)-25 Krb4 , ? q4 (Eq. 23). - )Y 3d Q ? q (94%j98%)4 (86%j90%). a9dz , ? |pT( q 50%j98%, ee 72%j94%). JacobsenlF29TM1 , mbQ8“ aS , YP 9 ? |zT , +Y Bt 0YP , K V 98% q 96%ee . 2007 M , HiemstralF329 mb Pictet-Spe
25、nglerQ , |T9Mp . 6 M , YV 0o LC XQ , 70o LC XQn . 2006 M , TeradalF33 m (R)-25 b ) XQ (Eq. 24). b/ V y M , ZE ?ZL1 1- ) -1- 3 . lFYVQHq I , ?CY 4 , 20 / , b4 (R)-25 k ) 3 | N-Boc ? |zT (q 63%j98%, ee 90%j96%). i , 2007 M lF34 mb| ) XQ . Q Vry 3- |1 m (Eq. 25). YVb4 I , ?C P (S)-25 bQ H , ? z q4 . aV , ?C YW 0 | 0 | ? |zT . Y # | H , Q4 A . H Q 9 , ?C N-J ) (26) N-J (27) ?“Hq/? 3M XQ (Scheme 7), N ) _0as 11 . Scheme 7 No. 4 9mfb XQ 615 7 ls0“ ?rb XQ , bY XQ9? |
