Enantiocontrolled Synthesis of a Chiral Building Block via Diastereoselective Ring-Closing Metathesis

Yuri Murakami; Mitsuru Shindo; Kozo Shishido

doi:10.1055/s-2005-862388

LETTER

Enantiocontrolled Synthesis of a Chiral Building Block via Diastereoselective Ring-Closing Metathesis

Yuri Murakami, Mitsuru Shindo, Kozo Shishido*
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6339575; e-Mail: shishido@ph.tokushima-u.ac.jp;

Abstract

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Abstract

An enantiocontrolled construction of a chiral building block, which had been converted into an indole alkaloid (-)-eburnamonine, has been accomplished using a diastereoselective ring-closing metathesis for the construction of the quaternary stereogenic center.

Key words

ring-closing metathesis - indole alkaloid - diastereoselective synthesis - asymmetric induction - fragmentation reaction

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References

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The trienes 3a,e,f were prepared from 3 (R¹ = H, R² = TBDPS) by conventional silylation, benzylation and MOM ether formation, respectively. The trienes 3b-d were synthesized from the diol 3 (R¹ = R² = H), which was derived from 3 (R¹ = H, R² = TBDPS) by desilylation with TBAF, by sequential acylation and TMS ether formation.

10

The major diastereomer of compound 4a: colorless oil; [α]_D ²⁶ -27.7 (c 1.12, CHCl₃). IR (neat): 3348, 3071, 1194, 915 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.04 (s, 9 H), 1.43 (m, 2 H), 1.56-1.79 (m, 5 H), 3.65-3.77 (m, 2 H), 4.06 (d, J = 3.6 Hz, 1 H), 4.82 (dd, J = 17.6, 1.2 Hz, 1 H), 4.95 (dd, J = 10.4, 1.2 Hz, 1 H), 5.59 (dd, J = 17.6, 10.4 Hz, 1 H), 5.61 (d, J = 10.4 Hz, 1 H), 5.78 (dd, J = 10.4, 3.6 Hz, 1 H), 7.35-7.66 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.16, 26.88, 27.94, 28.91, 41.10, 43.18, 60.55, 64.46, 113.32, 127.54, 128.87, 129.49, 133.77, 135.49, 135.85, 143.70. HRMS (FAB): m/z calcd for C₂₆H₃₂O₂Si: 427.2069 [M + Na]⁺; found: 427.2030 [M + Na]⁺.

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