Two-Step Synthesis of (Z)-3-Aryl-5-(arylmethylidene)butenolides by an Ivanov Reaction/Silver(I)-Catalyzed Lactonization/In Situ Dehydration Sequence

Dedicated to Professor Dieter Enders (RWTH Aachen) on the occasion of his 70^th birthday

Abstract

A stereoselective synthesis of the title compounds was developed. Hexane- and amine-free THF solutions of α-lithiated lithium arylacetates (‘arylacetic acid dianions’) were aldol-added to 3-arylpropynals. This gave 2,5-diaryl-3-hydroxypent-4-ynoic acids with up to a 72:28 preference for the anti-diastereomer (27 examples + 1 exception). When treated with Ag₂CO₃ (1–20 mol%) in DMF at room temperature for 2.5 days, the respective mixtures underwent regio- and stereoselective lactonizations followed by an in situ dehydration. Thereby 3-aryl-5-(arylmethylidene)butenolides were obtained with a Z-configuration of the oxygenated C=C bond. Their overall yields ranged from 46% to 83% (1 exception: 28%). Three 3-aryl-5-(arylmethyli­dene)butenolides contained a C–Br and/or a C–I bond. They allowed a subsequent Pd-catalyzed C–C coupling, which furnished follow-up butenolides.

Key words

aldol addition - cyclization - β-elimination - lactones - silver carbonate - stereoselectivity - tandem reaction

• References

• 1 New address: Carbogen-Amcis AG, Schachenallee 29, 5001 Aarau, Switzerland.
• 2a Ochroleucin A2: Sontag B, Rueth M, Spiteller P, Arnold N, Steglich W, Reichert M, Bringmann G. Eur. J. Org. Chem. 2006; 1023
• 2b Metabolite from of Paxillus involutus: Mikolajczyk L, Antkowiak WZ. Heterocycles 2009; 79: 423
• 3 Spiegel A. Justus Liebigs Ann. Chem. 1883; 219: 3
• 4 Wikholm RJ, Moore HW. J. Am. Chem. Soc. 1972; 94: 6152
• 5 Rao YS, Filler R. Tetrahedron Lett. 1975; 1457
• 6 Rossi R, Bellina F, Mannina L. Tetrahedron Lett. 1998; 39: 3017
• 7 Nakae Y, Manabe A, Miyamoto T. Patent WO2014/129612 A1, 2014 ; (paragraph 59 therein).
• 8a Weibel J.-M, Blanc A, Pale P. Chem. Rev. 2008; 108: 3149

Related reviews:
• 8b Álvarez-Corral M, Muñoz-Dorado M, Rodríguez-García I. Chem. Rev. 2008; 108: 3174
• 8c Silver in Organic Synthesis . Harmata M. Wiley; New York: 2010

Illustrative C–O bond forming cyclizations of alk-2-en-4-ynoic acids cis-5a or alk-4-ynoic acids 5b, which were induced by complexes and/or salts of the following metals: Hg:
• 9a Krafft GA, Katzenellenbogen JA. J. Am. Chem. Soc. 1981; 103: 5459
• 9b Yamamoto M. J. Chem. Soc., Perkin Trans. 1 1981; 582

Pd:
• 9c Lambert C, Utimoto K, Nozaki H. Tetrahedron Lett. 1984; 25: 5323
• 9d Yanagihara N, Lambert C, Iritani K, Utimoto K, Nozaki H. J. Am. Chem. Soc. 1986; 108: 2753
• 9e Arcadi A, Burini A, Cacchi S, Delmastro M, Marinelli F, Pietroni BR. J. Org. Chem. 1992; 57: 976
• 9f Wakabayashi T, Ishii Y, Ishikawa K, Hidai M. Angew. Chem., Int. Ed. Engl. 1996; 35: 2123 ; Angew. Chem. 1996, 108, 2268
• 9g Mori H, Kubo H, Hara H, Katsumura S. Tetrahedron Lett. 1997; 38: 5311
• 9h Ref. 6.
• 9i Wang Y.-G, Wachi M, Kobayashi Y. Synlett 2006; 481
• 9j Han X, Jiang L, Tang M, Hu W. Org. Biomol. Chem. 2011; 9: 3839
• 9k Ogata K, Sasano D, Yokoi T, Isozaki K, Seike H, Takaya H, Nakamura M. Chem. Lett. 2012; 41: 498
• 9l Nebra N, Monot J, Shaw R, Martin-Vaca B, Bourissou D. ACS Catal. 2013; 3: 2930
• 9m Nagendiran A, Verho O, Haller C, Johnston EV, Bäckvall JE. J. Org. Chem. 2014; 79: 1399

