Stereoselective Synthesis of the C13–C28 Subunit of (–)-Laulimalide Utilizing an α-Chlorosulfide Intermediate

Abstract

A stereoselective route to the C13–C28 subunit of (–)-laulimalide is described. l-Tartaric acid is the source of the hydroxy groups at C19 and C20. An α-chlorosulfide is employed as the key intermediate for the creation of the C17–C18 bond and the C16–C17 double bond was introduced using the Mislow–Braverman rearrangement and Hutchin’s dexoxygenation with concomitant double bond transposition reaction. The C15 and C23 stereogenic centers were created using catalytic asymmetric reactions. The trisubstituted and trans-disubstituted alkenes were created stereoselectively by taking advantage of ring-closing metathesis and the Julia–Kocienski olefination reaction, respectively.

Key words

laulimalide - α-chloro sulfide - Julia–Kocienski olefination - Mislow–Braverman rearrangement - ring-closing metathesis

• References and Notes

• 1a Quinoa E, Kakou Y, Crews P. J. Org. Chem. 1988; 53: 3642
• 1b Corley DG, Herb R, Moore RE, Scheuer PJ, Paul VJ. J. Org. Chem. 1988; 53: 3644
• 1c Higa T, Tanaka J.-I, Bernardinelli G, Jefford CW. Chem. Lett. 1996; 255
• 1d Higa T, Tanaka J.-I, Garcia Gravalos D. Int. Patent WO9710242, 1997
• 1e Cutignano A, Bruno I, Bifulco G, Casapullo A, Debitus C, Gomez-Paloma L, Riccio R. Eur. J. Org. Chem. 2001; 775
• 2a Mooberry SL, Tien G, Hernandez AH, Plubrukarn A, Davidson BS. Cancer Res. 1999; 59: 653
• 2b For a review, see: Gallagher BM. Jr. Curr. Med. Chem. 2007; 14: 2959
• 3a Pryor DE, Brate AO, Bilcer G, Diaz JF, Wang YF, Wang Y, Kabaki M, Jung MK, Andreu JM, Ghosh AK, Giannakakou P, Hamel E. Biochemistry 2002; 41: 9109
• 3b Gaitanos TN, Buey RM, Diaz FJ, Northcote PT, Teesdale-Spittle P, Andreu JM, Miller JH. Cancer Res. 2004; 64: 5063
• 3c Hamel E, Day BW, Miller JH, Jung KM, Northcote PT, Ghosh AK, Curran PD, Cushman M, Nicolaou KC, Paterson I, Sorensen EJ. Mol. Pharmacol. 2006; 70: 1555
• 3d Gapud EJ, Bai R, Ghosh AK, Hamel E. Pharmacology 2004; 66: 113

For the total synthesis of 1, see:
• 4a Ghosh AK, Wang Y. J. Am. Chem. Soc. 2000; 122: 11027
• 4b Ghosh AK, Wang Y, Kim JT. J. Org. Chem. 2001; 66: 8973
• 4c Mulzer J, Ohler E. Angew. Chem. Int. Ed. 2001; 40: 3842 ; Angew. Chem. 2001, 113, 3961
• 4d Paterson I, De Savi C, Tudge M. Org. Lett. 2001; 3: 3149
• 4e Mulzer J, Enev VS, Kaehlig H. J. Am. Chem. Soc. 2001; 123: 10764
• 4f Wender PA, Hegde SG, Hubbard RD, Zhang L. J. Am. Chem. Soc. 2002; 124: 4956
• 4g Williams DR, Liang M, Mullins RJ, Stites RE. Tetrahedron Lett. 2002; 43: 4841
• 4h Mulzer J, Ahmed A, Hoegenauer EK, Enev VS, Hanbauer M, Kaehlig H, Ohler E. J. Org. Chem. 2003; 68: 3026
• 4i Crimmins MT, Stanton MG, Allen SP. J. Am. Chem. Soc. 2002; 124: 5958
• 4j Nelson SG, Cheung WS, Kassick AJ, Hilfiker MA. J. Am. Chem. Soc. 2003; 125: 13654
• 4k Gallagher BM, Fang FG. Jr, Johannes CW, Pesant M, Tremblay MR, Zhao H, Akasaka K, Li XY, Liu J, Littlefield BA. Bioorg. Med. Chem. Lett. 2004; 14: 575
• 4l Uenishi J, Ohmi M. Angew. Chem. Int. Ed. 2005; 44: 2756 ; Angew. Chem. 2005, 117, 2816
• 4m For a review, see: Mulzer J, Ohler E. Chem. Rev. 2003; 80: 3753
• 4n Gollner A, Altmann K.-H, Gertsch J, Mulzer J. Chem. Eur. J. 2009; 15: 5979
• 4o Trost BM, Amans D, Seganish WM, Chung CK. J. Am. Chem. Soc. 2009; 131: 17087

