Allenes in Diels–Alder Cycloadditions

Dedicated to the memory of Klaus Hafner

Abstract

For a long time, allenes—and cumulenic systems in general—played a relatively minor role in Diels–Alder cycloadditions. This situation has changed, since allenes are more readily available and as their unique stereochemical features in [4+2]cycloadditions are more widely recognized. This review presents a comprehensive overview of allenes in Diels–Alder processes using selected examples. Allenes in dienes, dienophiles and cycloadducts are covered, inter- and intramolecular Diels–Alder cycloadditions are discussed, and stereochemical features of the addition process are described. Areas of emerging importance are also covered, including allenic components in dehydro-Diels–Alder processes, and dendralenic allenes in Diels–Alder sequences for the rapid generation of target-relevant molecular complexity. Preparatively useful methods for allenic precursor synthesis are also discussed.

1 Introduction

2 Allenic Dienes

2.1 Vinylallenes

2.2 Bisallenes

2.3 Cross-conjugated Allenes

3 Allenic Dienophiles

4 Intramolecular Diels–Alder Cycloadditions

5 Allenic Cycloadducts

6 Conclusions and Outlook

Key words

Diels–Alder addition - allenes as dienes and dienophiles - intermolecular cycloaddition - intramolecular cycloaddition - stereoselective synthesis - dehydro-Diels–Alder reactions - rapid generation of molecular complexity

