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Synthesis 2017; 49(24): 5285-5306
DOI: 10.1055/s-0036-1590909
DOI: 10.1055/s-0036-1590909
short review
Computer-Aided Insight into the Relative Stability of Enamines
The authors acknowledge the Spanish Government for financial support (CTQ2015-71506R, FEDER). A.C.A. is grateful to Fundació Privada Cellex de Barcelona for a fellowship. H.C. has a studentship of the Spanish Government (CTQ2012-39230, FEDER).
Further Information
Publication History
Received: 10 July 2017
Accepted after revision: 23 August 2017
Publication Date:
04 October 2017 (online)
Dedicated to Pere Mir, in memoriam
Abstract
Venerable aldol, Michael, and Mannich reactions have undergone a renaissance in the past fifteen years, as a consequence of the development of direct organocatalytic versions, mediated by chiral amines. Chiral enamines are key intermediates in these reactions. This review focuses on the formation of enamines from secondary amines and their relative thermodynamic stability, as well as on the reverse reactions (hydrolysis). Experimental results and predictions based on MO calculations are reviewed to show which enamine forms may predominate in the reaction medium and to compare several secondary amines as organocatalysts.
1 Introduction
2 Relative Stability of Enamines as Determined Experimentally
3 Pyrrolidine Enamines
4 Enamines of the Jørgensen–Hayashi Catalyst
5 Proline Enamines
6 Free Enthalpies and Polar Solvent Effects
7 Comparison of Organocatalysts
8 Summary and Outlook
9 Appendix
-
References
- 1a Hickmott PW. Tetrahedron 1982; 38: 1975
- 1b Stork G. Med. Res. Rev. 1999; 19: 370
- 1c Stork G. Tetrahedron 2011; 67: 9754
- 1d Seebach D. Beck AK. Badine DM. Limbach M. Eschenmoser A. Treasurywala AM. Hobi R. Prikoszovich W. Linder B. Helv. Chim. Acta 2007; 90: 425
- 2a Nitroalkenes: Alonso DA. Baeza A. Chinchilla R. Gómez C. Guillena G. Pastor IM. Ramón DJ. Molecules 2017; 22: 895
- 2b Catalysis by Pro: Liu J. Wang L. Synthesis 2017; 49: 960
- 2c Aldol: Heravi MM. Zadsirjan V. Dehghani M. Hosseintash N. Tetrahedron: Asymmetry 2017; 28: 58
- 2d Nitroalkenes, other electrophiles: Burés J. Armstrong A. Blackmond DG. Acc. Chem. Res. 2016; 49: 214
- 2e Ethanal: Kumar M. Kumar A. Rizvi MA. Shah BA. RSC Adv. 2015; 5: 55926
- 2f Enamine catalysis: Desmarchelier A. Coeffard V. Moreau X. Greck C. Tetrahedron 2014; 70: 2491
- 2g H-Bonding: Albrecht L. Jiang H. Jørgensen KA. Chem. Eur. J. 2014; 20: 358
- 2h Aldol: Mase N. Hayashi Y. In Comprehensive Organic Synthesis . 2nd ed.; Knochel P. Molander GA. 2014
- 2i Mannich: Cai X. Xie B. ARKIVOC 2013; (i): 264
- 2j Intermolecular aldol: Yliniemela-Sipari SM. Piisola A. Pihko PM. In Science of Synthesis, Asymmetric Organocatalysis . Vol. 1. List B. Maruoka K. Thieme; Stuttgart: 2012: 35
- 2k Diarylprolinol silyl ethers: Jensen KL. Dickmeiss G. Jiang H. Albrecht L. Jørgensen KA. Acc. Chem. Res. 2012; 45: 248
- 2l Mechanisms: Nielsen M. Worgull D. Zweifel T. Gschwend B. Bertelsen S. Jørgensen KA. Chem. Commun. 2011; 47: 632
- 2m Afewerki S. Cordova A. Chem. Rev. 2016; 116: 13512
- 2n Meazza M. Rios R. Synthesis 2016; 48: 960