For the synthesis of analogues of 1, see:
• 5a Wender PA, Hegde SG, Hubbard RD, Zhang L, Mooberry SL. Org. Lett. 2003; 5: 3507
• 5b Paterson I, Bergmann H, Menche D, Berkessel A. Org. Lett. 2004; 6: 1293
• 5c Mooberry SL, Randall-Hlubek DA, Leal RM, Hegde SG, Hubbard RD, Zhang L, Wender PA. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 8803
• 5d Gallagher BM. Jr, Zhao H, Pesant M, Fang FG. Tetrahedron Lett. 2005; 46: 923
• 5e Paterson I, Menche D, Hakansson AE, Longstaff A, Wong D, Barasoain I, Buey RM, Diaz JF. Bioorg. Med. Chem. Lett. 2005; 15: 2243
• 5f Wender PA, Hilinski MK, Soldermann NG, Mooberry SL. Org. Lett. 2006; 8: 1507
• 5g Wender PA, Hilinski MK, Skaanderup PR, Soldermann NG, Mooberry SL. Org. Lett. 2006; 8: 4105
• 5h Faveau C, Mondon M, Gesson JP, Mahnke T, Gebhardt S, Koert U. Tetrahedron Lett. 2006; 47: 8305
• 6a Blakemore PR, Cole WJ, Kocienski PJ, Morley A. Synlett 1998; 26
• 6b For a review, see: Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002; 2563
• 7 Raghavan S, Kumar VV, Chowhan LR. Synlett 2010; 1807
• 8 Mash EA, Nelson KA, Van Deusen S, Hemperly SB. Org. Synth. 1990; 68: 92
• 9 Nakagawa I, Hata T. Tetrahedron Lett. 1975; 1409
• 10a Omura K, Swern D. Tetrahedron 1978; 34: 1651
• 10b Huang SL, Omura K, Swern D. Synthesis 1978; 297
• 11a Pu L. Tetrahedron 2003; 5: 9873
• 11b Gao G, Xie RG, Pu L. PNAS 2004; 101: 5417
• 12 The enantiomeric ratio was determined by HPLC of the alcohol. CHIRALPAK^®IA-3 [(0.46 cm I.D. × 25 cm L), isocratic hexane, flow rate: 1.0 mL/min, 25 °C]; S-isomer t _R = 12.739 min and R-isomer t _R = 12.946 min. The ‘S’ configuration at the newly created carbinol stereocentre was unambiguously established by comparison of the ¹H NMR spectra of esters of 17 and racemic 17 prepared using (S)-methoxymandelic acid.
• 13a Miller EG, Rayner DR, Mislow K. J. Am. Chem. Soc. 1966; 88: 3139
• 13b Braverman S, Stabinsky Y. Chem. Commun. 1967; 270
• 13c Evans DA, Andrews GC. Acc. Chem. Res. 1974; 7: 147
• 14 Baudin JB, Julia SA, Lorne R. Synlett 1991; 509
• 15 Luche JL. J. Am. Chem. Soc. 1978; 100: 2226
• 16 Myers AG, Zheng B. Tetrahedron Lett. 1996; 28: 4841
• 17 Hutchins RO, Kacher M, Rua L. J. Org. Chem. 1975; 40: 923
• 18 The hydrazone formation and subsequent reductive deoxygenation steps proceeded more efficiently using o-nitrobenzenesulfonyl hydrazine (o-NsNHNH₂) rather than using p-toluenesulfonyl hydrazine (TsNHNH₂). To the best of our knowledge this is the first report on the use of o-nitrobenzenesulfonyl hydrazine for reductive deoxygenation.
• 19 Alonso E, Ramón DJ, Yus M. Tetrahedron 1997; 53: 14355
• 20 Aldehyde 28 was obtained by ozonolysis of the di-OPMB ether of cis-1,4-butenediol. See: Supporting Information for a detailed experimental protocol.