Publication History

Received: 18 May 2021

Accepted after revision: 16 June 2021

Article published online:
04 August 2021

• References

• 1 Diels O, Alder K. Justus Liebigs Ann. Chem. 1928; 460: 98
• 2 Nicolaou KC, Snyder SA, Montagnon T, Vassilikogiannakis G. Angew. Chem. Int. Ed. 2002; 41: 1668
• 3 Alder K. In Nobel Lectures, Chemistry 1942-1962 . Elsevier Publishing Company; Amsterdam: 1964: 267-303
• 4a Tanner D, Ascic E. In Comprehensive Organic Synthesis, 2nd ed., Vol. 5. Knochel P, Molander GA. Elsevier; Amsterdam: 2014: 466-517
• 4b Takao K, Munakata R, Tadano K. Chem. Rev. 2005; 105: 4779
• 4c Ciganek E. In Organic Reactions, Vol. 32. Dauben WG. John Wiley & Sons; New York: 1984: 1-374
• 5 Wessig P, Müller G. Chem. Rev. 2008; 108: 2051
• 6 Neff RK, Frantz DE. Tetrahedron 2015; 71: 7
• 7 Hopf H. In The Chemistry of the Allenes, Vol. 2. Landor SR. Academic Press; London: 1982: 525-562
• 8 It should be noted that the cycloadditions discussed in this review are not the only pericyclic reactions that these highly unsaturated hydrocarbons can undergo. Depending on the substrate and the reaction conditions, competing processes such as electrocyclizations and/or sigmatropic hydrogen and carbon shifts may also take place; in other words, transformations that are best rationalized by the Woodward–Hoffmann rules. See Scheme 41 for an example.
• 9 Schön G, Hopf H. Liebigs Ann. Chem. 1981; 165
• 10a Wang X, Donavalova J, Hollis A, Johnson D, Rodriguez A, Kennedy GD, Krishnan G, Banks H. J. Heterocycl. Chem. 1994; 31: 871
• 10b Regás D, Ruiz JM, Afonso MM, Palenzuela JA. J. Org. Chem. 2006; 71: 9153
• 10c Sasaki M, Kondo Y, Moto-ishi T, Kawahata M, Yamaguchi K, Takeda K. Org. Lett. 2015; 17: 1280
• 10d Lo VK.-Y, Chan Y.-M, Zhou D, Toy PH, Che C.-M. Org. Lett. 2019; 21: 7717
• 11a Mokar BD, Liu J, Liu R.-S. Org. Lett. 2018; 20: 1038
• 11b Chen C.-N, Liu R.-S. Angew. Chem. Int. Ed. 2019; 58: 9831
• 12a Regás D, Ruiz JM, Afonso MM, Gallindo A. Tetrahedron Lett. 2003; 44: 8471
• 12b Ruiz JM, Regás D, Afonso MM, Palenzuela JA. J. Org. Chem. 2008; 73: 7246
• 12c Lee K, Lee PH. Bull. Korean Chem. Soc. 2008; 29: 487
• 13 Regás D, Afonso MM, Galindo A, Palenzuela JA. Tetrahedron Lett. 2000; 41: 6781
• 14a Regás D, Afonso MM, Palenzuela JA. Synthesis 2004; 757
• 14b Regás D, Afonso MM, Palenzuela JA. Tetrahedron 2012; 68: 9345
• 14c Regás D, Afonso MM, Rodríguez L, Palenzuela JA. J. Org. Chem. 2003; 68: 7845
• 15a The Chemistry of Ketenes, Allenes and Related Compounds, Part 1 and 2. Patai S. Wiley; Chichester: 1980
• 15b The Chemistry of Allenes, Vol. I–III. Landor SR. Academic Press; London: 1982
• 15c Hopf H. The Chemistry of Allenes, Vol. II, Chap. 5.7. Landor SR. Academic Press; London: 1982: 563
• 16 Hopf H, Markopoulos G. Beilstein J. Org. Chem. 2012; 8: 1936
• 17a Cycloadditions in Organic Synthesis . Kobayashi S, Jørgensen KA. Wiley-VCH; Weinheim: 2002
• 17b Murakami M, Matsuda T. Cycloadditions of Allenes . In Modern Allene Chemistry, Vol. I and II, Chap. 12. Krause N, Hashmi AS. K. Wiley-VCH; Weinheim: 2004: 760-810
• 17c Yu S, Ma S. Angew. Chem. Int. Ed. 2012; 51: 3074