- 2o Marigo M. Wabnitz TC. Fielenbach D. Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
- 2p Hayashi Y. Gotoh H. Hayashi T. Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
- 3a Bahmanyar S. Houk KN. Martin HJ. List B. J. Am. Chem. Soc. 2003; 125: 2475 ; [among 24 reasonable TSs for the Pro-catalyzed aldol reactions, 8 of those involving H bonding were investigated at the B3LYP/6-31G level]
- 3b Armstrong A. Boto RA. Dingwall P. Contreras-Garcia J. Harvey MJ. Mason NJ. Rzepa HS. Chem. Sci. 2014; 5: 2057
- 3c Bakr BW. Sherrill CD. Phys. Chem. Chem. Phys. 2016; 18: 10297
- 4a Bock DA. Lehmann CW. List B. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20636
- 4b Blackmond DG. Moran A. Hughes M. Armstrong A. J. Am. Chem. Soc. 2010; 132: 7598
- 4c Schmid MB. Zeitler K. Gschwind RM. Angew. Chem. Int. Ed. 2010; 49: 4997
- 4d Kanzian T. Lakhdar S. Mayr H. Angew. Chem. Int. Ed. 2010; 49: 9526
- 4e Mayr H. Lakhdar S. Maji B. Ofial AR. Beilstein J. Org. Chem. 2012; 8: 1458
- 4f Fu A. Tian C. Li H. Li P. Chu T. Wang Z. Liu J. Chem. Phys. 2015; 455: 65; and refs cited therein
- 4g Ashley MA. Hirschi JS. Izzo JA. Vetticatt MJ. J. Am. Chem. Soc. 2016; 138: 1756; and refs cited therein
- 5a Schmid MB. Zeitler K. Gschwind RM. Chem. Sci. 2011; 2: 1793
- 5b Hayashi J. Okamura D. Yamazaki T. Ameda Y. Gotoh H. Tsuzuki S. Uchimaru T. Seebach D. Chem. Eur. J. 2014; 20: 17077
- 5c Halskov KS. Donslund BS. Paz BM. Jørgensen KA. Acc. Chem. Res. 2016; 49: 974 ; and refs cited therein
- 6 Sánchez D. Carneros H. Castro-Alvarez A. Llácer E. Planas F. Vilarrasa J. Tetrahedron Lett. 2016; 57: 5254 ; and refs cited therein
- 7a Schmid MB. Zeitler K. Gschwind RM. J. Org. Chem. 2011; 76: 3005 ; and refs cited therein
- 7b List B. J. Am. Chem. Soc. 2000; 122: 9336
- 7c Notz W. Tanaka F. Watanabe S. Chowdari NS. Turner JM. Thayumanavan R. Barbas CF. J. Org. Chem. 2003; 68: 9624
- 8a Sakthivel K. Notz W. Bui T. Barbas CF. J. Am. Chem. Soc. 2001; 123: 5260
- 8b Cobb AJ. A. Shaw DM. Ley SV. Synlett 2004; 558
- 8c Saito S. Yamamoto H. Acc. Chem. Res. 2004; 37: 570
- 8d Vishnumaya MR. Singh VK. J. Org. Chem. 2009; 74: 4289
- 8e Nakashima E. Yamamoto H. Chem. Asian J. 2017; 12: 41 ; and refs cited therein
- 9a Sánchez D. Bastida D. Burés J. Isart C. Pineda O. Vilarrasa J. Org. Lett. 2012; 14: 536 ; and refs cited therein
- 9b Rodríguez-Escrich C. Master’s Thesis. Universitat de Barcelona; Spain: 2004
- 9c Isart C. DEA Thesis. Universitat de Barcelona; Spain: 2007
- 9d Isart C. Burés J. Vilarrasa J. Tetrahedron Lett. 2008; 49: 5414
- 9e Sánchez D. Master’s Thesis. Universitat de Barcelona; Spain: 2009
- 9f Isart C. Ph.D. Dissertation. Universitat de Barcelona; Spain: 2012
- 9g Carneros H. Master’s Thesis. Universitat de Barcelona; Spain: 2012
- 9h Sánchez D. Castro-Alvarez A. Vilarrasa J. Tetrahedron Lett. 2013; 54: 6381
- 9i Carneros H. Sánchez D. Vilarrasa J. Org. Lett. 2014; 16: 2900
- 9j Sánchez D. Ph.D. Dissertation. Universitat de Barcelona; Spain: 2015
- 9k Castro-Alvarez A. Carneros H. Sánchez D. Vilarrasa J. J. Org. Chem. 2015; 80: 11977
- 9l Castro-Alvarez, A., unpublished results (Ph.D. dissertation in preparation).
