henium-catalyzed Synthesis of Multisubstituted Aromatic Compounds via C-C Single-Bond Cleavage Kuninobu, Y.; Takata,.; Kawata, A.; Takai, K. rg. Lett. ASAP Et 5 6 cat. [ebr(c) 3 (thf)] 2 5 6 Current Literature Kalyani Patil 6/28/08 Kalyani Patil @ Wipf Group Page 1 of 13 7/3/2008
utline Synthesis of Substituted Aromatic Compounds henium Catalyzed eactions henium Catalyzed C- Activation - Takai Group Title Paper Summary Kalyani Patil @ Wipf Group Page 2 of 13 7/3/2008
Synthesis of Substituted Aromatic Compounds Bergman cyclization 150-200 C benzene cyclohexadiene Bergman et. al. J. Am. Chem. Soc. 1972, 94, 660 Trimerization of acetylenes (C 2 )n CpCo(C) 2 30-95% C 2 Vollhardt Angew. Chem. Int. Ed. 1984, 23, 539 ML x ML x-1 ML x-2 ML x-2 1 2 3 xidative coupling to give metallacyclopentadiene Alkyne insertion or Diels-Alder type addition 5 ML x-2 4 ML x-2 6 ML x-2 Kalyani Patil @ Wipf Group Page 3 of 13 7/3/2008
Synthesis of Substituted Aromatic Compounds ing-closing metathesis n-pr n-pr Grubbs' II C 2 Cl 2, rt, 2h n-pr n-pr n-pr n-pr Imamoto et. al. J. Am. Chem. Soc. 2005, 127, 10470 Annulation of vinylketenes with acetylenes C 3 benzene, 80 C, 26h 3 C 4 e - electrocyclic cleavage 6 e - electrocyclic closure Danheiser et. al. J.rg. Chem. 1984, 49, 1672 [22] 3 C 4 e - electrocyclic cleavage 3 C Kalyani Patil @ Wipf Group Page 4 of 13 7/3/2008
Properties of henium Grayish white metal, last naturally occurring element to be discovered Discovered in 1925 by Dr. Walter Noddack and Dr. Ida Tacke Noddack Electronic configuration: [Xe] 4f14 5d5 6s2 xidation states: -3, -1, 0, 1 to 7 Lower electronegativity than u and h Kalyani Patil @ Wipf Group Page 5 of 13 7/3/2008
henium Catalyzed eactions Friedel-Crafts alkylation ebr(c) t-bucl 5 (1 mol%) ClC 2 C 2 Cl, 84 C t-bu 93% C 3 C 3 Sonoda et. al. Bull. Chem. Soc. Jpn. 2000, 73, 2779 Anti-Markovnikov addition of carboxylic acids to terminal alkynes C ebr(c) 5 (1 mol%) toluene, 110 C 67% 13:87 ua et. al. J. rg. Chem. 2004, 69, 5782 Coupling of epoxides with C 2 C 2 ebr(c) 5 (0.1 mol%) 110 C, 85% ua et. al. J. rg. Chem. 2005, 70, 381 Kalyani Patil @ Wipf Group Page 6 of 13 7/3/2008
henium Catalyzed eactions - Toste Group Etherification of propargylic alcohols n-bu 1 mol% (dppm)ecl 3 Cl MeCN, 65 C 78% Cl n-bu Toste et. al. J. Am. Chem. Soc. 2003, 125, 6076 X [M] -X [M] [3,3] [] [M] 1 2 3 2 Synthesis of 1,5-Enynes TMS 5 mol% (dppm)ecl 3 cat. N 4 PF 6 MeN 2, 65 C 79% Toste et. al. J. Am. Chem. Soc. 2003, 125, 15760 Kalyani Patil @ Wipf Group Page 7 of 13 7/3/2008