• 17d Afonso MM, Palenzuela JA. Curr. Org. Chem. 2019; 23: 3004
• 18 Jones ER. H, Lee HH, Whiting MC. J. Chem. Soc. 1960; 341
• 19a Grimaldi J, Bertrand M. Bull. Soc. Chim. Fr. 1971; 947
• 19b Bertrand M. C. R. Hebd. Seances Acad. Sci. 1958; 247: 824
• 20a Ruitenberg K, Kleijn H, Elsevier CJ, Meijer J, Vermeer P. Tetrahedron Lett. 1981; 22: 1451
• 20b Pasto DJ, Kong W. J. Org. Chem. 1989; 54: 4028
• 21 Schneider R, Siegel H, Hopf H. Liebigs Ann. Chem. 1981; 1812
• 22a Hopf H, Siegel H, Germer A, Binger P. Chem. Ber. 1978; 111: 3112
• 22b Murakami M, Ubukata M, Itami K, Ito Y. Angew. Chem. Int. Ed. 1998; 37: 2248
• 22c Murakami M, Minamida R, Itami K, Sawamura M, Ito Y. Chem. Commun. 2000; 2293
• 22d Lee PH, Lee K. Angew. Chem. Int. Ed. 2005; 44: 3253
• 22e Lee PH, Lee K, Kang Y. J. Am. Chem. Soc. 2006; 128: 1139
• 23 Traetteberg M, Bakken P, Hopf H. Acta Chem. Scand., Ser. A 1980; 34: 461
• 24 Klaeboe P, Torgrimson T, Christernsen DH, Hopf H, Eriksson A, Hagen G, Cyvin SJ. Spectrochim. Acta, Part A 1974; 30: 1527
• 25 Bischof P, Gleiter R, Hopf H, Lenich FT. J. Am. Chem. Soc. 1975; 97: 5467
• 26a Lefèvre F, Martin ML, Le Bail H, Odiot S. Org. Magn. Reson. 1975; 7: 315
• 26b Runge W, Kosbahn W. Ber. Bunsenges. Phys. Chem. 1976; 80: 1330
• 27 Bond D. J. Org. Chem. 1990; 55: 661
• 28 Bross H, Schneider R, Hopf H. Tetrahedron Lett. 1979; 2129
• 29 Ferreiro ML, Rodriguez-Otero J, Cabaleiro-Lago EM. Struct. Chem. 2004; 15: 323
• 30 Sakai S. J. Phys. Chem. A 2006; 110: 9443
• 31 Mackay EG, Newton CG, Toombs-Ruane H, Lindeboom EJ, Fallon T, Willis AC, Paddon-Row MN, Sherburn MS. J. Am. Chem. Soc. 2015; 137: 14653
• 32 Banert K, Hagedorn M, Müller A. Eur. J. Org. Chem. 2001; 1089
• 33 Spino C, Thibault C, Gingras S. J. Org. Chem. 1998; 63: 5283
• 34a Woodward RB, Hoffmann R. J. Am. Chem. Soc. 1965; 87: 4388
• 34b Salem L. J. Am. Chem. Soc. 1968; 90: 553
• 34c Houk KN. Tetrahedron Lett. 1970; 2621
• 35 Bertrand M, Grimaldi J, Waegell B. Chem. Commun. 1968; 1141
• 36 Bertrand M, Grimaldi J, Waegell B. Bull. Soc. Chim. Fr. 1971; 962
• 37 Reich HJ, Eisenhart EK, Whipple WL, Kelly MJ. J. Am. Chem. Soc. 1988; 110: 6432
• 38 Maurer H, Hopf H. Eur. J. Org. Chem. 2005; 2702
• 39 Bailey WF, Wachter-Jurcsak NM, Pineau MR, Ovaska TV, Warren RR, Lewus CE. J. Org. Chem. 1996; 61: 8216
• 40 Wang H, Luo H, Zhang Z.-M, Zheng W.-F, Yin Y, Qian H, Zhang J, Ma S. J. Am. Chem. Soc. 2020; 142: 9763
• 41 Teng S, Jiao Z, Chi YR, Zhou JSt. Angew. Chem. Int. Ed. 2020; 59: 2246
• 42 Murakami M, Itami K, Ito Y. J. Am. Chem. Soc. 1997; 119: 7163
• 43 Wilkerson-Hill SM, Lavados CM, Sarpong R. Tetrahedron 2016; 72: 3635
• 44 Choi S, Hwang H, Lee PH. Eur. J. Org. Chem. 2011; 1351
• 45 Hopf H. Angew. Chem., Int. Ed. Engl. 1970; 9: 732
• 46 Hopf H, Böhm I, Kleinschroth J. Org. Synth. 1981; 60: 41
• 47 Skattebøl L. Tetrahedron 1967; 23: 1107
• 48a Wang Z. Comprehensive Organic Name Reactions and Reagents. J. Wiley and Sons; Chichester: 2010
• 48b This reaction is also referred to as the Doering–LaFlamme allene synthesis, see: Doering W. vonE, LaFlamme PM. Tetrahedron 1958; 2: 75
• 49 Sigman MS, Eaton BE. J. Am. Chem. Soc. 1996; 118: 11783