- 9m Carneros, H., unpublished results (Ph.D. dissertation in preparation).
- 10a Ahrendt KA. Borths CJ. MacMillan DW. C. J. Am. Chem. Soc. 2000; 122: 4243
- 10b Austin JF. MacMillan DW. C. J. Am. Chem. Soc. 2002; 124: 1172
- 11a Beeson TD. Mastracchio A. Hong J.-B. Ashton K. MacMillan DW. C. Science 2007; 582
- 11b Um JM. Gutierrez O. Schoenebeck F. Houk KN. MacMillan DW. C. J. Am. Chem. Soc. 2010; 132: 6001
- 11c Mastracchio A. Warkentin AA. Walji AM. MacMillan DW. C. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20648
- 11d Tisovsky P. Meciarova M. Sebesta R. Org. Biomol. Chem. 2014; 12: 9446
- 12a Liu F. Wang S. Wang N. Peng Y. Synlett 2007; 2415
- 12b Wang C. Yu C. Liu C. Peng Y. Tetrahedron Lett. 2009; 50: 2363
- 13a Enamines + 1,2,3-triazines: Prieto P. Cossío FP. Carrillo JR. de la Hoz A. Díaz-Ortiz A. Moreno A. J. Chem. Soc., Perkin Trans. 2 2002; 1257
- 13b Nitroso aldol: Akakura M. Kawasaki M. Yamamoto H. Eur. J. Org. Chem. 2008; 4245
- 13c [3+2]-Cycloadditions: Lopez SA. Munk ME. Houk KN. J. Org. Chem. 2013; 78: 1576
- 13d E/Z Alkoxy-enamines: Mukaiyama T. Uchimaru T. Hayashi Y. Bull. Chem. Soc. Jpn. 2016; 89: 455
- 14a Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Scalmani G. Barone V. Petersson GA. Nakatsuji H. Li X. Caricato M. Marenich A. Bloino J. Janesko BG. Gomperts R. Mennucci B. Hratchian HP. Ortiz JV. Izmaylov AF. Sonnenberg JL. Williams-Young D. Ding F. Lipparini F. Egidi F. Goings J. Peng B. Petrone A. Henderson T. Ranasinghe D. Zakrzewski VG. Gao J. Rega N. Zheng G. Liang W. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Vreven T. Throssell K. Montgomery JA. Jr. Peralta JE. Ogliaro F. Bearpark M. Heyd JJ. Brothers E. Kudin KN. Staroverov VN. Keith T. Kobayashi R. Normand J. Raghavachari K. Rendell A. Burant JC. Iyengar SS. Tomasi J. Cossi M. Millam JM. Klene M. Adamo C. Cammi R. Ochterski JW. Martin RL. Morokuma K. Farkas O. Foresman JB. Fox DJ. Gaussian 09 package (Revision D.01, 2013), Gaussian 09. Revision D.01. Gaussian, Inc; Wallingford: 2013. www.gaussian.co
- 14b Becke AD. J. Chem. Phys. 1993; 98: 5648
- 14c Stephens PJ. Devlin FJ. Chabalowski CF. Frisch MJ. J. Phys. Chem. 1994; 98: 11623
- 14d Møller C. Plesset MS. Phys. Rev. 1934; 46: 618
- 14e Head-Gordon M. Pople JA. Frisch MJ. Chem. Phys. Lett. 1988; 153: 503
- 14f Zhao Y. Truhlar DG. Theor. Chem. Acc. 2008; 120: 215
- 14g Zhao Y. Truhlar DG. Acc. Chem. Res. 2008; 41: 157
- 14h Marenich AV. Cramer CJ. Truhlar DG. J. Phys. Chem. B 2009; 113: 6378
- 14i ORCA 3.0.2, The ORCA program system, Wiley Interdiscip. Rev.: Neese F. Comput. Mol. Sci. 2012; 2: 73
- 15a https://www.schrodinger.com/macromodel (MacroModel, Schrödinger, LLC, New York, NY).
