A Stereoselective Synthesis of the C20-C32 Fragment of the Phorboxazoles

J. S. Yadav; M. Satyanarayana; G. Srinivasulu; A. C. Kunwar

doi:10.1055/s-2007-982556

LETTER

A Stereoselective Synthesis of the C20-C32 Fragment of the Phorboxazoles

J. S. Yadav*^a, M. Satyanarayana^a, G. Srinivasulu^b, A. C. Kunwar^b
^a Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
^b Centre for Nuclear Magnetic Resonance, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40)7160387; e-Mail: yadavpub@iict.res.in;

Abstract

All articles of this category

Abstract

The C20-C32 fragment of the phorboxazoles was realized in a stereoconvergent manner utilizing a desymmetrization approach. This successful strategy involves epimerization and modified Julia olefination as key steps.

Keywords

phorboxazole - desymmetrization - epimerization - Julia olefination

Full Text

References

References and Notes

<A NAME="RD29306ST-1A">1a</A> Searle PA. Molinski TF. J. Am. Chem. Soc. 1995, 117: 8126

<A NAME="RD29306ST-1B">1b</A> Searle PA. Molinski TF. Brzezinski LJ. Leahy JW. J. Am. Chem. Soc. 1996, 118: 9422

<A NAME="RD29306ST-1C">1c</A> Molinski TF. Tetrahedron Lett. 1996, 37: 7879

<A NAME="RD29306ST-2A">2a</A> Ye T. Pattenden G. Tetrahedron Lett. 1998, 39: 319

<A NAME="RD29306ST-2B">2b</A> Pattenden G. Plowright AT. Tornos JA. Ye T. Tetrahedron Lett. 1998, 39: 6099

<A NAME="RD29306ST-2C">2c</A> Paterson I. Arnott EA. Tetrahedron Lett. 1998, 39: 7185

<A NAME="RD29306ST-2D">2d</A> Williams DR. Clark MP. Berliner MA. Tetrahedron Lett. 1999, 40: 2287

<A NAME="RD29306ST-2E">2e</A> Williams DR. Clark MP. Tetrahedron Lett. 1999, 40: 2291

<A NAME="RD29306ST-2F">2f</A> Wolbers P. Misske AM. Hoffmann HMR. Tetrahedron Lett. 1999, 40: 4527

<A NAME="RD29306ST-2G">2g</A> Wolbers P. Hoffmann HMR. Synthesis 1999, 797

<A NAME="RD29306ST-2H">2h</A> Wolbers P. Hoffmann HMR. Tetrahedron 1999, 55: 1905

<A NAME="RD29306ST-2I">2i</A> Misske AM. Hoffmann HMR. Tetrahedron 1999, 55: 4315

<A NAME="RD29306ST-2J">2j</A> Rychnovsky SD. Thomas CR. Org. Lett. 2000, 2: 1217

<A NAME="RD29306ST-2K">2k</A> Donaldson WA. Greer PB. Tetrahedron Lett. 2000, 41: 3801

<A NAME="RD29306ST-2L">2l</A> Huang H. Panek JS. Org. Lett. 2001, 3: 1693

<A NAME="RD29306ST-2M">2m</A> González MA. Pattenden G. Angew. Chem. Int. Ed. 2003, 42: 1255

<A NAME="RD29306ST-2N">2n</A> Paterson I. Luckhurst CA. Tetrahedron Lett. 2003, 44: 3749

<A NAME="RD29306ST-2O">2o</A> Chakraborty TK. Reddy VR. Reddy TJ. Tetrahedron 2003, 59: 8613

<A NAME="RD29306ST-3A">3a</A> Forsyth CJ. Ahmed F. Cink RD. Lee CS. J. Am. Chem. Soc. 1998, 120: 5597

<A NAME="RD29306ST-3B">3b</A> Evans DA. Fitch DM. Smith TE. Cee VJ. J. Am. Chem. Soc. 2000, 122: 10033

<A NAME="RD29306ST-3C">3c</A> Smith AB. Minbiole KP. Verhoest PR. Schelhaas M. J. Am. Chem. Soc. 2001, 123: 10942

<A NAME="RD29306ST-3D">3d</A> González MA. Pattenden G. Angew. Chem. Int. Ed. 2003, 42: 1255

<A NAME="RD29306ST-3E">3e</A> Williams DR. Kiryanov AA. Emde U. Clark MP. Berliner MA. Reeves JT. Angew Chem. Int. Ed. 2003, 42: 1258

<A NAME="RD29306ST-3F">3f</A> Smith AB. Razler TM. Ciavarri JP. Hirose T. Ishikawa T. Org. Lett. 2005, 7: 4399

<A NAME="RD29306ST-3G">3g</A> Li DR. Zhang DH. Sun CY. Zhang JW. Yang L. Chen J. Liu B. Su C. Zhou WS. Lin GQ. Chemistry 2006, 12: 1185

<A NAME="RD29306ST-4A">4a</A> Forsyth CJ. Ying L. Chen J. La Clair JJ. J. Am. Chem. Soc. 2006, 128: 3858