henium Catalyzed ing Expansion - Takai Group Construction of medium size rings Insertion of terminal alkynes into C-C next to the carbonyl group n Et [ebr(c) 3 (thf)] 2 (2.5 mol%) C 2 NC (5 mol%) Et neat, 24h Et 87% 78% 78% 61% n (4-b) Et Et Et (4-a) e (I) (3-b) Et henacyclopentene intermediate Et (2-b) e Et (2-a) etro-aldol reaction/isomerization eductive elimination e (3-a) e Et Et Takai et. al. J. Am. Chem. Soc.2006, 128, 12376 Kalyani Patil @ Wipf Group Page 8 of 13 7/3/2008
henium Catalyzed C- Activation - Takai Group Formation of indene derivatives N t-bu Me cat. [ebr(c) 3(thf)] 2 toluene, reflux, 24h 95% N t-bu Takai et. al. J. Am. Chem. Soc. 2005, 127, 13498 C 2 Et cat. [ebr(c) 3 (thf)] 2 p-anisidine (15 mol%) toluene, 180 C, 24h 93% C 2 Et Takai et. al. Angew. Chem. Int. Ed. 2006, 45, 2766 Synthesis of isobenzofuran N cat. [ebr(c) 3 (thf)] 2 MS 4Å toluene, reflux, 24h 93% Takai et. al.j. Am. Chem. Soc. 2006, 128, 12376 Kalyani Patil @ Wipf Group Page 9 of 13 7/3/2008
Title Paper Et [ebr(c) 3 (thf)] 2 (2.5 mol%) MS 4Å (200 wt%-e cat.) toluene, 180 C, 24h 5 6 toluene, 150 C, 24h 5 6 Entry 5 6 Yield (%) 1. Me Me C 2 Et C 2 Et 83 2. Me C 2 Et C 2 Et 64 3. Me C 2 Et C 2 Et 84 4. Me Me Me C 2 Et C 2 Et 91 5. Me Me C 2 Et C 2 Et 87 6. Me Me n-c 10 21 C 2 Et C 2 Et 72 7. Me n-c 5 11 n-c 6 13 C 2 Et C 2 Et 85, A:B = 96:4 8. n-c 5 11 Me n-c 6 13 C 2 Et C 2 Et 83, A:B = 6:94 9. Me Me C 2 Et 83 10. Me C 2 Et 77, C:D = 39:61 Et 2 C C 2 Et n-c 5 11 Et 2 C C 2 Et C 2 Et Et 2 C n-c 5 11 n-c 6 13 n-c 6 13 A B C D Kuninobu, Y.; Takata,.; Kawata, A.; Takai, K. rg. Lett. ASAP Kalyani Patil @ Wipf Group Page 10 of 13 7/3/2008
DA w/ Benzyne Title Paper [ebr(c) 3 (thf)] 2 (2.5 mol%) MS 4Å (200 wt%-e cat) Et 1 eq. toluene, 180 C 1 (1eq.) Benzyne generated in situ to synthesize naphthalene derivatives SiMe 3, CsF(3 eq.) Tf (1.5 eq.) toluene/c 3 CN, 20 C, 12h 2 time (h) yield (%) Me (1a) 24 92 (2a) (1b) 48 96 (2b) Intramolecular eaction Et [ebr(c) 3 (thf)] 2 (2.5 mol%) MS 4Å (100 wt%-e cat) toluene, 150 C, 24h Synthesis of tetrahydronaphthalene derivatives Me 2 C C 2 Me (4 eq.) Me 2 C C 2 Me (84%) toluene, 150 C, 48h Kuninobu, Y.; Takata,.; Kawata, A.; Takai, K. rg. Lett. ASAP Kalyani Patil @ Wipf Group Page 11 of 13 7/3/2008
Title Paper: Proposed Mechanism Et Et 5 6 (5) 5 6 (6) -C 2 5 6 e (I) (1) henacyclopentene intermediate etro-aldol reaction/reductive elimination (4) -Et C 2 Et Et (3-b) 2 (2-b) (3-a) C 2 Et e (2-a) e C 2 Et Isomerization of the alkene/cyclization DA reaction/decarboxylation Kuninobu, Y.; Takata,.; Kawata, A.; Takai, K. rg. Lett. ASAP Kalyani Patil @ Wipf Group Page 12 of 13 7/3/2008
Summary Synthesis of Multisubstituted Aromatic Compounds in Good Yields Products are btained in igh egioselectivity Aliphatic and Aromatic Acetylenes employed Prior to DA eaction Kalyani Patil @ Wipf Group Page 13 of 13 7/3/2008