• 50a Farley ED, Marvel CS. J. Am. Chem. Soc. 1936; 58: 29
• 50b Iida K, Hirama M. J. Am. Chem. Soc. 1994; 116: 10310
• 50c Viola A, Collins JJ, Filipp N. Tetrahedron 1981; 37: 3765
• 51 Huntsman WD, Wristers HJ. J. Am. Chem. Soc. 1963; 85: 3308
• 52a Powell DL, Klaeboe P, Christensen D, Hopf H. Spectrochim. Acta, Part A 1973; 29: 7
• 52b Eriksson A, Brunvoll J, Hagen G, Cyvin SJ, Bjøseth A, Powell DL. Acta Chem. Scand., Ser. A 1974; 28: 439
• 53 Traetteberg M, Paulen G, Hopf H. Acta Chem. Scand. 1973; 27: 2227
• 54 Pedersen B, Schaug J, Hopf H. Acta Chem. Scand., Ser. A 1974; 28: 846
• 55 Bieri G, Burger F, Heilbronner E, Maier JP. Helv. Chim. Acta 1977; 60: 2213
• 56 Yu H, Lee OH. J. Org. Chem. 2008; 73: 5183
• 57 Pasto DJ, Yang SH. J. Org. Chem. 1989; 54: 3978
• 58a Hopf H. Angew. Chem., Int. Ed. Engl. 1972; 11: 419
• 58b Hopf H, Lenich FTh. Chem. Ber. 1974; 107: 1891
• 58c Böhm I, Herrmann H, Menke K, Hopf H. Chem. Ber. 1978; 111: 923
• 59 Trahanovsky WS, Lorimor SP. J. Org. Chem. 2006; 71: 1784
• 60 Dix I, Hopf H, Satianarayana TB. N, Ernst L. Beilstein J. Org. Chem. 2010; 6: 932
• 61 Hopf H. In Modern Cyclophane Chemistry, Chap. 7. Gleiter R, Hopf H. Wiley-VCH; Weinheim: 2004: 189-210
• 62a Blickle P, Hopf H. Tetrahedron Lett. 1978; 449
• 62b Delas C, Urabe H, Sato F. Tetrahedron Lett. 2001; 42: 4147
• 63 Mebane RC, Schuster GB. J. Org. Chem. 1983; 48: 810
• 64 Heldeweg RF, Hogeveen H. J. Org. Chem. 1978; 43: 1916
• 65 Kanemasa S, Sakoh H, Wada E, Tsuge O. Bull. Chem. Soc. Jpn. 1986; 59: 1869
• 66a Hopf H, Sherburn M. Angew. Chem. Int. Ed. 2012; 51: 2298
• 66b Newton CG, Sherburn MS. In Cross Conjugation: Modern Dendralene, Radialene and Fulvene Chemistry . Hopf H, Sherburn MS. Wiley-VCH; Weinheim: 2016: 413-444
• 67a Lehrich F, Hopf H. Tetrahedron Lett. 1987; 28: 2697
• 67b Lehrich F, Hopf H, Grunenberg J. Eur. J. Org. Chem. 2011; 2705
• 68 Cergol KM, Newton CG, Lawrence AL, Willis AC, Paddon-Row MN, Sherburn MS. Angew. Chem. Int. Ed. 2011; 50: 10425
• 69 Newton CG, Drew SL, Lawrence AL, Willis AC, Paddon-Row MN, Sherburn MS. Nat. Chem. 2015; 7: 82
• 70 Elgindy C, Ward JS, Sherburn MS. Angew. Chem. Int. Ed. 2019; 58: 14573
• 71a Pledger HJr. J. Org. Chem. 1960; 25: 278
• 71b Dai S.-H, Dolbier WR. Jr. J. Am. Chem. Soc. 1972; 94: 3946
• 72 Pasto DJ. Tetrahedron Lett. 1980; 21: 4787
• 73a For a comprehensive summary of allenic dienophiles, see: Matsuda MT. In Modern Allene Chemistry, Chap. 12. Krause N, Hashmi AS. K. Wiley-VCH; Weinheim: 2004: 727-815
• 73b For allenic phosphonates: Sajna KV, Kotikalapudi R, Chakravaty M, Kumar NN. B, Swamy KC. K. J. Org. Chem. 2011; 76: 920
• 73c For allenic esters, see: Ishikura M, Uchiyama H, Hino A, Katagiri N. J. Heterocycl. Chem. 2001; 38: 675
• 74a Hoffmann HM. R, Ismail ZM. Tetrahedron Lett. 1981; 22: 1953
• 74b Ismail ZM, Hoffmann HM. R. J. Org. Chem. 1981; 46: 3549
• 75 Ishar MP. S, Wali A, Gandhi RP. J. Chem. Soc., Perkin Trans. 1 1990; 2185
• 76a Wittig G, Fritze P. Angew. Chem. 1966; 78: 805
• 76b Wittig G, Fritze P. Justus Liebigs Ann. Chem. 1968; 711: 82
• 76c Yildiz YK, Ozturk T, Balci M. Tetrahedron 1999; 55: 9317