<A NAME="RD29306ST-4B">4b</A> Uckun FM. Forsyth CJ. Bioorg. Med. Chem. Lett. 2001, 11: 1181

<A NAME="RD29306ST-4C">4c</A> Chen J. Ying L. Hansen TM. Engler MM. Lee CS. La Clain JJ. Forsyth CJ. Bioorg. Med. Chem. Lett. 2006, 16: 901

<A NAME="RD29306ST-4D">4d</A> Smith AB. Razler TM. Pettit GR. Chapuis J.-C. Org. Lett. 2005, 7: 4403

<A NAME="RD29306ST-5A">5a</A> Yadav JS. Rao CS. Chandrasekhar S. Ramarao AV. Tetrahedron Lett. 1995, 36: 7717

<A NAME="RD29306ST-5B">5b</A> Yadav JS. Abraham S. Reddy MM. Sabitha G. Sankar AR. Kunwar AC. Tetrahedron Lett. 2001, 42: 4713

<A NAME="RD29306ST-5C">5c</A> Yadav JS. Abraham S. Reddy MM. Sabitha G. Sankar AR. Kunwar AC. Tetrahedron Lett. 2002, 43: 3453

<A NAME="RD29306ST-5D">5d</A> Yadav JS. Md. Ahmed M. Tetrahedron Lett. 2002, 43: 7147

<A NAME="RD29306ST-5E">5e</A> Yadav JS. Reddy KB. Sabitha G. Tetrahedron Lett. 2004, 45: 6475

<A NAME="RD29306ST-5F">5f</A> Yadav JS. Srinivas R. Sathaiah K. Tetrahedron Lett. 2006, 47: 1603

<A NAME="RD29306ST-6">6</A> Snider BB. Song F. Org. Lett. 2001, 3: 1817

<A NAME="RD29306ST-7A">7a</A> Bernsmann H. Gruner M. Fröhlich R. Metz P. Tetrahedron Lett. 2001, 42: 5377

<A NAME="RD29306ST-7B">7b</A> Klotz P. Mann A. Tetrahedron Lett. 2003, 44: 1927

<A NAME="RD29306ST-8">8</A> Bolitt V. Mioskowski C. Kollah RO. Manna S. Rajapaksa D. Falck JR. J. Am. Chem. Soc. 1991, 113: 6320

The six-membered ring is in the chair form ⁵C₂ conformation. C1-H, C3-H and C5-H have axial orientations confirmed by NOE enhancement between C1-H/C5-H, C1-H/C3-H and C3-H/C5-H and also between C4-Me/C2-H (Figure [1] ). This arrangement is also strongly supported by the coupling constants J _C1-H-C2-H = 10.57 Hz, J _C3-H-C2-H = 10.57 Hz and J _C3-H-C4-H = 4.53 Hz.

Figure 1

<A NAME="RD29306ST-10">10</A> Potman RP. Janssen NJML. Scheeren JW. Nivard RJF. J. Org. Chem. 1984, 49: 3628

<A NAME="RD29306ST-11">11</A> Lafontaine JA. Provencal DP. Gardelli C. Leahy JW. J. Org. Chem. 2003, 68: 4215

<A NAME="RD29306ST-12">12</A> Entwistle DA. Jordon SI. Montgomery J. Pattenden G. Synthesis 1998, 603

<A NAME="RD29306ST-13">13</A> Mitsunobu O. Synthesis 1981, 1

<A NAME="RD29306ST-14A">14a</A> Baudin JB. Hareau G. Julia SA. Ruel O. Bull. Soc. Chim. Fr. 1993, 130: 336

<A NAME="RD29306ST-14B">14b</A> Baudin JB. Hareau G. Julia SA. Lorne R. Ruel O. Bull. Soc. Chim. Fr. 1993, 130: 856

Review on modified Julia olefination:

<A NAME="RD29306ST-14C">14c</A> Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002, 2563

