Recent advances in C-heteroatom bond forming by asymmetric Michael addition

Molecular Diversity

Volumn 18, Issue 2, 2014, Pages 411-439

  Heravi, Majid M ^a   Hajiabbasi, Parvin ^a  

^a ALZAHRA UNIVERSITY   (Iran)

Author keywords

Asymmetric synthesis; C heteroatom bond formation; Chiral catalyst; Chiral reagent; Enantioselectivity; Michael addition

Indexed keywords

NITROGEN; OXYGEN; PHOSPHORUS; REAGENT; SULFUR; ALKENE; CARBON;

ALKYLATION; AMINATION; ASYMMETRIC SYNTHESIS; ATOM; C HETEROATOM; CATALYST; CHEMICAL BOND; CHIRALITY; DIELS ALDER REACTION; ENANTIOSELECTIVITY; HYDROGENATION; MICHAEL ADDITION; OZONOLYSIS; PRIORITY JOURNAL; PROTON TRANSPORT; REACTION ANALYSIS; REVIEW; SUZUKI REACTION; CHEMISTRY; ENZYME SPECIFICITY; STEREOISOMERISM;

ALKENES; CARBON; NITROGEN; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

EID: 84898827675     PISSN: 13811991     EISSN: 1573501X     Source Type: Journal    
DOI: 10.1007/s11030-013-9494-2     Document Type: Review

References (89)