- 15b Banks JL. Beard HS. Cao Y. Cho AE. Damm W. Farid R. Felts AK. Halgren TA. Mainz DT. Maple JR. Murphy R. Philipp DM. Repasky MP. Zhang LY. Berne BJ. Friesner RA. Gallicchio E. Levy RM. J. Comput. Chem. 2005; 26: 1752 ; OPLS2005 parameters
- 17 We carried out additional experiments that confirm the relative position of 2-methylpropanal (isobutyraldehyde) and 2-methylcyclohexanone (2MC) in Figure 2 and the Appendix. For example, when a solution of the pyrrolidine–cyclohexanone enamine was prepared from its components in the presence of 3 Å molecular sieves and CaH2, and 100 mol% of 3-methylbutanal was added, we observed by 1H NMR that in DMSO-d 6 the peaks at δ = 4.10 (enamine proton, t, J = 3.9 Hz) and 2.92 (4 H α to the N atom) started to disappear and signals at δ = 5.57 (new enamine proton) and 2.85 (4 H α to the N atom) appeared, and the equilibrium was reached in less than 1 h (K eq ≈ 28); three days later the ratios between carbonyl compounds and their enamines were maintained. A similar result was observed in CD3CN. In contrast, when we added commercially available 2MC to the pyrrolidine–cyclohexanone enamine, in DMSO-d 6, only a slight decrease of the peaks of the cyclohexanone enamine was observed whereas the peaks of the 2MC enamine were hardly observable; however, by adding 10 equiv of 2MC the exchange was clearly seen; an approximate value of K eq (0.03) was determined.
- 18 A trace of water or of pyrrolidine may catalyze these exchange reactions. For example, a trace of water hydrolyzes a small amount of pyrrolidine–cyclohexanone enamine and the resulting pyrrolidine reacts with carbonyl A leading to the production of water, which repeats the cycle. Eventually, equilibrium is reached. Similarly, a trace of pyrrolidine remaining in the vial, by reacting with carbonyl compound A gives some enamine A plus some water, which continues the exchange process, as above. Although other exchange mechanisms might be operative, they have not yet been demonstrated.
- 19 For malonaldehyde (propanedial) the calculated total energies of the main conformer are –267.13926 [B3LYP/6-31G(d)], –266.35922 [MP2/6-31G(d)//B3LYP/6-31G(d)], and –266.51761 a.u. [MP2/6-311+G(d,p)//B3LYP/6-31G(d)]. For its enol with an intramolecular hydrogen bond, (Z)-3-hydroxypropenal, the values are –267.14885, –266.36273, and –266.52384 a.u., respectively (that is, a few kcal/mol lower at every level). Thus, ΔE r in Figure 2 would be –15.6 instead of –17.8 (still the ‘best’ carbonyl compound in Figure 2); this is the only case of our series in which an enol form is more stable than the lowest-energy carbonyl form, in the gas phase.
- 20a Ref. 2k.
