TMSI-Mediated Prins Cyclization: Diastereoselective Synthesis of 4-Iodo-2,6-Disubstituted Tetrahydropyrans and Synthesis of (±)-Centrolobine

Gowravaram Sabitha; K. Bhaskar Reddy; G. S. Kiran Kumar Reddy; Narjis Fatima; J. S. Yadav

doi:10.1055/s-2005-872668

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Synlett 2005(15): 2347-2351
DOI: 10.1055/s-2005-872668

LETTER

TMSI-Mediated Prins Cyclization: Diastereoselective Synthesis of 4-Iodo-2,6-Disubstituted Tetrahydropyrans and Synthesis of (±)-Centrolobine [1]

Gowravaram Sabitha*, K. Bhaskar Reddy, G. S. Kiran Kumar Reddy, Narjis Fatima, J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: +91(40)27160512; e-Mail: sabitha@iictnet.org;

Further Information

Publication History

Received 26 May 2005
Publication Date:
07 September 2005 (online)

Abstract
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Abstract

The reaction of aldehydes with homoallyl alcohols in the presence of TMSI generated in situ from TMSCl and NaI produced 4-iodo-tetrahydropyrans in good yields as a mixture of diastereoisomers, which are separated and characterized. These iodo pyrans are reported for the first time. This methodology was extended to the synthesis of (±)-centrolobine.

Key words

Prins reaction - iodotetrahydropyrans - homoallyl alcohols - TMSI - (±)-centrolobine

1

IICT communication number: 050506.

References

For reviews, see:
2a Arundale E. Mikeska LA. Chem. Rev. 1952, 51: 505

Article in Thieme Connect Google Scholar
2b Adams DR. Bhatnagar SP. Synthesis 1977, 661

Article in Thieme Connect Google Scholar
3 Nicolaou KC. Sorensen EJ. Classics in Total Synthesis VCH; Weinheim: 1996.

Google Scholar
4a Wei ZY. Li JS. Wang D. Chan T.-H. Tetrahedron Lett. 1987, 28: 3441

Crossref Google Scholar
4b Wei ZY. Wang D. Li JS. Chan TH. J. Org. Chem. 1989, 54: 5768

Crossref Google Scholar
5 Coppi L. Ricci A. Taddei M. J. Org. Chem. 1988, 53: 911

Crossref Google Scholar
6a Yang J. Li C.-J. Synlett 1999, 717

Crossref Google Scholar
6b Yang J. Viswanathan GS. Li C.-J. Tetrahedron Lett. 1999, 40: 1627

Crossref Google Scholar
7 Zhang W.-C. Viswanathan G. Li CJ. Chem. Commun. 1999, 291

Crossref Google Scholar
8 Yadav JS. Reddy BVS. Kumar GM. Murthy CVSR. Tetrahedron Lett. 2001, 42: 89

Crossref Google Scholar
9 Yadav JS. Reddy BVS. Sekhar CK. Gunasekhar D. Synthesis 2001, 885

Article in Thieme Connect Google Scholar
10a Sabitha G. Reddy GSKK. Srinivas Reddy C. Yadav JS. Synlett 2003, 858

Crossref Google Scholar
10b Sabitha G. Reddy GSKK. Srinivas Reddy C. Yadav JS. Tetrahedron Lett. 2003, 44: 4129

Crossref Google Scholar
10c Sabitha G. Yadav JS. Synth. Commun. 1998, 28: 3065

Crossref Google Scholar
10d Sabitha G. Abraham S. Reddy BVS. Yadav JS. Tetrahedron Lett. 1999, 40: 1569

Crossref Google Scholar
10e Sabitha G. Reddy GSKK. Reddy KB. Yadav JS. Synthesis 2004, 263

Crossref Google Scholar
10f Sabitha G. Reddy GSKK. Rajkumar M. Yadav JS. Ramakrishna KVS. Kunwar AC. Tetrahedron Lett. 2003, 44: 7455