1. Michael A (1887) Ueber die addition von natriumacetessig- und natriummalonsäureäthern zu den aethern ungesättigter säuren. J Prakt Chem 35:349-356. doi: 10.1002/prac.18870350136
2. Michael A (1894) Ueber die Addition von natriumacetessig- und natriummalonsäureäther zu den aethern ungesättigter säuren. J Prakt Chem 49:10-20. doi: 10.1002/prac.18940490103
3. Belokon YN, Kochetkov K, Churkina ZD, Chesnokov AA, Smirnov VV, lkonnikov NS, Orlova A (1998) The first example of asymmetric Michael reaction catalyzed by chiral alkali metal alkoxides. Russ Chem Bull 47:76-83. doi: 10.1066-5285/98/4701-0074
4. Heravi MM, Hashemi E (2012) Recent applications of the Suzuki reaction in total synthesis. Tetrahedron 68:9145-9178. doi: 10.1016/j.tet.2012.08.058
5. Heravi MM, Hashemi E (2012) Recent advances in application of intramolecular Suzuki cross-coupling in cyclization and heterocyclization. Monatsh Chem 143:861-880. doi: 10.1007/s00706-012-0746-0
6. Heravi MM, Fazeli A (2010) Recent advances in the application of the Heck reaction in the synthesis of heterocyclic compounds. Heterocycles 81:1979-2026. doi: 10.3987/REV-10-675
7. Heravi MM, Sadjadi S (2009) Recent advances in the application of the Sonogashira method in the synthesis of heterocyclic compounds. Tetrahedron 65:7761-7775. doi: 10.1016/j.tet.2009.06.028
8. Heravi MM, Faghihi Z (2012) McMurry coupling of aldehydes and ketones for the formation of heterocyles via olefination. Curr Org Chem 16:2097-2123. doi:1385-2728/12
9. Heravi MM, Asadi S (2012) Recent applications of organocatalysts in asymmetric aldol reactions. Tetrahedron Asymmetry 23:1431-1465. doi: 10.1016/j.tetasy.2012.10.002
10. Heravi MM, Asadi S, Laskarani BM (2013) Recent progress in Biginelli reaction. Mol Divers 17:389-407. doi: 10.1007/s11030-013-9439-9
11. Heravi MM, Hajiabbasi P (2012) Recent advances in Kumada-Tamao-Corriu cross-coupling reaction catalyzed by different ligands. Monatsh Chem 143:1575-1592. doi: 10.1007/s00706-012-0838-x
12. Jautze S, Peters R (2010) Catalytic asymmetric Michael additions of α -cyanoacetates. Synthesis 365-388. doi: 10.1055/s-0029-1218601
13. Roca-Lopez D, Sadaba D, Delso I, Herrera RP, Tejero T, Merino P (2010) Asymmetric organocatalytic synthesis of γ -nitrocarbonyl compounds through Michael and Domino reactions. Tetrahedron Asymmetry 21:2561-2601. doi: 10.1016/j.tetasy.2010.11.001
14. Thirumalaikumar M (2011) Enantioselective Michael addition reactions. Org Prep Proced Int 43:67-129. doi: 10.1080/00304948.2011.547102
15. Zhang Y, Wang W (2012) Recent advances in organocatalytic asymmetric Michael reactions. Catal Sci Technol 2:42-53. doi: 10.1039/C1CY00334H
16. Donner CD (2013) Tandem Michael-Dieckmann/Claisen reaction of ortho-toluates - the Staunton-Weinreb annulations. Tetrahedron 69:3747-3773. doi: 10.1016/j.tet.2013.03.034
17. Johansson MH (2012) Reversible Michael additions: covalent inhibitors and prodrugs. Mini Rev Med Chem 12:1330-1344. doi: 10.2174/138955712804586693
18. Davies SG, Smith AD, Price PD (2005) The conjugate addition of enantiomerically pure lithium amides as homochiral ammonia equivalents: scope, limitations and synthetic applications. Tetrahedron Asymmetry 16:2833-2891. doi: 10.1016/j.tetasy.2005.08.006
19. Davies SG, Fletcher AM, Roberts PM, Thomson JE (2012) The conjugate addition of enantiomerically pure lithium amides as chiral ammonia equivalents part II: 2005-2011. Tetrahedron Asymmetry 23:1111-1153. doi: 10.1016/j.tetasy.2012.08.009
20. Enders D, Wang C, Liebich JX (2009) Organocatalytic asymmetric aza-Michael additions. Chem Eur J 15:11058-11076. doi: 10.1002/chem.200902236
21. Wu Y, Wang J, Li P, Kwong FY (2012) Catalyst-free efficient aza-Michael addition of azoles to nitroalkenes. Synlett 23:788-790. doi: 10.1055/s-0031-1290359