- 20b Arceo E. Melchiorre P. Angew. Chem. Int. Ed. 2012; 51: 5290
- 20c Li J.-L. Liu T.-Y. Chen Y.-C. Acc. Chem. Res. 2012; 45: 1491
- 20d Kumar I. Ramaraju P. Mir NA. Org. Biomol. Chem. 2013; 11: 709
- 20e Reboredo S. Parra A. Alemán J. Asymmetric Catal. 2014; 1: 24
- 20f Vicario JL. Synlett 2016; 27: 1006
- 20g Marcos V. Alemán J. Chem. Soc. Rev. 2016; 45: 6812
- 20h Chauhan P. Kaya U. Enders D. Adv. Synth. Catal. 2017; 359: 888
- 20i Klier L. Tur F. Poulsen PH. Jørgensen KA. Chem. Soc. Rev. 2017; 46: 1080
- 20j Lagiewka B. Albrecht L. Asian J. Org. Chem. 2017; 6: 516
- 20k Dieckmann A. Breugst M. Houk KN. J. Am. Chem. Soc. 2013; 135: 3237
- 20l Seegerer A. Hioe J. Hammer MM. Morana F. Fuchs PJ. W. Gschwind RM. J. Am. Chem. Soc. 2016; 138: 9864 ; and refs therein
- 21 Seebach D. Groselj U. Badine DM. Schweizer WB. Beck AK. Helv. Chim. Acta 2008; 91: 1999
- 22a Groselj U. Seebach D. Badine DM. Schweizer WB. Beck AK. Krossing I. Klose P. Hayashi Y. Uchimaru T. Helv. Chim. Acta 2009; 92: 1225
- 22b Cassani C. Melchiorre P. Org. Lett. 2012; 14: 5590
- 22c Seebach D. Sun X. Sparr C. Ebert M.-O. Schweizer WB. Beck AK. Helv. Chim. Acta 2012; 95: 1064
- 22d Seebach D. Sun X. Ebert M.-O. Schweizer WB. Purkayastha N. Beck AK. Duschmale J. Wennemers H. Mukaiyama T. Benohoud M. Hayashi Y. Reiher M. Helv. Chim. Acta 2013; 96: 799
- 22e Lakhdar S. Maji B. Mayr H. Angew. Chem. Int. Ed. 2012; 51: 5739
- 22f Erdmann H. An F. Mayer P. Ofial AR. Lakhdar S. Mayr H. J. Am. Chem. Soc. 2014; 136: 14263
- 23a Franzen J. Marigo MD. Fielenbach D. Wabnitz TC. Jørgensen KA. J. Am. Chem. Soc. 2005; 127: 18296
- 23b Bertelsen S. Marigo M. Brandes S. Dinér P. Jørgensen KA. J. Am. Chem. Soc. 2006; 128: 12973
- 23c Dinér P. Kjærsgaard A. Lie MA. Jørgensen KA. Chem. Eur. J. 2008; 14: 122
- 23d Zhao J.-Q. Gan L.-H. Eur. J. Org. Chem. 2009; 2661
- 23e Ref. 22a.
- 23f Hutka M. Polácková V. Marák J. Kaniansky D. Sebesta R. Toma S. Eur. J. Org. Chem. 2010; 6430
- 23g Ref. 5b [conformational population, M06-2X/6-311+G(2df,2p)//B3LYP/6-31G, phenylethanal].
- 23h Ref. 5c (enamines, dienamines, trienamines, and cross-trienamines of the J–H catalyst).