Ag:
• 9n Clemo NG, Pattenden G. J. Chem. Soc., Perkin Trans. 1 1986; 2133
• 9o Pale P, Chuche J. Tetrahedron Lett. 1987; 28: 6447
• 9p Dalla V, Pale P. Tetrahedron Lett. 1994; 35: 3525
• 9q Ogawa Y, Maruno M, Wakamatsu T. Heterocycles 1995; 41: 2587
• 9r Xu C, Negishi E.i. Tetrahedron Lett 1999; 40: 431
• 9s Rossi R, Bellina F, Catanese A, Mannina L, Valensin D. Tetrahedron 2000; 56: 479
• 9t Bellina F, Ciucci D, Vergamini P, Rossi R. Tetrahedron 2000; 56: 2533
• 9u Anastasia L, Xu C, Negishi E. Tetrahedron Lett. 2002; 43: 5673
• 9v Yoshikawa T, Shindo M. Org. Lett. 2009; 11: 5378
• 9w Šenel P, Tichotová L, Votruba I, Buchta V, Špulák M, Kuneš J, Nobilis M, Krenk O, Pour M. Bioorg. Med. Chem. 2010; 18: 1988

Rh:
• 9x Chan DM. T, Marder TB, Milstein D, Taylor NJ. J. Am. Chem. Soc. 1987; 109: 6385
• 9y Elgafi S, Field LD, Messerle BA. J. Organomet. Chem. 2000; 607: 97

Zn:
• 9z Ref. 9u.

Au:
• 9aa Harkat H, Weibel J.-M, Pale P. Tetrahedron Lett. 2006; 47: 6273
• 9ab Toullec PY, Genin E, Antoniotti S, Genêt J.-P, Michelet V. Synlett 2008; 707
• 9ac Harkat H, Dembelé AY, Weibel JM, Blanc A, Pale P. Tetrahedron 2009; 65: 1871
• 9ad Tomás-Mendivil E, Toullec PY, Díez J, Conejero S, Michelet V, Cadierno V. Org. Lett. 2012; 14: 2520
• 9ae Lee L.-C, Zhao Y. J. Am. Chem. Soc. 2014; 136: 5579
• 9af Rodríguez-Álvarez MJ, Vidal C, Díez J, García-Álvarez J. Chem. Commun. 2014; 50: 12927
• 9ag Shu X.-Z, Nguyen SC, He Y, Oba F, Zhang Q, Canlas C, Somorjai GA, Alivisatos AP, Toste FD. J. Am. Chem. Soc. 2015; 137: 7083
• 9ah Eriksson K, Verho O, Nyholm L, Oscarsson S, Bäckvall J.-E. Eur. J. Org. Chem. 2015; 2250

Cu:
• 9ai Sun C, Fang Y, Li S, Zhang Y, Zhao Q, Zhu S, Li C. Org. Lett. 2009; 11: 4084
• 9aj Petrignet J, Ngi SI, Abarbi M, Thibonnet J. Tetrahedron Lett. 2014; 55: 982

Pt:
• 9ak Alemán J, del Solar V, Navarro-Ranninger C. Chem. Commun. 2010; 46: 454

Examples of acid- or base-triggered C–O bond-forming cyclizations of alk-2-en-4-ynoic acids cis-5a:
• 10a Ref. 5.
• 10b Uchiyama M, Ozawa H, Takuma K, Matsumoto Y, Yonehara M, Hiroya K, Sakamoto T. Org. Lett. 2006; 8: 5517

For example, induced by Pd:
• 11a Ref. 9f.
• 11b Nebra N, Monot J, Shaw R, Martin-Vaca B, Bourissou D. ACS Catal. 2013; 3: 2930

By Ag:
• 11c Ogawa Y, Maruno M, Wakamatsu T. Heterocycles 1995; 41: 2587
• 11d Ref. 9t.
• 11e Ref. 9u.

By Rh:
• 11f Ref. 9x.
• 11g Man BY. W, Knuhtsen A, Page MJ, Messerle BA. Polyhedron 2013; 61: 248

For example, induced by Hg:
• 12a Jong T.-T, Williard PG, Porwoll JP. J. Org. Chem. 1984; 49: 735

By Pd:
• 12b Ref. 6.
• 12c Sashida H. Synthesis 1999; 1145
• 12d Nebra N, Monot J, Shaw R, Martin-Vaca B, Bourissou D. ACS Catal. 2013; 3: 2930
• 12e Wang H, Han X, Lu X. Tetrahedron 2013; 69: 8626

By Ag:
• 12f Ref. 9t.
• 12g Rammah MM, Othman M, Ciamala K, Strohmann C, Rammah MB. Tetrahedron 2008; 64: 3505

By Rh:
• 12h Ref. 11g.

