Stereoselective Synthesis of the C15-C24 Fragment of Discodermolide by Desymmetrization of a meso Dialdehyde

Abstract

The five stereogenic centers in C15-C24 fragment of discodermolide was directly controlled by desymmetrization of a meso dialdehyde by using an optically active crotyltitanium complex.

Key words

desymmetrization - meso dialdehyde - crotyltitanation - discodermolide

References

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• Total synthesis:
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12

Spectroscopic data for compound 6: [α]_D ²⁰ +15.5 (c 0.45, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 6.64 (dd, J = 2.2 Hz and 9.9 Hz, 1 H), 5.90 (dd, J = 2.2 Hz and 9.9 Hz, 1 H), 4.67 (d, J = 6.6 Hz, 1 H), 4.63 (d, J = 6.6 Hz, 1 H), 4.13 (dd, J = 2.9 Hz and 9.9 Hz, 1 H), 3.69 (dd, J = 2.9 Hz and 7.3 Hz, 1 H), 3.50 (m, 2 H), 3.35 (s, 3 H), 2.66 (m, 1 H), 2.00 (m, 1 H), 1.90 (m, 1 H), 1.10 (d, J = 7.3 Hz, 3 H), 1.05 (d, J = 7.0 Hz, 3 H), 0.88 (s, 9 H), 0.86 (d, J = 7.0 Hz, 3 H), 0.01 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.6 (s), 151.5 (d), 119.9 (d), 98.5 (t), 83.4 (d), 80.2 (d), 65.7 (t), 55.9 (q), 37.6 (d), 36.8 (d), 30.8 (d), 25.7 (3q), 18.0 (s), 15.9 (q), 10.6 (q), 10.0 (q), -5.5 (q), -5.6 (q). IR (neat): 2960, 1730, 1460, 1380, 1240 cm^-1. MS (EI, 70 eV): m/z (%) = 386 [M, absent], 329 (19) [M - t-Bu], 283 (11), 267 (100), 249 (37), 213 (27), 183 (38), 145 (72), 122 (71), 89 (55), 75 (48).

13

Spectroscopic data for compound 8: [α]_D ²⁰ +61.0 (c 5.3, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 6.50 (dt apparent, J = 10.7 Hz and 16.9 Hz, 1 H ), 6.00 (t apparent, J = 10.7 Hz, 1 H), 5.45 (t apparent, J = 9.9 Hz, 1 H), 5.15 (dd, J = 16.9 Hz and 1.84, 1 H), 5.10 (dd, J = 9.9 Hz and 1.84, 1 H), 4.64 (d, J = 6.6 Hz, 1 H), 4.60 (d, J = 6.6 Hz, 1 H), 3.60-3.45 (m, 4 H), 3.30 (s, 3 H), 2.95-2.70 (m, 1 H + OH), 2.00-1.8 (m, 2 H), 1.00 (d, J = 7.0 Hz, 3 H), 0.95 (d, J = 7.0 Hz, 3 H), 0.90 (s, 9 H), 0.80 (d, J = 7.0 Hz, 3 H), 0.09 (s, 3 H), 0.06 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 135.2 (d), 132.1 (d), 129.1 (d), 117.3 (t), 98.7 (t), 80.8 (d), 75.9 (d), 65.0 (t), 55.8 (q), 39.2 (d), 37.3 (d), 37.2 (d), 26.0 (3q), 18.4 (q), 18.3 (s), 11.0 (q), 10.2 (q), -3.6 (q), -3.7 (q). IR (neat): 3450, 2960, 1460, 1380, 1260, 1150, 1030 cm^-1.