Crossref Google Scholar
12a Craveiro AA. Prado da Costa A. Gottlieb OR. Welerson de Albuquerque PC. Phytochemistry 1970, 9: 1869

Crossref PubMed Google Scholar
12b De Albuquerque IL. Galeffi C. Casinovi CG. Marini-Bettolo GB. Gazz. Chim. Ital. 1964, 287

Crossref PubMed Google Scholar
12c Marumoto S. Jaber JJ. Vitale JP. Rychnovsky SD. Org. Lett. 2002, 4: 3919

Crossref PubMed Google Scholar
12d Carreno MC. Mazery RD. Urbano A. Colobert F. Solladie G. J. Org. Chem. 2003, 68: 7779

Crossref PubMed Google Scholar

1

IICT communication number: 050506.

11

Experimental.
To a stirred solution of homoallyl alcohol 1c (1 g, 5.7 mmol), anisaldehyde (2c, 773 mg, 5.7 mmol), and NaI (852 mg, 5.7 mmol) in dry MeCN (10mL) was added TMSCl (0.72 mL, 5.7 mmol) dropwise at r.t. After the reaction was complete as indicated by TLC (see Table [1] ), the reaction mixture was taken up into Et₂O, washed with Na₂S₂O₃ solution, brine and dried over anhyd Na₂SO₄. Evaporation of the solvent afforded a crude product, which was further purified by column chromatography (hexane-EtOAc, 98: 2). The diastereomers 3c and 4c were obtained in 7.5:2.5 ratio, respectively, and in a total yield of 92%.
Representative Spectral Data:
Compound 3c: ¹H NMR (400 MHz, CDCl₃): δ = 7.28 (dd, J _H9-H10 = 8.6 Hz, J _H9-H9 = 2.2 Hz, 2 H, H-9), 6.89 (dd,
J _H9-H10 = 8.6 Hz, J _H9-H9 = 2.2 Hz, 2 H, H-10), 7.26-7.17 (m, 5 H, CH₂-Ph), 4.37 (tt, J _H4-H5-Pro-R = 4.2 Hz, J _H4-H3-Pro-S = 4.2 Hz, J _H4-H5-Pro-S = 12.3 Hz, J _H4-H3-Pro-R = 12.3 Hz,1 H, H-4), 4.29 (dd, J _H2-H3vPro-S = 2.1 Hz, J _H2-H3-Pro-R = 11.2 Hz, 1 H, H-2), 3.81 (s, 3 H, OMe), 3.44 (dddd, J _H6-H5-Pro-R = 2.1 Hz, J _H6-H5-Pro-S = 10.8 Hz, J _H6-H7 = 8.3 Hz, J _H6-H7 _′ = 4.2 Hz, 1 H, H-6), 2.79 (m, 1 H, H-8), 2.68 (m,1 H, H-7′), 2.54 (ddd, J _H3-Pro-S-H2 = 2.1 Hz, J _H3-Pro-S-H4 = 4.2 Hz, J _{H3-Pro-S-H3-Pro-R} = 13.1 Hz, 1 H, H₃-Pro-S), 2.37 (ddd, J _H4-H5-Pro-R = 4.2 Hz, J _H6-H5-Pro-R = 2.1 Hz, J _{H5-Pro-S-H5-Pro-R} = 12.9 Hz, J _{H3-Pro-S-H5-Pro-R} = 2.1 Hz, 1 H, H₅-Pro-R), 2.19 (ddd,