By Au:
• 12i Marchal E, Uriac P, Legouin B, Toupet L, van der Weghe P. Tetrahedron 2007; 63: 9979
• 12j Hashmi AS. K, Lothschütz C, Döpp R, Ackermann M, De Buck Becker J, Rudolph M, Scholz C, Rominger F. Adv. Synth. Catal. 2012; 354: 133
• 12k Zhu Y, Yu B. Chem. Eur. J. 2015; 21: 8771

By Au/Ag:
• 12l Asao N, Aikawa H, Tago S, Umetsu K. Org. Lett. 2007; 9: 4299
• 12m Aikawa H, Tago S, Umetsu K, Haginiwa N, Asao N. Tetrahedron 2009; 65: 1774
• 12n Jean M, Renault J, van de Weghe P, Asao N. Tetrahedron Lett. 2010; 51: 378
• 13a Original communication on ‘Rules for Ring Closure’: Baldwin JE. J. Chem. Soc., Chem. Commun. 1976; 734
• 13b Review ‘Stereoelectronic Effects in the Formation of 5- and 6-Membered Rings: The Role of Baldwin’s Rules’: Johnson CD. Acc. Chem. Res. 1993; 26: 476

Modifications, ‘Cyclizations of Alkynes: Revisiting Baldwin’s Rules for Ring Closure’:
• 13c Gilmore K, Alabugin IV. Chem. Rev. 2011; 111: 6513
• 13d ‘Finding the right path: Baldwin ‘Rules for Ring Closure’ and Stereoelectronic Control of Cyclizations’: Alabugin IV. Chem. Commun. 2013; 49: 11246
• 14a Both reaction modes were assessed ‘favored’ in the original formulation of Baldwin’s ring-closure rules (ref. 13a). This assessment was not altered in refined formulations for dig cyclizations (refs. 13c,d). Calculations quantified these assessments: The pent-4-yn-1-olate anion prefers a 5-exo-dig cyclization (E _a = 13.4 kcal/mol) over the 6-endo-dig cyclization (E _a = 19.6 kcal/mol) by as much as ΔE _a = 6.2 kcal/mol.
• 14b Alabugin IV, Gilmore K, Manoharan M. J. Am. Chem. Soc. 2011; 133: 12608

For example:
• 15a In DMF, (E)-3-ethoxy-2-methyl-5-phenylpent-2-en-4-ynoic acid and 10 mol% Ag₂CO₃ reacted giving a >95.5 mixture of (Z)-5-benzylidene-4-ethoxy-3-methylbutenolide and 4-ethoxy-6-phenyl-3-methylpyran-2-one whereas 10 mol% AgSbF₆ furnished the same lactones as a 9:91 mixture (ref. 9v).
• 15b Also in DMF, (Z)-undec-2-en-4-ynoic acid and 5 mol% Ag₂CO₃ gave a 96.4 ratio of (Z)-5-heptylidenebutenolide and 4-hexylpyran-2-one while 5 mol% AgBF₄ delivered the same lactones as a 12:88 mixture (ref. 9u).

For example:
• 16a Ref. 12a.
• 16b Dalla V, Pale P. Tetrahedron Lett. 1994; 35: 3525
• 16c Haga Y, Okazaki M, Shuto Y. Biosci. Biotechnol. Biochem. 2003; 67: 2183
• 16d Ref. 9j.
• 16e See also Scheme 14.
• 17 Experimental description: Bugarin A, Connell BT. Tetrahedron Lett. 2015; 56: 3285 ; (‘Supplementary data’, compound S-2)
• 18 Sonogashira K, Tohda Y, Hagihara N. Tetrahedron Lett. 1975; 4467
• 19 Experimental description: Su Q, Yan H, Gao S.-C, Xie D.-X, Cai Q.-Y, Shao G, Peng Z.-H, An D.-L. Synth. Commun. 2013; 43: 2648