- 23i Moberg C. Angew. Chem. Int. Ed. 2013; 52: 2160
- 23j Sahoo G. Rahaman H. Madarász A. Pápai I. Melarto M. Valkonen A. Pihko PM. Angew. Chem. Int. Ed. 2012; 51: 13144
- 23k Sun H. Zhang D. Zhang C. Liu C. Chirality 2010; 22: 813
- 23l Gan L.-H. Zhou J. Guo X. J. Theor. Comput. Chem. 2013; 12: 1350004/1
- 24a Grimme S. J. Comput. Chem. 2006; 27: 1787
- 24b Ehrlich S. Moellmann J. Grimme S. Acc. Chem. Res. 2013; 46: 916
- 25a Allinger NL. Zhu ZQ. S. Chen K. J. Am. Chem. Soc. 1992; 114: 6120
- 25b Wiberg KB. Ochterski J. Streitwieser A. J. Am. Chem. Soc. 1996; 118: 8291
- 25c Dimerization energy: Colominas C. Teixidó J. Cemeli J. Luque FJ. Orozco M. J. Phys. Chem. B 1998; 102: 2269
- 25d Da Silva CO. Da Silva EC. Nascimento MA. C. J. Phys. Chem. A 1999; 103: 11194
- 26a Lam Y. Grayson MN. Holland MC. Simon A. Houk KN. Acc. Chem. Res. 2016; 49: 750
- 26b Cheong PH.-Y. Legault CY. Um JM. Celebi-Olcum N. Houk KN. Chem. Rev. 2011; 111: 5042
- 26c TS, Mannich vs. aldol: Bahmanyar S. Houk KN. Org. Lett. 2003; 5: 1249
- 26d Nitro-Michael: Patil MP. Sunoj RB. Chem. Eur. J. 2008; 14: 10472
- 26e Mannich, syn/anti: Fu A. Li H. Si H. Yuan S. Duan Y. Tetrahedron: Asymmetry 2008; 19: 2285
- 26f Mannich: Parasuk W. Parasuk V. J. Org. Chem. 2008; 73: 9388
- 26g Mannich, heterocyclic substrate: Li H. Fu A. Shi H. J. Mol. Catal. A: Chem. 2009; 303: 1
- 26h Aldol, Houk–List model: Sharma K. Sunoj RB. Angew. Chem. Int. Ed. 2010; 49: 6373
- 26i Mannich, CH3CHO: Ajitha MJ. Suresh CH. J. Comput. Chem. 2011; 32: 1962
- 26j Mannich, CH3CHO: Chang Q. Zhou J. Gan L.-H. J. Phys. Org. Chem. 2012; 25: 667
- 26k Nitro-Michael: Yang H. Wong MW. Org. Biomol. Chem. 2012; 10: 3229
- 26l Nitro-Michael, explicit solvent: Sharma AK. Sunoj RB. J. Org. Chem. 2012; 77: 10516
- 26m Nitro-Michael, role of PhCOOH: Shi H. Huang X. Liu G. Yu K. Xu C. Li W. Zeng B. Tang Y. Int. J. Quant. Chem. 2013; 113: 1339
- 26n COO– vs. COOH: Hubin PO. Jacquemin D. Leherte L. Vercauteren DP. Chem. Phys. 2014; 434: 30
- 27a Nugent TC. Spiteller P. Hussain I. Hussein HA. E. D. Najafian FT. Adv. Synth. Catal. 2016; 358: 3706
- 27b Nugent TC. Najafian FT. Hussein HA. E. D. Hussain I. Chem. Eur. J. 2016; 22: 14342
- 28a Martinez A. Zumbansen K. Dohring A. van Gemmeren M. List B. Synlett 2014; 25: 932
- 28b List B. Lerner RA. Barbas CF. J. Am. Chem. Soc. 2000; 122: 2395
- 28c Notz W. List B. J. Am. Chem. Soc. 2000; 122: 7386
- 28d Comparison of 21 catalysts: Sakthivel K. Notz W. Bui T. Barbas CF. J. Am. Chem. Soc. 2001; 123: 5260
- 28e List B. Pojarliev P. Castello C. Org. Lett. 2001; 3: 573
- 28f Nyberg AI. Usano A. Pihko PM. Synlett 2004; 1891
- 28g Ref. 8e.
