Concise Synthesis of A Steroid C/D-Ring System Using a Bicyclo[3.2.1]octane Chiral Building Block: A New Route to 25-Hydroxy-Grundmann’s Ketone

Abstract

A concise route to a steroid C/D-ring system leading to 25-hydroxy-Grundmann’s ketone has been developed along with a new chemical resolution of the chiral starting material containing a bicyclo[3.2.1]octane framework.

chiral building block - convex-face selective stereoselection - asymmetric hydrogen transfer reaction - vitamin D - steroid synthesis - Dieckmann cyclization - aldol reaction

References

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Optical purity of the product was determined by ¹H NMR measurement after transformation into the MTPA (both enantiomeric) esters of the allyl alcohol 7. ¹H NMR(300 MHz, CDCl₃) of (-)-enone 5: δ = 1.45 (qd, J = 1.1, 8.5 Hz, 1 H), 1.71 (dtd,, J = 1.1, 4.7, 8.5 Hz, 1 H), 2.02 (d, J = 1.8 Hz, 1 H), 2.47 (td, J = 8.2, 14.6 Hz, 1 H), 2.79 (t, J = 5.8 Hz, 1 H), 3.08 (q, J = 5.5 Hz, 1 H), 3.37 (s, 3 H), 4.50 (td, J = 5.2, 14.3 Hz, 1 H), 4.65 (d, J = 1.4 Hz, 1 H), 6.04 (dd, J = 1.4, 9.9 Hz, 1 H), 7.11 (ddd, J = 1.4, 6.6, 8.5 Hz, 1 H). ¹H NMR(300 MHz, CDCl₃) of (-)-allyl alcohol 7: δ = 1.64-1.71 (m, 2 H), 1.77 (d, J = 11.5 Hz, 1 H), 1.81 (dd,, J = 6.0, 14.3 Hz, 1 H), 2.02 (td, J = 9.3, 13.2 Hz, 1 H), 2.34-2.36 (m, 1 H), 2.54 (q, J = 4.9 Hz, 1 H), 3.38 (s, 3 H), 4.23 (td, J = 5.5, 11.3 Hz, 1 H), 4.60 (br.s, 1 H), 4.65 (s, 2 H), 5.53 (td, J = 2.2, 9.6 Hz, 1 H), 5.88 (td, J = 1.4, 6.3 Hz, 1 H).

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