Reviews:
• 20a Thompson CM, Green DL. C. Tetrahedron 1991; 47: 4223
• 20b Thompson CM In Dianion Chemistry in Organic Synthesis . Thompson CM. CRC Press; Boca Raton: 1994: 88-129
• 20c Gil S, Parra M. Recent Res. Dev. Org. Chem. 2002; 6: 449
• 21a Ivanoff D, Spassoff A. Bull. Soc. Chim. Fr. 1931; 49: 19
• 21b Ivanoff D, Spassoff A. Bull. Soc. Chim. Fr. 1931; 49: 375
• 21c See also: Blagoev B, Ivanov D. Synthesis 1970; 615
• 22a Ivanov D, Vassilev G, Panayotov I. Synthesis 1975; 83
• 22b Ref. 20.
• 22c Brun EM, Casades I, Gil S, Mestres R, Parra M. Tetrahedron Lett. 1998; 39: 5443
• 22d Parra M, Sotoca E, Gil S. Eur. J. Org. Chem. 2003; 1386
• 23a Seebach D. Angew. Chem., Int. Ed. Engl. 1988; 27: 1624 ; Angew. Chem. 1988, 100, 1685
• 23b Braun M. Modern Enolate Chemistry . Wiley-VCH; Weinheim: 2016: 83-97
• 24 Streitwieser A, Husemann M, Kim Y.-K. J. Org. Chem. 2003; 68: 7937
• 25 Mulzer J, Zippel M, Brüntrup G, Segner J, Finke J. Liebigs Ann. Chem. 1980; 1108. These researchers removed diisopropylamine and hexane from aliphatic lithium carboxylate enolates before engaging them in Ivanov reactions. In contrast, they employed the lithium phenylacetate enolate in the presence diisopropylamine and hexane. From this, we concluded that removal of diisopropylamine and hexane from the lithium arylacetate enolates would rather enhance than diminish their reactivities. This is why we proceeded such as we did
• 26 In contrast, a beneficial effect of a combined amine/amide-containing constituent of mixed aggregates derived from α-lithiated lithium arylacetates was reported by: Ma Y, Stivala CE, Wright AM, Hayton T, Liang J, Keresztes I, Lobkovsky E, Collum DB, Zakarian A. J. Am. Chem. Soc. 2013; 135: 16853
• 27 Still WC, Kahn M, Mitra A. J. Org. Chem. 1978; 43: 2923
• 28a Mukhopadhyay T, Seebach D. Helv. Chim. Acta 1982; 65: 385
• 28b Braun M. Modern Enolate Chemistry . Wiley-VCH; Weinheim: 2016: 11-50
• 29a The configuration of the major diastereomers of the Ivanov adducts contained in Scheme 5 and Scheme 10 equals the configuration of the dominating Ivanov adduct from magnesium phenylacetate enolate and benzaldehyde: Zimmerman HE, Traxler MD. J. Am. Chem. Soc. 1957; 79: 1920 . This study explained the preferential formation of that diastereomer by what became known as the Zimmerman–Traxler model
• 29b The configuration of the major diastereomers of the Ivanov adducts contained in Scheme 5 and Scheme 10 equals the configuration of the dominating Ivanov adducts obtained under kinetic control very generally from α-arylated or α-alkylated lithium actate enolates and aromatic as well as aliphatic aldehydes (ref. 25).
• 29c In CDCl₃ solutions, the methyl ester of Ivanov adduct 12 exhibits ³ J _2-H,_3-H = 9.2 Hz, if configured like the 12-diastereomer depicted in the top line of Table 1 and ³ J _2-H,_3-H = 7.65 Hz, if configured oppositely. This interpreted was calculationally – and found – by: Spassov SL. Tetrahedron 1969; 25: 3631
• 29d Conformational analyses of related 1,2-disubstituted 1,2-diphenylethanes by force-field calculations: Ivanov PM, Pojarlieff IG. J. Mol. Struct. (Theochem) 1988; 170: 257

Method:
• 30a Seyferth D, Menzel H, Dow AW, Flood TC. J. Organomet. Chem. 1972; 44: 279
• 30b Hashimoto N, Aoyama T, Shiori T. Chem. Pharm. Bull. 1981; 29: 1475
• 31 Christl M, Bodenschatz G, Feineis E, Hegmann J, Hüttner G, Mertelmeyer S, Schätzlein K. Liebigs Ann. Chem. 1996; 853

The absolute value of the coupling constant ³ J(¹³C,¹H) in compounds with a trans-configured ¹³C–C=C–¹H motif was never <7.4 Hz in several varieties of compounds studied by
• 32a Anderson JE. Tetrahedron Lett. 1975; 4079
• 32b Vögeli U, von Philipsborn W. Org. Magn. Reson. 1975; 7: 617
• 32c Douglas AW. Org. Magn. Reson. 1977; 9: 69
• 32d Fischer P, Schweizer E, Langner J, Schmidt U. Magn. Reson. Chem. 1994; 32: 567
• 33 The melting points are neither corrected nor uncorrected, as these terms refer to total immersion thermometers. In our laboratory, partial immersion thermometers are used exclusively. By definition these need no correction for immersion depth: Tiers GV. D. J. Chem. Educ. 1990; 67: 258