The Catalytic Alkylative Desymmetrization of Anhydrides in a Formal Synthesis of Ionomycin

Dedicated to Professor Scott Denmark on the occasion of his 65^th birthday.

Published as part of the Special Section dedicated to Scott E. Denmark on the occasion of his 65^th birthday.

Abstract

The catalytic desymmetrization of anhydrides with zinc reagents provides access to deoxypolypropionate and polypropionate synthons. A synthesis of ionomycin was pursued in which three of the four fragments were assembled using this methodology. Two of the strategies (enol silane/oxocarbenium coupling and reductive cyclization) were not successful at installing the C23 stereocenter, but this stereochemical issue was overcome through a reduction/S_N2 approach. In addition to the synthesis of a protected diastereomer of ionomycin, the synthesis of a C17–C32 fragment constitutes a formal total synthesis.

Key words

total synthesis - rhodium - enantioselective synthesis - anhydride desymmetrization - diastereoselectivity

• References

• 1a Cook MJ. Rovis T. J. Am. Chem. Soc. 2007; 129: 9302
• 1b Cook MJ. Rovis T. Synthesis 2009; 335
• 1c Johnson JB. Cook MJ. Rovis T. Tetrahedron 2009; 65: 3202
• 1d Stache EE. Rovis T. Doyle AG. Angew. Chem. Int. Ed. 2017; 56: 3679
• 2 Cochran BM. Henderson DD. Thullen SM. Rovis T. Synlett 2018; 29: 306

For activity and isolation, see:
• 3a Liu C.-m. Hermann TE. J. Biol. Chem. 1978; 253: 5892
• 3b Liu W.-c. Slusarchyk DS. Astle G. Trejo WH. Brown WE. Meyers E. J. Antibiot. 1978; 31: 815

For structure elucidation, see:
• 3c Toeplitz BK. Cohen AI. Funke PT. Parker WL. Gougoutas JZ. J. Am. Chem. Soc. 1979; 101: 3344

Fragment syntheses:
• 4a Hanessian S. Murray PJ. Sahoo SP. Tetrahedron Lett. 1985; 26: 5627
• 4b Hanessian S. Murray PJ. Can. J. Chem. 1986; 64: 2231
• 4c Hanessian S. Murray PJ. Tetrahedron 1987; 43: 5055

Total synthesis:
• 4d Hanessian S. Cooke NG. DeHoff B. Sakito Y. J. Am. Chem. Soc. 1990; 112: 5276

Fragment syntheses:
• 5a Evans DA. Morrissey MM. Dow RL. Tetrahedron Lett. 1985; 26: 6005
• 5b Evans DA. Dow RL. Tetrahedron Lett. 1986; 27: 1007

Total synthesis:
• 5c Evans DA. Dow RL. Shih TL. Takacs JM. Zahler R. J. Am. Chem. Soc. 1990; 112: 5290

Fragment synthesis:
• 6a Lautens M. Chiu P. Colucci JT. Angew. Chem. Int. Ed. 1993; 32: 281

Total synthesis:
• 6b Lautens M. Colucci JT. Hiebert S. Smith ND. Bouchain G. Org. Lett. 2002; 4: 1879

Fragment syntheses:
• 7a Cooksey J. Kocienski P. Li Y.-F. Collect. Czech. Chem. Commun. 2005; 70: 1653
• 7b Cooksey JP. Kocienski PJ. Li Y.-f. Schunk S. Snaddon TN. Org. Biomol. Chem. 2006; 4: 3325
• 7c Li Y. Cooksey JP. Gao Z. Kocienski PJ. McAteer SM. Snaddon TN. Synthesis 2011; 104

Total synthesis:
• 7d Gao Z. Li Y. Cooksey JP. Snaddon TN. Schunk S. Viseux EM. E. McAteer SM. Kocienski PJ. Angew. Chem. Int. Ed. 2009; 48: 5022
• 8a Wuts PG. M. D’Costa R. Butler W. J. Org. Chem. 1984; 49: 2582
• 8b Nicoll-Griffith D. Weiler L. J. Chem. Soc., Chem. Commun. 1984; 659
• 8c Schreiber SL. Wang S. J. Am. Chem. Soc. 1985; 107: 5303
• 8d Spino C. Weiler L. Tetrahedron Lett. 1987; 28: 731
• 8e Shelly KP. Weiler L. Can. J. Chem. 1988; 66: 1359
• 8f Nicoll-Griffith DA. Weiler L. Tetrahedron 1991; 47: 2733
• 8g Taschner MJ. Chen Q.-Z. Bioorg. Med. Chem. Lett. 1991; 1: 535
• 8h Guidon Y. Yoakin C. Gorys V. Ogilvie WW. Delorme D. Renaud J. Robinson G. Lavallée J.-F. Slassi A. Jung G. Rancourt J. Durkin K. Liotta D. J. Org. Chem. 1994; 59: 1166
• 8i Hu TQ. Weiler L. Can. J. Chem. 1994; 72: 1500
• 8j von der Emde H. Langels A. Noltemeyer M. Brüchner R. Tetrahedron Lett. 1994; 35: 7609
• 8k Montaña AM. García F. Grima PM. Tetrahedron 1999; 55: 5483
• 8l Montaña AM. García F. Grima PM. Tetrahedron Lett. 1999; 40: 1375
• 8m Spino C. Allan M. Can. J. Chem. 2004; 82: 177
• 8n Novak T. Tan Z. Liang B. Negishi E.-i. J. Am. Chem. Soc. 2005; 127: 2838
• 8o Marshall JA. Mikowski AM. Org. Lett. 2006; 8: 4375
• 8p Yadav JS. Yadav NN. Reddy BV. S. Tetrhahedron 2015; 71: 7539
• 9 Paterson I. Boddy I. Mason I. Tetrahedron Lett. 1987; 28: 5205