• 76d Ogawa K, Okazaki T, Kinoshita T. J. Org. Chem. 2003; 68: 1579
• 76e Hioki Y, Mori A, Okano K. Tetrahedron 2020; 76: 131103
• 77a Himeshima Y, Sonoda T, Kobayashi H. Chem. Lett. 1983; 12: 1211
• 77b Review: Shi J, Li L, Li Y. Chem. Rev. 2021; 121: 3892
• 78a Barber JS, Styduhar ED, Pham HV, McMahon TC, Houk KN, Garg NK. J. Am. Chem. Soc. 2016; 138: 2512
• 78b Lofstrand VA, West FG. Chem. Eur. J. 2016; 22: 10763
• 78c Inoue K, Nakura R, Okano K, Mori A. Eur. J. Org. Chem. 2018; 3343
• 78d Nakura R, Inoue K, Okano K, Mori A. Synthesis 2019; 51: 1561
• 78e Lofstrand VA, McIntosh KC, Almehmadi YA, West FG. Org. Lett. 2019; 21: 6231
• 78f McVeigh MS, Kelleghan AV, Yamano MM, Knapp RR, Garg NK. Org. Lett. 2020; 22: 4500
• 79 Barber JS, Yamano MM, Ramirez M, Darzi ER, Knapp RR, Liu F, Houk KN, Garg NK. Nat. Chem. 2018; 10: 953
• 80 Yamano MM, Knapp RR, Ngamnithiporn A, Ramirez M, Houk KN, Stoltz BM, Garg NK. Angew. Chem. Int. Ed. 2019; 58: 5653
• 81 Ramirez M, Svatunek D, Liu F, Garg NK, Houk KN. Angew. Chem. Int. Ed. 2021; 60: 14989
• 82 Saxton HM, Sutherland JK, Whaley C. J. Chem. Soc., Chem. Commun. 1987; 1449
• 83 Yoshida M, Hiromatsu M, Kanematsu K. J. Chem. Soc., Chem. Commun. 1986; 1168
• 84a Himbert G, Fink D. Tetrahedron Lett. 1985; 26: 4363
• 84b Himbert G, Henn L. Angew. Chem. 1982; 94: 631
• 84c Diehl K, Himbert G. Chem. Ber. 1986; 119: 3812
• 85a Lam JK, Schmidt Y, Vanderwal CD. Org. Lett. 2012; 14: 5566
• 85b Schmidt Y, Lam JK, Pham HV, Houk KN, Vanderwal CD. J. Am. Chem. Soc. 2013; 135: 7339
• 86a Cheng G, He X, Tian L, Chen J, Li C, Jia X, Li J. J. Org. Chem. 2015; 80: 11100
• 86b Hari DP, Pisella G, Wodrich MD, Tsymbal AV, Tirani FF, Scopelliti R, Waser J. Angew. Chem. Int. Ed. 2021; 60: 5475
• 87 Arylallenes react as Diels–Alder dienes in intramolecular processes with Lewis acid activated dienophiles: Yu P, Li W, Houk KN. J. Org. Chem. 2017; 82: 6398
• 88 Appendino G, Hoflack J, De Clercq PJ. Tetrahedron 1988; 44: 4605
• 89a Hayakawa K, Aso K, Shiro M, Kanematsu K. J. Am. Chem. Soc. 1989; 111: 5312
• 89b For a related, LAu⁺ catalyzed process, see: Sun N, Xie X, Chen H, Liu Y. Chem. Eur. J. 2016; 22: 14175
• 90a Sakai T, Danheiser RL. J. Am. Chem. Soc. 2010; 132: 13203
• 90b Lan Y, Danheiser RL, Houk KN. J. Org. Chem. 2012; 77: 1533
• 90c Bartko SG, Hamzik PJ, Espindola L, Gomez C, Danheiser RL. J. Org. Chem. 2020; 85: 548
• 91 Okamura WH, Curtin ML. Synlett 1990; 1
• 92a Shen R, Huang X. Org. Lett. 2008; 10: 3283
• 92b Shen R, Chen L, Huang X. Adv. Synth. Catal. 2009; 351: 2833
• 92c Zhou H, Zhu D, Xie Y, Huang H, Wang K. J. Org. Chem. 2010; 75: 2706
• 92d Zhou H, Xing Y, Yao Y. Org. Lett. 2010; 12: 3674
• 93 Review: Tius MA. In Science of Synthesis, Vol. 44. Krause N. Thieme Verlag; Stuttgart: 2008: 353
• 94a Deutsch EA, Snider BB. J. Org. Chem. 1982; 47: 2682
• 94b Deutsch EA, Snider BB. Tetrahedron Lett. 1983; 24: 3701
• 94c For a related example with an unactivated dienophile, see: Lemière G, Gandon V, Cariou K, Hours A, Fukuyama T, Dhimane A.-L, Fensterbank L, Malacria M. J. Am. Chem. Soc. 2009; 131: 2993
• 95 Keck GE, Kachensky DF. J. Org. Chem. 1986; 51: 2487