- 28h Niessing S. Czekelius C. Janiak C. Catal. Commun. 2017; 95: 12
- 28i Porcar R. Burguete MI. Lozano P. Garcia-Verdugo E. Luis SV. ACS Sustainable Chem. Eng. 2016; 4: 6062
- 28j Gurka AA. Szori K. Szollosi G. Bartok M. London G. Tetrahedron Lett. 2015; 56: 7201 ; and refs therein
- 29a Mahrwald R. Richter C. Krumrey M. Klaue K. Eur. J. Org. Chem. 2016; 5309
- 29b Ramachary DB. Shruthi KS. J. Org. Chem. 2016; 81: 2405
- 29c Zhang Q. Cui X. Zhang L. Luo S. Wang H. Wu Y. Angew. Chem. Int. Ed. 2015; 54: 5210
- 29d Moles FJ. N. Guillena G. Nájera C. Gómez-Bengoa E. Synthesis 2015; 47: 549
- 29e Triandafillidi I. Bisticha A. Voutyritsa E. Galiatsatou G. Kokotos CG. Tetrahedron 2015; 71: 932
- 30a With the J–H catalyst, the related values, in kcal/mol, are as follows: propanedial, ΔE –19.7, ΔG ѳ –18.6, ΔG ѳ(DMSO) –20.5, ΔG ѳ(H2O) –22.1; PhCH2CHO, ΔE –10.3, ΔG ѳ –10.4, ΔG ѳ(DMSO) –12.8, ΔG ѳ(H2O) –12.7; Me2CHCH2CHO, ΔE –5.0, ΔG ѳ –5.6, ΔG ѳ(DMSO) –7.3, ΔG ѳ(H2O) –6.6; Me3CCOMe, enamine ap, ΔE 6.3, ΔG ѳ 7.4, ΔG ѳ(DMSO) 7.5, ΔG ѳ(H2O) 7.6; Me3CCOMe, sc-exo, ΔE 10.3, ΔG ѳ 11.4, ΔG ѳ(DMSO) 10.5, ΔG ѳ (H2O) 9.9.
- 30b With Pro, the values are as follows: propanedial, CO2H s-cis, ΔE –11.5, ΔG ѳ –13.4, ΔG ѳ(DMSO) –13.0, ΔG ѳ(H2O) –15.6; propanedial, s-trans, ΔE –8.7, ΔG ѳ –10.4, ΔG ѳ(DMSO) –12.6, ΔG ѳ(H2O) –14.3; PhCH2CHO, s-cis, ΔE –5.5, ΔG ѳ –6.7, ΔG ѳ(DMSO) –6.4, ΔG ѳ(H2O) –7.6; Me2CHCH2CHO, s-trans, ΔE –1.8, ΔG ѳ –2.9, ΔG ѳ(DMSO) –4.4, ΔG ѳ(H2O) –4.0; EtCHO, s-trans, ΔE –1.1, ΔG ѳ –1.6, ΔG ѳ(DMSO) –2.7, ΔG ѳ(H2O) –2.5; Me3CCOMe, s-cis, ΔE 9.4, ΔG ѳ 10.6, ΔG ѳ(DMSO) 12.3, ΔG ѳ(H2O) 11.2.
- 31a Pyrrolidine-sulfonamide, nitro-Michael: Wang J. Li H. Lou B. Zu L. Guo H. Wang W. Chem. Eur. J. 2006; 12: 4321
- 31b 5-(Pyrrolidin-2-yl)tetrazole: Arnó M. Zaragozá RJ. Domingo LR. Tetrahedron: Asymmetry 2007; 18: 157
- 31c Pro-NHSO2Ar, Mannich: Veverková E. Strasserová J. Sebesta R. Toma S. Tetrahedron: Asymmetry 2010; 21: 58
- 31d 4-OH-pyrrolidine derivatives, Mannich anti-selective: Gómez-Bengoa E. Maestro M. Mielgo A. Otazo I. Palomo C. Velilla I. Chem. Eur. J. 2010; 16: 5333
- 31e Pyrrolidine-ureas, nitro-Michael: Cao X.-Y. Zheng J.-C. Li Y.-X. Shu Z.-C. Sun X.-L. Wang B.-Q. Tang Y. Tetrahedron 2010; 66: 9703
- 31f 2-CHPh2 and 2-CPh2OMe, MVK: Patil MP. Sharma AK. Sunoj RB. J. Org. Chem. 2010; 75: 7310
- 31g Thiaproline: Parasuk W. Parasuk V. Comput. Theor. Chem. 2011; 964: 133
- 31h Mannich, thiaproline: Parasuk W. Parasuk V. Asian J. Org. Chem. 2013; 2: 85
- 31i 4-OH-prolinamides, nitro-Michael: Watts J. Luu L. McKee V. Carey E. Kelleher F. Adv. Synth. Catal. 2012; 354: 1035
- 31j Mannich, 2-(pyrrolidin-1-ylmethyl)pyrrolidine: ref. 26g.