22. Nising CF, Bräse S (2012) Recent developments in the field of oxa-Michael reactions. Chem Soc Rev 41:988-999. doi: 10.1039/C1CS15167C
23. Dai L, Yang H, Niu J, Chen F (2012) Enantioselective protonation in the sulfa-Michael addition using chiral squaramides as hydrogen-bonding organocatalysts. Synlett 314-316. doi: 10.1055/s-0031-1290113
24. Herrmann WA (2002) N-heterocyclic carbenes: a new concept in organometallic catalysis. Angew Chem Int Ed 41:1290-1309. doi: 10.1002/1521-3773(20020415)
25. Hughes G, Bryce MR (2005) Electron-transporting materials for organic electroluminescent and electrophosphorescent devices. J Mater Chem 15:94-107. doi: 10.1039/B413249C
26. Holmes GA, Rice K, Snyder CR (2006) Ballistic fibers: a review of the thermal, ultraviolet and hydrolytic stability of the benzoxazole ring structure. J Mater Sci 41:4105-4116. doi: 10.1007/s10853-005-5597-1
27. Zuend SJ, Coughlin MP, Lalonde MP, Jacobsen EN (2009) Scaleable catalytic asymmetric Strecker synthesis of unnatural α -amino acids. Nature 461:968-970. doi: 10.1038/nature08484
28. Risseeuw MDP, Overhand M, Fleet GWJ, Simone MI (2007) A compendium of sugar amino acids (SAA): scaffolds, peptide- and glyco-mimetics. Tetrahedron Asymmetry 18:2001-2120. doi: 10.1016/j.tetasy.2007.08.004
29. Lykke L, Monge D, Nielsen M, Jørgensen K (2010) Asymmetric organocatalytic formal aza-Michael addition of ammonia to nitroalkenes. Chem Eur J 16:13330-13334. doi: 10.1002/chem.201002415
30. Zhou Y, Li X, Li W, Wu C, Liang X, Ye J (2010) Asymmetric organocatalytic Michael addition of α, β -unsaturated ketone with 1,2,4-triazole. Synlett 2357-2360. doi: 10.1055/s-0030-1258040
31. Maké O, Dez I, Levacher V, Briére JF (2010) Enantioselective phase-transfer catalysis: synthesis of pyrazolines. Angew Chem Int Ed 49:7072-7075. doi: 10.1002/anie.201002485
32. Lv J, Wu H, Wang Y (2010) Organocatalytic enantioselective aza-Michael additions of N -heterocycles to α, β -unsaturated enones. Eur J Org Chem 2073-2083. doi: 10.1002/ejoc.200901227
33. Fu X, Feng J, Dong Z, Lin L, Liu X, Feng X (2011) Enantioselective synthesis of 2-substituted-1,5-benzodiazepines through domino reaction of o -phenylenediamine and chalcone derivatives. Eur J Org Chem 5233-5236. doi: 10.1002/ejoc.201100938
34. Bräse S, Gil C, Knepper K, Zimmermann V (2005) Organic azides: an exploding diversity of a unique class of compounds. Angew Chem Int Ed 44:5188-5240. doi: 10.1002/anie.200400657
35. Uraguchi D, Kinoshita N, Kizu T, Ooi T (2011) Enantioselective aza-Michael addition to conjugated nitroenynes catalyzed by chiral arylaminophosphonium barfates. Synlett 1265-1267. doi: 10.1055/s-0030-1260541
36. Didier D, Meddour A, Bezzenine-Lafollée S, Collin J (2011) Samarium iodobinaphtholate: an efficient catalyst for enantioselective aza-Michael additions of O -benzylhydroxylamine to N -alkenoyloxazolidinones. Eur J Org Chem 2678-2684. doi: 10.1002/ejoc.201100041
37. Lu X, Deng L (2008) Asymmetric aza-Michael reactions of α, β -unsaturated ketones with bifunctional organic catalysts. Angew Chem Int Ed 47:7710-7713. doi: 10.1002/anie.200802785
38. Wang C, Tunge JA (2008) Asymmetric cycloadditions of palladium-polarized aza- o -xylylenes. J Am Chem Soc 130: 8118-8119. doi: 10.1021/ja801742h
39. Enders D, Wang C, Raabe G (2009) Enantioselective synthesis of 3 H -pyrrolo[1,2- a ]indole-2-carbaldehydes via an organocatalytic domino aza-Michael/aldol condensation reaction. Synthesis 4119-4124. doi: 10.1055/s-0029-1217069
40. Lin Q, Meloni D, Pan Y, Xia M, Rodgers J, Shepard S, Li M, Galya L, Metcalf B, Yue TN, Liu P (2009) Enantioselective synthesis of janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction. Org Lett 11:1999-2002. doi: 10.1021/ol900350k