For related examples of this process in total synthesis, see:
• 96a Reich HJ, Eisenhart EK, Olson RE, Kelly MJ. J. Am. Chem. Soc. 1986; 108: 7791
• 96b Gibbs RA, Okamura WH. J. Am. Chem. Soc. 1988; 110: 4062
• 96c Gibbs RA, Bartels K, Lee RW. K, Okamura WH. J. Am. Chem. Soc. 1989; 111: 3717
• 97 Dulcère P, Agati V, Faure R. J. Chem. Soc., Chem. Commun. 1993; 270
• 98 Ma S, Gu Z. Chem. Eur. J. 2008; 14: 2453
• 99 González I, Pla-Quintana A, Roglans A, Dachs A, Solà M, Parcella T, Farjas J, Roura P, Lloveras V, Vidal-Gancedo J. Chem. Commun. 2010; 46: 2944
• 100 Eisenhuth L, Hopf H. J. Am. Chem. Soc. 1974; 96: 5667
• 101 Li W, Zhou L, Zhang J. Chem. Eur. J. 2016; 22: 1558

These processes take place under thermal, photochemical, metal-induced, and base-catalyzed conditions. Thermal hexadehydro-Diels–Alder processes proceed through stepwise mechanisms:
• 102a Liang Y, Hong X, Yu P, Houk KN. Org. Lett. 2014; 16: 5702
• 102b Wang T, Niu D, Hoye TR. J. Am. Chem. Soc. 2016; 138: 7832
• 103a Kocis LS, Brummond KM. Org. Lett. 2014; 16: 4158
• 103b Kocsis LS, Kagalwasa HN, Mutto Sh, Godugu B, Bernhard S, Tantillo DJ, Brummond KM. J. Org. Chem. 2015; 80: 11686
• 104a Bradley AZ, Johnson RP. J. Am. Chem. Soc. 1997; 119: 9917
• 104b Miyakawi K, Suzuki R, Kawano T, Ueda I. Tetrahedron Lett. 1997; 38: 3943
• 105 Hoye TR, Baire B, Niu D, Willoughby PH, Woods BP. Nature 2012; 490: 208
• 106 Wang T, Reddy Naredla R, Thompson SK, Hoye TR. Nature 2016; 532: 484
• 107 Quintana I, Peña D, Pérez D, Guitián E. Eur. J. Org. Chem. 2009; 5519
• 108a Christl M, Braun M, Mueller G. Angew. Chem., Int. Ed. Engl. 1992; 31: 473
• 108b Janoschek R. Angew. Chem., Int. Ed. Engl. 1992; 31: 476
• 108c Hopf H, Berger H, Zimmermann G, Nüchter U, Jones PG, Dix I. Angew. Chem., Int. Ed. Engl. 1997; 36: 1187
• 108d Christl M, Groetsch S. Eur. J. Org. Chem. 2000; 1871
• 109a Hopf H, Musso H. Angew. Chem., Int. Ed. Engl. 1969; 8: 680
• 109b Review: Zimmmermann G. Eur. J. Org. Chem. 2001; 457
• 110 Michael A, Bucher JE. Ber. Dtsch. Chem. Ges. 1895; 28: 2511
• 111a Shibata T, Fujiwara R, Takano D. Synlett 2005; 2062
• 111b Robinson JM, Sakai T, Okano K, Kitawaki T, Danheiser RL. J. Am. Chem. Soc. 2010; 132: 11039
• 112 Prall M, Krüger A, Schreiner PR, Hopf H. Chem. Eur. J. 2001; 7: 4386
• 113 Kobayashi S, Wakumoto S, Yamaguchi Y, Wakayima T, Sugimoto K, Matsubara Y, Yoshida Z. Tetrahedron Lett. 2003; 44: 1807
• 114 An oligonucleotide-linked, piperidine-based cyclic allene was recently generated in an aqueous environment. The azacyclic allene was shown to be water and DNA-compatible, reacting in a strain-activated Diels–Alder reaction with pyrrolidine to generate DNA-encoded libraries: Westphal MV, Hudson L, Mason JW, Pradeilles JA, Zecri FJ, Briner K, Schreiber SL. J. Am. Chem. Soc. 2020; 142: 7776