Allenes in Diels–Alder Cycloadditions

Henning Hopf; Michael S. Sherburn

doi:10.1055/s-0040-1706052

Synthesis 2022; 54(04): 864-886
DOI: 10.1055/s-0040-1706052

special topic

Cycloadditions – Established and Novel Trends – in Celebration of the 70th Anniversary of the Nobel Prize Awarded to Otto Diels and Kurt Alder

Allenes in Diels–Alder Cycloadditions

Henning Hopf∗

^aInstitut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany

,

Michael S. Sherburn∗

^bResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia

› Author Affiliations

Abstract

All articles of this category

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

Full Text

References

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