41. Reboule I, Gil R, Collin J (2008) Enantioselective conjugate addition of aromatic amines to N -alkenoyloxazolidinones catalyzed by iodido(binaphtholato) samarium. Eur J Org Chem 532-539. doi: 10.1002/ejoc.200700861
42. Yanagisawa A (2004) In comprehensive asymmetric catalysis. Springer, Berlin
43. Hamashima Y, Tamura T, Suzuki S, Sodeoka M (2009) Enantioselective protonation in the aza-Michael reaction using a combination of chiral Pd- μ -hydroxo complex with an amine salt. Synlett 1631-1634. doi: 10.1055/s-0029-1217347
44. Takizawa S, Inoue N, Hirata S, Sasai H (2010) Enantioselective synthesis of isoindolines: an organocatalyzed domino process based on the aza-Morita-Baylis-Hillman reaction. Angew Chem Int Ed 49:9725-9729. doi: 10.1002/anie.201004547
45. Lu M, Zhu D, Lu Y, Hou Y, Tan B, Zhong G (2008) Organocatalytic asymmetric a-aminoxylation/aza-Michael reactions for the synthesis of functionalized tetrahydro-1,2-oxazines. Angew Chem Int Ed 47:10187-10191. doi: 10.1002/anie.200803731
46. Bandini M, Bottoni A, Eichholzer A, Miscione GP, Stenta M (2010) Asymmetric phase-transfer-catalyzed intramolecular N -alkylation of indoles and pyrroles: a combined experimental and theoretical investigation. Chem Eur J 16:12462-12473. doi: 10.1002/chem.201000560
47. Cai Q, Zheng C, You SL (2010) Enantioselective intramolecular aza-Michael additions of indoles catalyzed by chiral phosphoric acids. Angew Chem Int Ed 49:8666-8669. doi: 10.1002/anie.201003919
48. Bandini M, Eichholzer A, Tragni M, Umani-Ronchi A (2008) Enantioselective phase-transfer-catalyzed intramolecular aza-Michael reaction: effective route to pyrazino-indole compounds. Angew Chem Int Ed 47:3238-3241. doi: 10.1002/anie.200705685
49. Chandrasekhar S, Kiran Babu GS, Raji Reddy C (2009) Asymmetric synthesis of aza-diospongin A as an iNOS inducer. Tetrahedron Asymmetry 20:2216-2219. doi: 10.1016/j.tetasy.2009.09.013
50. Liu SW, Hsu HC, Changa CH, Tsai HHG, Hou DR (2010) Asymmetric synthesis of (-)-Lentiginosine by double aza-Michael reaction. Eur J Org Chem 4771-4773. doi: 10.1002/ejoc.201000691
51. Garrido NM, García M, Sánchez MR, Díez D, Urones JG (2010) Enantioselective synthesis of (+)-L-733,060 and (+)-CP-99,994: application of an Ireland-Claisen rearrangement/Michael addition domino sequence. Synlett 387-390. doi: 10.1055/s-0029-1219200
52. Garrido NM, Rosa Sánchez M, Díez D, Sanz F, Urones JG (2011) Enantioselective synthesis of cis-(2 S, 3 R)- and trans-(2 S, 3 S)-piperidinedicarboxylic acids using domino: allylic acetate and Ireland-Claisen rearrangements and Michael addition as the key steps. Tetrahedron Asymmetry 22:872-880. doi: 10.1016/j.tetasy.2011.04.015
53. Garrido NM, García M, Díez D, Sánchez MR, Sanz F, Urones JG (2008) Diastereoselective synthesis of δ -aminoacids through domino Ireland-Claisen rearrangement and Michael addition. Org Lett 10:1687-1690. doi: 10.1021/ol8001464
54. Nishiguchi S, Sydnes MO, Taguchi A, Regnier T, Kajimoto T, Node M, Yamazaki Y, Yakushiji F, Kiso Y, Hayashi Y (2010) Total synthesis of (+)-negamycin and its 5-epi-derivative. Tetrahedron 66:314-320. doi: 10.1016/j.tet.2009.10.097
55. Gärtner M, Weihofen R, Helmchen G (2011) Enantioselective synthesis of 2,5-disubstituted pyrrolidines based on iridium-catalyzed allylic aminations-total synthesis of alkaloids from amphibian skins. Chem Eur J 17:7605-7622. doi: 10.1002/chem.201100649
56. Enders D, Liebich JX, Raabe G (2010) Organocatalytic asymmetric synthesis of trans-1,3-disubstituted tetrahydroisoquinolines via a reductive amination/aza-Michael sequence. Chem Eur J 16:9763-9766. doi: 10.1002/chem.201001623
57. Enders D, Narine AA, Toulgoat F, Bisschops T (2008) Asymmetric Brønsted acid catalyzed isoindoline synthesis: enhancement of enantiomeric ratio by stereoablative kinetic resolution. Angew Chem Int Ed 47:5661-5665. doi: 10.1002/anie.200801354