• 21 Keck GE, Tarbet KH, Gwraci LS. J. Am. Chem. Soc. 1993; 115: 8467
• 22 The enantiomeric ratio was determined by HPLC of the alcohol. CYCLOBOND^® [(0.46 cm I.D. × 25 cm L), isocratic 3% MeCN in H₂O, flow rate: 1.0 mL/min, 25 °C]; R-isomer t _R = 9.658 min and S-isomer t _R = 11.153 min.
• 23 Fu GC, Grubbs RH. J. Am. Chem. Soc. 1992; 114: 5426
• 24 Horita K, Yoshioka T, Tanaka T, Oikawa Y, Yonemitsu O. Tetrahedron 1986; 42: 3021
• 25a Mitsunobu O, Yamada Y. Bull. Chem. Soc. Jpn. 1967; 40: 2380
• 25b Mitsunobu O. Synthesis 1981; 1
• 25c Curran DP, Zhang Q, Richard C, Lu H, Gudipati V, Wilcox CS. J. Am. Chem. Soc. 2006; 128: 9561
• 25d Cramer N, Buchweitz M, Laschat S, Frey W, Baro A, Mathieu D, Richter C, Schwalbe H. Chem. Eur. J. 2006; 12: 2488
• 26 Compound 4: To a solution of sulfone 5 (54 mg, 0.17 mmol, 1.5 equiv) in anhyd DMF (0.2 mL) and HMPA (64 μL) cooled at –60 °C was added KHMDS (192 μL, 15% in toluene, 1.2 equiv) via syringe. The reaction was stirred for 15 min and cooled to –78 °C. A solution of aldehyde 6 (80 mg, 0.12 mmol, 1 equiv) in anhyd DMF (0.2 mL) and HMPA (64 μL) was added dropwise. The reaction was stirred at the same temperature for 1 h and allowed to warm to ambient temperature for over a period of 12 h. The reaction mixture was quenched by adding sat. aq NH₄Cl solution (2 mL), the layers were separated and the aqueous layer was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were washed with brine, dried over anhyd Na₂SO₄, filtered and concentrated under reduced pressure to furnish the crude product. Purification of the crude residue via flash chromatography on silica gel using 12% EtOAc–hexane as the eluent afforded 4 as a colorless oil (56 mg, 0.09 mmol) in 75% yield. TLC (SiO₂): R_f 0.6 (EtOAc–hexane, 3:7); [α]²⁵ _D –21° (c = 0.98 in CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.58–7.70 (m, 4 H), 7.24–7.34 (m, 6 H), 5.74 (dt, J = 14.8, 5.0 Hz, 1 H), 5.52–5.64 (m, 2 H), 5.23–5.38 (m, 2 H), 4.56 (d, J = 7.0 Hz, 1 H), 4.37 (d, J = 7.0 Hz, 1 H), 4.08–4.16 (m, 1 H), 4.00–4.09 (m, 2 H), 3.87–3.96 (m, 1 H), 3.67–3.74 (m, 1 H), 3.62–3.66 (m, 1 H), 3.56–3.61 (m, 1 H), 3.20 (s, 3 H), 2.13–2.31 (m, 2 H), 1.91–2.04 (m, 1 H), 1.69–1.87 (m, 2 H), 1.60–1.68 (m, 4 H), 1.30 (s, 6 H), 0.98 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 135.6, 134.8, 133.9, 133.1, 131.2, 129.6, 128.9, 127.7, 127.0, 119.9, 108.6, 93.5, 81.1, 80.1, 73.4, 72.7, 65.6, 60.4, 55.3, 38.7, 35.8, 34.3, 27.3, 27.0, 23.1, 19.3. IR (neat): 2930, 2858, 1155, 1106, 1033, 704 cm^–1. MS (ESI): m/z = 643 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₇H₅₂SiO₆Na: 643.3430; found: 643.3444.