For the synthesis and chemistry of [Rh(nbd)OAc]₂, see:
• 10a Filloux CM. Rovis T. J. Am. Chem. Soc. 2015; 137: 508

For a review on halide influence on metal catalysis, see:
• 10b Fagnou K. Lautens M. Angew. Chem. Int. Ed. 2002; 41: 26
• 11 Under the same conditions using the same zinc reagent 11, the use of [Rh(nbd)Cl]₂ led to 60% conversion and the use of [Rh(nbd)OAc]₂ led to 80% conversion by ¹H NMR analysis of the unpurified reactions (trimethoxybenzene as the internal standard). Additionally, the [Rh(nbd)OAc]₂ produces a cleaner reaction mixture.

The use of catalytic CuI and longer equilibrium times leads to purer dialkylzinc reagent 11. For synthesis of dialkylzinc reagents, see:
• 12a Rozema MJ. Sidduri A. Knochel P. J. Org. Chem. 1992; 57: 1956
• 12b Knochel P. Singer RD. Chem. Rev. 1993; 93: 2117
• 13 A two-step procedure converting the alcohol into an iodide and displacement generates slightly cleaner thiol. See Supporting Information for procedure.
• 14a Marcantoni E. Nobili F. J. Org. Chem. 1997; 62: 4183
• 14b Arjona O. Menchaca R. Plumet J. Org. Lett. 2001; 3: 107
• 15 Brown HC. Dhar RK. Bakshi RK. Pandiarajan PK. Singaram B. J. Am. Chem. Soc. 1989; 111: 3441
• 16 Bartlett SL. Beaudry CM. J. Org. Chem. 2011; 76: 9852
• 17 See reference 7c.
• 18 Evans DA. Hoveyda AH. J. Org. Chem. 1990; 55: 5190
• 19 Nishida A. Hamada T. Yonemitsu O. J. Org. Chem. 1988; 53: 3386
• 20 We unsuccessfully attempted the Julia olefination with the aldehyde at C16 and the sulfone at C17.
• 21 Lewis MD. Cha JK. Kishi Y. J. Am. Chem. Soc. 1982; 104: 4976
• 22 Tokuyama H. Miyazaki T. Yokoshima S. Fukuyama T. Synlett 2003; 1512
• 23 Gierasch TM. Shi Z. Verdine GL. Org. Lett. 2003; 5: 621
• 24a Nicolaou KC. Hwang CK. Nugiel DA. J. Am. Chem. Soc. 1989; 111: 4136
• 24b González IC. Forsyth CJ. J. Am. Chem. Soc. 2000; 122: 9099
• 25 Wilcox CS. Cowart MD. Carbohydr. Res. 1987; 171: 141
• 26 Matsumura K. Hashiguchi S. Ikariya T. Noyori R. J. Am. Chem. Soc. 1997; 119: 8738
• 27 Ogawa K. Koyama Y. Ohashi I. Sato I. Hirama M. Angew. Chem. Int. Ed. 2009; 48: 1110

Observed reduction:
• 28a Kögl M. Brecker L. Warrass R. Mulzer J. Eur. J. Org. Chem. 2008; 2714

Did not observe reduction:
• 28b Swindell CS. Patel BP. Tetrahedron Lett. 1987; 28: 5275
• 28c VanderRoest JM. Grieco PA. J. Am. Chem. Soc. 1993; 115: 5841
• 28d Naidu SV. Kumar P. Tetrahedron Lett. 2007; 48: 2279
• 29a Dreher SD. Hornberger KR. Sarraf ST. Leighton JL. Org. Lett. 2000; 2: 3197
• 29b Bonini C. Campaniello M. Chiummiento L. Videtta V. Tetrahedron 2008; 64: 8766
• 29c Bonini C. Chiummiento L. Funicello M. Lupattelli P. Videtta V. Tetrahedron Lett. 2008; 49: 5455
• 30 Preliminary results show the promise of an oxymercuration route to targeted aldehyde 42 (Scheme 14).