58. Enkisch C, Schneider C (2009) Sequential Mannich-aza-Michael reactions for the stereodivergent synthesis of highly substituted pyrrolidines. Eur J Org Chem 32:5549-5564. doi: 10.1002/ejoc.200900787
59. Lin S, Zhao GL, Deiana L, Sun J, Zhang Q, Leijonmarck H, Còrdova A (2010) Dynamic kinetic asymmetric domino oxa-Michael/carbocyclization by combination of transition-metal and amine catalysis: catalytic enantioselective synthesis of dihydrofurans. Chem Eur J 47:13930-13934. doi: 10.1002/chem. 201001992
60. Alemán J, Núñez A, Marzo L, Marcos V, Alvarado C (2010) Asymmetric synthesis of 4-amino- 4 H -chromenes by organocatalytic oxa-Michael/aza-Baylis-Hillman tandem reactions. Chem Eur J 31:9453-9456. doi: 10.1002/chem.201001293
61. Hong BC, Kotame P, Tsal CW, Liao JH (2010) Enantioselective total synthesis of (+)-conicol via cascade three-component organocatalysis. Org Lett 4:776-779. doi: 10.1021/ol902840x
62. Xia AB, Xu DQ, Luo SP, Jiang JR, Tang J, Wang YF, Xu ZY (2010) Dual organocatalytic ion-pair assemblies: a highly efficient approach for the enantioselective oxa-Michael-Mannich reaction of salicylic aldehydes with cyclohexenones. Chem Eur J 16:801-804. doi: 10.1002/chem.200902540
63. Liu K, Woggon WD (2010) Enantioselective synthesis of daurichromenic acid and confluentin. Eur J Org Chem 1033-1036. doi: 10.1002/ejoc.200901403
64. Alemán J, Alvarado C, Marcos V, Núñez A, Garcíaruano JL (2011) Synthesis of 4-hydroxy- 4 H -chromenes by reaction of salicylic aldehydes with alkynals catalyzed by silyl prolinol ethers. Synthesis 1840-1846. doi: 10.1055/s-0030-1260020
65. Xu DQ, Wang YF, Luo SP, Zhang S, Zhong AG, Chen H, Xu ZY (2008) A novel enantioselective catalytic tandem oxa-Michael-Henry reaction: one-pot organocatalytic asymmetric synthesis of 3-nitro- 2 H -chromenes. Adv Synth Catal 350:2610-2616. doi: 10.1002/adsc.200800535
66. Andersen NR, Hansen SG, Bertelsen S, Jørgensen KA (2009) Organocatalysis in natural product synthesis: a simple one-pot approach to optically active β -diols. Adv Synth Catal 351:3193-3198. doi: 10.1002/adsc.200900707
67. Wang L, Liu X, Dong Z, Fu X, Feng X (2008) Asymmetric intramolecular oxa-Michael addition of activated α, β -unsaturated ketones catalyzed by a chiral N, N -dioxide nickel(II) complex: highly enantioselective synthesis of flavanones. Angew Chem Int Ed 47:8670-8673. doi: 10.1002/anie.200803326
68. Russo A, Lattanzi A (2008) Catalytic asymmetric β -peroxidation of nitroalkenes. Adv Synth Catal 350:1991-1995. doi: 10.1002/adsc.200800387
69. Carpenter RD, Fettinger JC, Lam KS, Kurth MJ (2008) Asymmetric catalysis: resin-bound hydroxyprolylthreonine derivatives in enamine-mediated reactions. Angew Chem Int Ed 47:6407-6410. doi: 10.1002/anie.200801811
70. Saito N, Ryoda A, Nakanishi W, Kumamoto T, Ishikawa T (2008) Guanidine-catalyzed asymmetric synthesis of 2,2-disubstituted chromane skeletons by intramolecular oxa-Michael addition. Eur J Org Chem 2759-2766. doi: 10.1002/ejoc.200800089
71. Wang HF, Cui HF, Chai Z, Li P, Zheng CW, Yang YQ, Zhao G (2009) Asymmetric synthesis of fluorinated flavanone derivatives by an organocatalytic tandem intramolecular oxa-Michael addition/electrophilic fluorination reaction by using bifunctional cinchona alkaloids. Chem Eur J 15:13299-13303. doi: 10.1002/chem.200902303
72. Reyes E, Talavera G, Vicario JL, Badia D, Carrillo L (2009) Enantioselective organocatalytic domino oxa-Michael/aldol/hemiacetalization: synthesis of polysubstituted furofuranes containing four stereocenters. Angew Chem Int Ed 48:5701-5704. doi: 10.1002/anie.200901333
73. Li DR, Murugan A, Falck JR (2008) Enantioselective, organocatalytic oxy-Michael addition to γ / δ -hydroxy- α, β -enones: boronate-amine complexes as chiral hydroxide synthons. J Am Chem Soc 130:46-48. doi: 10.1021/ja076802c