J _H3-Pro-R-H4 = 12.3 Hz, J _{H3-Pro-S-H3-Pro-R} = 13.1 Hz,
J _H2-H3-Pro-R = 11.2 Hz, 1 H, H₃-Pro-R), 2.04 (ddd, J _{H5-Pro-S-H5-Pro-R} = 12.9 Hz, J _H5-Pro-S-H4 = 12.3 Hz, J _H5-Pro-S-H6 = 10.8 Hz, 1 H, H₅-Pro-S), 1.94 (m, 1 H, H-7), 1.77 (m,1 H, H-7′). ¹³C NMR (300 MHz, CDCl₃): δ = 22.39, 31.28, 37.14, 44.89, 47.01, 55.26, 77.83, 79.99, 113.78, 125.78, 126.96, 128.31, 128.43. MS: m/z = 421 [M + H], 295 [M - I].
Compound 4c: ¹H NMR (400 MHz, CDCl₃): δ = 7.28 (dd, J _H9-H10 = 8.7 Hz, J _H9-H9 = 2.2 Hz, 2 H, H-9), 7.26-7.18 (m, 5 H, -CH₂-Ph), 6.87 (dd, J _H9-H10 = 8.7 Hz, J _H9-H9 = 2.2 Hz, 2 H, H-10), 4.93 (dddd, J _H4-H5-Pro-R = 4.6 Hz, J _H4-H5-Pro-S = 3.7 Hz, J _H4-H3-Pro-S = 4.8 Hz, J _H4-H3-Pro-R = 3.4 Hz, 1 H, H-4), 4.82 (dd, J _H2-H3-Pro-R = 10.8 Hz, J _H2-H3-Pro-S = 2.3 Hz, 1 H, H-2), 4.01 (m, 1 H, H-6), 3.80 (s, 3 H, OMe), 2.84 (m, 1 H, H-8), 2.71 (m, 1 H, H-8′), 2.21 (ddd, J _H3-Pro-S-H2 = 2.3 Hz,
J _H3-Pro-S-H4 = 4.8 Hz, J _{H3& ndash;Pro-S-H3-Pro-R} = 14.8 Hz, 1 H, H₃-Pro-S, 1 H, H₃-Pro-S), 2.05 (ddd, J _H4-H5-Pro-R = 4.6 Hz, J _H6-H5-Pro-R = 2.3 Hz, J _{H5-Pro-S-H5-Pro-R} = 14.6 Hz, 1 H, H₅-Pro-R), 1.96 (m, 1 H, H-7), 1.82 (m, 1 H, H-7′), 1.76 (ddd, J _H2-H3-Pro-R = 10.8 Hz, J _{H3-ProS-H3-Pro-R} = 14.8 Hz,
J _H4-H3-Pro-R = 3.4 Hz, 1 H, H₃-Pro-R), 1.63 (ddd,
J _{H5-Pro-R-H5-Pro-S} = 14.6 Hz, J _H4-H5-Pro-S = 3.7 Hz,
J _H6-H5-Pro-S = 10.5 Hz, 1 H, H₅-Pro-S). ¹³C NMR (300 MHz, CDCl₃): δ = 30.44, 31.87, 37.38, 40.49, 42.59, 55.25, 73.33, 75.05, 96.23, 113.82, 125.82, 127.18, 128.39, 128.47. MS: m/z = 421 [M + H], 295 [M - I].

13

(±)-Centrolobine.
White solid, mp 87-88 °C (lit. [12] 85-87 °C). ¹H NMR (300 MHz, CDCl₃): δ = 7.28 (d, J = 8.18 Hz, 2 H), 6.95 (d, J = 8.18 Hz, 2 H), 6.83 (d, J = 8.92 Hz, 2 H), 6.62 (d, J = 8.18 Hz, 2 H), 5.40 (br s, OH), 4.28 (dd, J = 2.20, 11.15 Hz, 1 H), 3.78 (s, 3 H), 3.32-3.50 (m, 1 H), 2.55-2.75 (m, 2 H), 1.55-1.95 (m, 6 H), 1.22-1.48 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.0, 153.5, 135.7, 134.2, 129.6, 126.9, 114.5, 113.4, 79.5, 77.8, 55.2, 38.4, 33.2, 31.5, 30.7, 24.8. MS: m/z = 312 [M⁺].