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Synlett 2007(13): 2049-2052  
DOI: 10.1055/s-2007-984896
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Formal Synthesis of Crocacin C via Prins Cyclization

J. S. Yadav*, M. Sridhar Reddy, P. Purushothama Rao, A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40)27160512; e-Mail: yadavpub@iict.res.in;
Further Information

Publication History

Received 6 October 2006
Publication Date:
12 July 2007 (online)

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Abstract

A formal synthesis of crocacin C is described proving the versatility of Prins cyclization in natural product synthesis. The ­approach is convergent and highly stereoselective. Cross-metathesis and Heck reactions were utilized for the insertion of an aromatic group in a stereocontrolled manner.

Key words

crocacins - Prins cyclization - olefin rearrangement - cross-metathesis

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Selected Physical Data. Compound 9: clear oil; R f = 0.5 (EtOAc-hexane, 1:9). IR (KBr): νmax = 2828, 2856, 1643, 1458, 1092, 838, 697 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.37-7.17 (m, 5 H), 4.47 (d, 1 H, J = 12.0 Hz), 4.42 (d, 1 H, J = 12.0 Hz), 3.57 (dd, 1 H, J = 10.5, 5.2 Hz), 3.50-3.42 (m, 2 H), 3.33-3.23 (m, 5 H), 3.16 (dd, 1 H, J = 9.8, 1.5 Hz), 2.87 (dt, 1 H, J = 10.5, 4.5 Hz), 2.14-1.98 (m, 2 H), 1.50-1.38 (m, 1 H), 1.10-1.02 (m, 1 H), 0.88 (d, 3 H, J = 6.4 Hz), 0.84 (s, 9 H), 0.81 (d, 3 H, J = 6.7 Hz), 0.03 (s, 6 H). 13C NMR (75 MHz, CDCl3): δ = 138.8, 128.2, 127.4, 127.3, 82.5, 79.9, 75.9, 73.5, 72.9, 66.4, 56.0, 38.4, 34.2, 33.0, 25.8, 18.2, 12.1, 9.6, -5.2, -5.3. LSI-MS: m/z = 445 [M+ + Na], 423 [M+ + H].
Compound 13: white solid; mp 158-160 °C; R f = 0.6 (EtOAc-hexane, 1:9). IR (KBr): νmax = 2969, 2928, 2880, 1678, 1433, 1099, 712 cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.60-4.54 (m, 3 H), 3.72 (dd, 1 H, J = 10.1, 3.1 Hz), 3.57 (t, 1 H, J = 8.5 Hz), 3.44 (dt, 1 H, J = 8.5, 2.3 Hz), 3.40-3.29 (m, 4 H), 3.28 (s, 3 H), 2.12-2.02 (m, 1 H), 1.80-1.68 (m, 1 H), 1.72 (s, 3 H), 0.94 (d, 3 H, J = 7.0 Hz), 0.90 (d, 3 H, J = 7.0 Hz). 13C NMR (75 MHz, CDCl3): δ = 153.2, 96.4, 95.9, 78.9, 78.3, 70.0, 55.1, 54.9, 33.8, 33.7, 19.6, 13.7, 9.5. LSI-MS: m/z = 267 [M+ + Na].
Compound 5: clear oil; R f = 0.3 (EtOAc-hexane, 1:3); [α]D 20 -3.8 (c 1.80, CH2Cl2); IR (film): ν max = 3453, 2970, 2931, 2827, 1599, 1454, 1374, 1191, 1090, 971 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.40 (d, 2 H, J = 7.6 Hz), 7.32 (t, 2 H, J = 6.8 Hz), 7.24 (tt, 1 H, J = 1.5, 7.6 Hz), 6.59 (d, 1 H, J = 16.0 Hz), 6.21 (dd, 1 H, J = 7.6, 16.0 Hz), 4.07 (dd, 1 H, J = 1.5, 7.6 Hz), 3.82 (dd, 1 H, J = 3.8, 11.4 Hz), 3.56 (dd, 1 H, J = 11.4, 4.5 Hz), 3.52 (s, 3 H), 3.31 (s, 3 H), 3.29 (dd, 1 H, J = 3.0, 9.9 Hz), 3.01 (br s, 1 H), 1.90-1.85 (m, 2 H), 1.20 (d, 3 H, J = 6.8 Hz), 0.91 (d, 3 H, J = 6.8 Hz). 13C NMR (75 MHz, CDCl3): δ = 136.7, 132.1, 129.2, 128.6, 127.6, 126.4, 88.2, 81.1, 64.3, 61.5, 56.3, 42.2, 35.8, 16.1, 10.3. ESI-HRMS: m/z calcd for C17H26O3Na [M + Na+]: 301.1779; found: 301.1791.
Compound 18: light yellowish oil; R f = 0.5 (EtOAc-hexane, 1:9); [α]D 20 -6.7 (c 0.2 CHCl3) {Lit. [3d] [α]D 20 -7.91 (c 0.2 CHCl3)}. IR (film): νmax = 2974, 2929, 1710, 1609, 1450, 1367, 1238, 1154, 1092, 1042, 972 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.33 (d, 2 H, J = 7.5 Hz) 7.25 (t, 2 H, J = 7.5 Hz), 7.20 (tt, 1 H, J = 8.3, 1.5 Hz), 6.55 (d, 1 H, J = 15.8), 6.10 (m, 2 H), 6.05 (d, 1 H, J = 15.8 Hz), 5.63 (s, 1 H), 4.09 (q, 2 H, J = 6.7 Hz), 4.03 (m, 1 H), 3.51 (s, 3 H), 3.29 (s, 3 H), 3.13 (dd, 1 H, J = 9.8, 2.2 Hz), 2.50 (m, 2 H), 2.26 (d, 3 H, J = 1.5 Hz), 1.50 (m, 1 H) 1.26 (t, 2 H, J = 7.5 Hz), 1.19 (d, 3 H, J = 6.7 Hz), 0.82 (d, 3 H, J = 6.7 Hz). 13C NMR (50 MHz, CDCl3): δ = 167.2, 152.5, 140.0, 136.7, 133.9, 132.0, 129.1, 128.5, 127.5, 126.3, 118.0, 86.3, 81.0, 61.4, 59.5, 56.4, 42.6, 40.0, 18.7, 14.3, 13.9, 9.6. ESI-HRMS: m/z calcd for C24H34O4Na [M + Na+]: 409.2354; found: 409.2356.

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Sulfone 17 was prepared from mercaptobenzothiazole in three steps in 62% overall yield as shown in Scheme 3.