The Synthesis of (Z)‐Trisubstituted Allylic Alcohols by the Selective 1,4‐Hydrogenation of Dienol Esters: Improved Synthesis of (−)‐β‐Santalol

Abstract

(E)-Trisubstituted allylic alcohols are commonly prepared from the corresponding (E)-enals, themselves readily accessible by a simple aldol condensation reaction. We demonstrate that these very same (E)-enals can be converted into (Z)-trisubstituted allylic acetates (and thus alcohols) by a ruthenium-catalyzed 1,4-hydrogenation of the corresponding dienol acetates. This simple solution to a long-lasting problem was applied to an industrially feasible synthesis of (-)-β-santalol.

On the Functional Group Tolerance of Ester Hydrogenation and Polyester Depolymerisation Catalysed by Ruthenium Complexes of Tridentate Aminophosphine Ligands

“…The reduction of the conjugated dienoate ethyl sorbate could be part of a very direct route to the fragrance molecule leaf alcohol involving a stereospecific 1,4‐ cis ‐hydrogenation of sorbic alcohol using [(Cp*)Ru(cod)][BF 4 ]‐type complexes (Cp*=1,2,3,4,5‐pentamethylcyclopentadienyl; cod=1,5‐cyclooctadiene) to produce the monounsaturated alcohol with high selectivity 9a. c However, the chemoselective ester hydrogenation of sorbate esters to unsaturated alcohols, to our knowledge, has never been achieved, and conjugated esters remain a challenge even for the most chemoselective catalysts 9a. 10…”

Copper‐Catalyzed Cyclization–Fragmentations of Enynols

“…[7] Herein, we describe the copper(I)-catalyzed cycloisomerization of several 5-en-1-yn-3-ols and an exploratory extension to 6-en-1-yn-4-ols, which has led to the discovery of an unprecedented metathesis fragmentation pathway and has highlighted the complementary reactivity of the copper and gold catalysts.…”

“…Synthesis of (À)-b-santalol ((À)-5) by cyclization-fragmentation of 3. [7] sulted that diastereomers 6 and 7 exhibit different selectivities and reactivities ( Table 1, entries 1 and 2 vs. entries 3 and 4). The ease of fragmentation depends on the ability of the C À C bond to break and to adopt a perpendicular arrangement with respect to the plane defined by the tertiary carbenium-ion system (i.e., parallel to the empty p orbital; see intermediate H in Table 1; not possible in the example of Scheme 1) and the amount of accompanying strain release.…”

“…[5b] Recently, we reported a new enantioselective, direct synthesis of the highly prized natural sandalwood odorant (À)-b-santalol (À)-5, which is based on a copper-catalyzed cyclization-fragmentation reaction (Scheme 3). [7] Herein, we describe the copper(I)-catalyzed cycloisomerization of several 5-en-1-yn-3-ols and an exploratory extension to 6-en-1-yn-4-ols, which has led to the discovery of an unprecedented metathesis fragmentation pathway and has highlighted the complementary reactivity of the copper and gold catalysts.…”

Natural sesquiterpenoids

“…113 A rapid and efficient method for determining the fumagillin residues in honey by HPLC-MS has been described. 113 A rapid and efficient method for determining the fumagillin residues in honey by HPLC-MS has been described.…”