74. Hiebel MA, Pelotier B, Lhoste P, Piva O (2008) Synthesis of bistramide A and analogues, part 1: stereoselective access to normethyl tetrahydropyran subunit. Synlett 1202-1204. doi: 10.1055/s-2008-1072714
75. Dong CG, Henderson JA, Kaburagi Y, Sasaki T, Kim DS, Kim JT, Urabe D, Guo H, Kishi Y (2009) New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: reductive cyclization and oxy-Michael cyclization approaches. J Am Chem Soc 131:15642-15646. doi: 10.1021/ja9058487
76. Lee H, Kim KW, Park J, Kim H, Kim S, Kim D, Hu X, Yang W, Hong J (2008) A general strategy for construction of both 2,6-cis- and 2,6-trans-disubstituted tetrahydropyrans: substrate-controlled asymmetric total synthesis of (+)-scanlonenyne. Angew Chem Int Ed 47:4200-4203. doi: 10.1002/anie.200705663
77. Robertson J, North C, Sadig JER (2011) Asymmetric synthesis of the C(6-18) bis(tetrahydropyran)spiroacetal fragment of the lituarines. Tetrahedron 67:5011-5023. doi: 10.1016/j.tet.2011.03.116
78. Trost BM, Yang H, Brindle CS, Dong G (2011) Atom-economic and stereoselective syntheses of the ring A and B subunits of the bryostatins. Chem Eur J 17:9777-9788. doi: 10.1002/chem.201002930
79. Fang L, Chen Y, Huang J, Liu L, Quan J, Li CC, Yang Z (2011) Formal synthesis of cortistatins. J Org Chem 76:2479-2487. doi: 10.1021/jo102202t
80. Galzerano P, Pesciaioli F, Mazzanti A, Bartoli G, Melchiorre P (2009) Asymmetric organocatalytic cascade reactions with α -substituted α, β -unsaturated aldehydes. Angew Chem Int Ed 48:7892-7894. doi: 10.1002/anie.200903803
81. Zhao GL, Veselý J, Rios R, Ibrahem I, Sundén H, Córdova A (2008) Highly diastereo- and enantioselective catalytic domino thia-Michael/aldol reactions: synthesis of benzothiopyrans with three contiguous stereocenters. Adv Synth Catal 350:237-242. doi: 10.1002/adsc.200700407
82. Yoshida M, Ohno Y, Hara S (2010) Organocatalytic asymmetric thio-Michael addition of arylmethyl mercaptans to cyclic enones by a primary amino acid. Tetrahedron Lett 51:5134-5136. doi: 10.1016/j.tetlet.2010.07.089
83. Wang XF, Hua QL, Cheng Y, An XL, Yang QQ, Chen JR, Xiao WJ (2010) Organocatalytic asymmetric sulfa-Michael/Michael addition reactions: a strategy for the synthesis of highly substituted chromans with a quaternary stereocenter. Angew Chem Int Ed 49:8379-8383. doi: 10.1002/anie.201004534
84. Lu HH, Zhang FG, Meng XG, Duan SW, Xiao W (2009) Enantioselective Michael reactions of β, β -disubstituted nitroalkenes: a new approach to β 2, 2 -amino acids with hetero-quaternary stereocenters. Org Lett 11:3946-3949. doi: 10.1021/ol901572x
85. Zhao D, Yuan Y, Chan ASC, Wang R (2009) Highly enantioselective 1,4-addition of diethyl phosphite to enones using a dinuclear Zn catalyst. Chem Eur J 15:2738-2741. doi: 10.1002/chem.200802688
86. Zhao D, Mao L, Yang D, Wang R (2010) Zinc-mediated asymmetric additions of dialkylphosphine oxides to α, β -unsaturated ketones and N -sulfinylimines. J Org Chem 75:6756-6763. doi: 10.1021/jo1014917
87. Zhu Y, Malerich JP, Rawal VH (2010) Squaramide-catalyzed enantioselective Michael addition of diphenyl phosphite to nitroalkenes. Angew Chem Int Ed 49:153-156. doi: 10.1002/anie.200904779
88. Zhao D, Wang Y, Mao L, Wang R (2009) Highly enantioselective conjugate additions of phosphites to α, β -unsaturated N -acylpyrroles and imines: a practical approach to enantiomerically enriched amino phosphonates. Chem Eur J 15:10983-10987. doi: 10.1002/chem.200901901
89. Zhao D, Mao L, Wang Y, Yang D, Zhang Q, Wang R (2010) Catalytic asymmetric hydrophosphinylation of α, β -unsaturated N -acylpyrroles: application of dialkyl phosphine oxides in enantioselective synthesis of chiral phosphine oxides or phosphines. Org Lett 12:1880-1882. doi: 10.1021/ol100504h