Spectral Data: Compound 1 [α]_D+28.26 (c 0.01, CHCl₃); ¹H NMR (200 MHz, CDCl₃): δ = 0.82 (d, J = 6.07 Hz, 3 H), 0.96 (d, J = 6.96 Hz, 3 H), 1.60-2.16 (m, 4 H) 1.87 (s, 3 H), 2.42 (s, 3 H), 3.24 (dd, J = 5.20, 10.41 Hz, 1 H), 3.44-3.76 (m, 3 H), 4.30-4.68 (m, 5 H), 6.10 (s, 1 H), 7.20-7.34 (m, 10 H), 7.38 (s, 1 H); ¹³C NMR (50 MHz, CDCl₃): δ = 5.80, 13.23, 13.69, 18.72, 33.02, 33,38, 34.44, 67.03, 69.97, 72.95, 74.46, 76.28, 76.92, 77.56, 79.77, 83.99, 119.46, 127.44, 127.62, 128.26, 135.18, 137.24, 138.49, 138.67; LC-MS: m/z = 476 [M + H⁺].
Compound 10: [α]_D+57.29 (c 1.85, CHCl₃); ¹H NMR (200 MHz, CDCl₃): δ = 0.98 (d, J = 7.18 Hz, 3 H), 1.05 (d, J = 7.81 Hz, 3 H), 2.0-2.20 (m, 2 H), 2.25-2.36 (dd, J = 3.9, 15.6 Hz, 1 H), 2.57-2.70 (m, 1 H), 3.30 (s, 3 H), 3.68 (s, 3 H), 3.84 (m, 1 H), 4.25-4.34 (m, 1 H), 4.47-4.50 (m, 3 H), 7.22-7.30 (m, 5 H); ¹³C NMR (50 MHz, CDCl₃): δ = 8.91, 12.89, 35.45, 36.60, 37.31, 51.53, 54.74, 67.34, 69.99, 75.36, 103.42, 127.03, 127.20, 128.14, 172.00; MS (FAB): m/z = 291 [M⁺- OMe].
Compound 13: colorless oil; [α]_D+50.5 (c 1.00, CHCl₃); IR (KBr): 3029, 2871, 1743 cm^-1;¹H NMR (200 MHz, CDCl₃): δ = 1.00 (d, J = 7.23 Hz, 3 H), 1.32 (d, J = 7.23 Hz, 3 H), 1.72-2.12 (m, 2 H), 2.24-2.40 (m, 1 H), 2.72-2.88 (m, 1 H), 3.52-3.72 (m, 2 H), 3.88 (t, J = 5.78 Hz, 1 H), 4.44-4.56 (m, 5 H), 7.24-7.36 (m, 10 H); ¹³C NMR (50 MHz, CDCl₃): δ = 8.64, 12.57, 32.41, 35.56, 39.46, 66.24, 73.19, 73.56, 76.26, 127.44, 127.73, 128.40, 137.78, 138.15, 174.34; MS (FAB): m/z = 369 [M + H⁺].
Compound 14: colorless oil; [α]_D +76.5 (c 1.00, CHCl₃); ¹H NMR (200 MHz, CDCl₃): δ = 0.96 (d, J = 7.55, 3 H), 1.36 (d, J = 6.79 Hz, 3 H), 1.72-1.84 (m, 1 H), 1.96-2.08 (m 1 H), 2.24-2.32 (m, 1 H), 2.44-2.56 (m, 1 H), 3.48 (dd, J = 3.77, 9.82 Hz, 1 H), 3.54-3.60 (m, 2 H), 4.32-4.64 (m, 5 H), 7.24-7.32 (m, 10 H); ¹³C NMR (75 MHz, CDCl₃): δ = 4.72, 14.61, 33.03, 38.31, 65.92, 70.56, 73.17, 76.15, 80.39, 127.61, 128.43, 137.59, 173.54; MS (FAB): m/z = 369 [M + H⁺].
Compound 16: colorless oil; [α]_D +54.54 (c 0.01, CHCl₃); IR (KBr): 2961, 2926, 2179 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 0.17 (s, 9 H), 0.96 (d, J = 6.79 Hz, 3 H), 1.04 (d, J = 6.79 Hz, 3 H), 1.56-1.68 (m, 1 H), 1.76-2.04 (m, 3 H), 3.09 (dd, J = 4.53, 10.57 Hz, 1 H), 3.46-3.60 (m, 2 H), 3.60-3.64 (d, J = 10.57 Hz, 1 H), 4.10 (q, J = 7.55, 14.35 Hz, 1 H), 4.30 (d, J = 11.33 Hz, 1 H), 4.49 (s, 2 H), 4.59 (d, J = 12.06 Hz, 1 H), 7.20-7.34 (m, 10 H); ¹³C NMR (50 MHz, CDCl₃): δ = 5.99, 14.19, 33.33, 34.47, 37.23, 67.02, 69.96, 73.71, 75.98, 83.05, 103.65, 127.74, 128.44, 138.59; LC-MS: m/z = 450 [M + H⁺].
Compound 4: colorless oil; [α]_D +90.0 (c 0.01, CHCl₃); IR (KBr): 2969, 2926, 2858, 1718 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 0.84-0.98 (m, 6 H), 1.60-2.20 (m, 4 H), 2.11 (s, 3 H) 3.18 (dd, J = 4.68, 10.93 Hz, 1 H), 3.32 (d, J = 10.93 Hz, 1 H), 3.44-3.64 (m, 3 H), 4.32-4.70 (m, 4 H), 7.28 (m, 10 H);¹³C NMR (75 MHz, CDCl₃): δ = 6.98, 19.44, 26.51, 27.39, 28.40, 60.78, 64.133, 67.09, 69.16, 70.69, 71.11, 71.53, 77.26, 81.76, 121.69, 121.77, 122.44, 122.45, 132.39, 132.49, 201.15; LC-MS: m/z = 397 [M + H⁺].
Compound 5:IR (KBr): 3029, 2871, 1743 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 2.28 (s, 3 H), 4.71 (s, 2 H), 7.54-7.69 (m, 3 H), 7.99 (m, 1 H), 8.24 (m, 1 H); ESI-MS: m/z 295 [M + H⁺].