- 31k Pro dipeptides vs. Pro tripeptides, aldol: Szöllösi G. Csámpai A. Somlai C. Fekete M. Bartók M. J. Mol. Catal. A: Chem. 2014; 382: 86
- 31l Pyrrolidinyl-oxazolecarboxamides: Kamal A. Sathish M. Srinivasulu V. Chetna J. Shekar KC. Nekkanti S. Tangella Y. Shankaraiah N. Org. Biomol. Chem. 2014; 12: 8008
- 31m Pro-hydrazide, explicit water: Chakrabarty K. Ghosh A. Basak A. Das GK. Comput. Theor. Chem. 2015; 1062: 11
- 31n For a review, see: ref. 26a.
For historical reviews, see:
Also see:
For a non-exhaustive list of recent reviews of organocatalytic reactions involving enamine chemistry, see:
For the combined use of aminocatalysis and transition-metal catalysis (which will not be dealt with here), see refs cited in:
For the J–H catalyst, see:
For revisions of the Houk–List TS model for aldol reactions, see:
When the carboxyl group is in its anionic form or under basic catalysis (with the carboxyl group in its standard s-cis arrangement), anchimeric assistance is plausible, with an attack of the electrophile from the rear face of the s-cis conformer1d and formation of the corresponding bicyclic exo-oxazolidinone, the more stable of the two possible oxazolidinones formed from aldehydes. For pros and cons of this model and for other models, see:
For pioneering works on organocatalytic Mannich reactions, see:
For entries on the theme, see:
α-Allylation of cyclohexanone(s) via SOMO catalysis required the modification of the standard catalysts, to lower steric hindrance at C2, in order to favor the formation of the starting enamines:
Also see:
Previous QCC of enamines of pyrrolidine:
For excellent reviews of dienamines and trienamines (generally of 2-substituted pyrrolidines, mainly derivatives of the J–H catalyst), see:
For NMR studies (in agreement with the calculations reported here), see:
For calculations of N-(cyclohexadienyl)ethenyl-substituted pyrrolidines, see:
For an excellent summary of the so-called Z/E dilemma and its experimental and QCC-based explanation, see:
For X-ray crystal structures of imidazolidinone-derived enamines, see:
For X-ray crystal structures of 2-Tr and 2-SiPh3-pyrrolidine enamines, see:
For DFT calculations of nitro-Michael reactions, which are a hot topic nowadays due to the relevance of cyclobutane intermediates, see the extensive review of Seebach and co-workers22c,d and references cited therein, ref. 5b and refs therein, and ref. 2d and references cited therein. Also see the following highlight:
For [2+4]-cycloadducts, see ref. 22c and:
For related computational studies, see:
For classical studies on the structure of carboxylic acids (and the corresponding calculations of the s-cis/s-trans forms, formerly so-called syn/anti), see references cited in:
For reviews, see:
Also see:
For aldol reactions of 4-(2-oxopropyl)- and 4-(3-oxopropyl)cyclohexanone derivatives, where the reaction selectively occurs at the cyclohexanone ring, see:
For an outstanding study of Pro-catalyzed aldol reactions of acetone, see:
For pioneering works, see:
For some very recent papers focused on acetone reactions, see:
For aldol reactions of 4-methylcyclohexanone with desymmetrization, see refs cited in: