Enantioselective Synthesis of (−)‐β‐Santalol by a Copper‐Catalyzed Enynol Cyclization–Fragmentation Reaction

Abstract

The right cat for the desired odor: The key step in an enantioselective synthesis of the prized fragrance (−)‐β‐santalol was a highly selective copper‐catalyzed cyclization–fragmentation reaction of an enynol (see scheme). When a platinum catalyst was used for the cyclization step, the desired fragmentation did not take place; instead, a product containing a cyclopropane ring was formed with 100 % selectivity.

Gold‐ and Copper‐Catalyzed Cycloisomerizations towards the Synthesis of Thujopsanone‐Like Compounds

“…Cycloisomerization with concomitant 1,2-alkyl shift. [1] Scheme 2. Cycloisomerization with concomitant 1,2-pivalate shift.…”

“…In 2006, we reported the copper-catalyzed cycloisomerization of 5-en-1-yn-3-ols (cyclopropanation/1,2-alkyl shift; Scheme 1) [1] and related enynol esters, as exemplified by the synthesis of (À)-cubebol (Scheme 2).…”

“…Thus, 6-en-1-yn-3-ol 10 a underwent clean cyclization/ether formation to 16, in particular using Au catalysts (76-98 %) or a newly prepared Cu Itriflimidate-catalyst (94 %). The corresponding acetate 11 a underwent either the cycloisomerization with concomitant [1,2] Scheme 1. Cycloisomerization with concomitant 1,2-alkyl shift.…”

“…Cycloisomerizations of enynol esters with [1,2]-acyl shift: possible reaction pathways. cyclization (Scheme 3; A!F!G) is only operative when the cyclization is slow enough to allow the [1,2]-acyl shift to occur first. This is the case in intermolecular reactions [5b,i] and medium-sized ring closures.…”

“…[5] It has been demonstrated that esters of type 3 first undergo cyclization, then [1,2]-acyl migration, as the propargylic stereogenic center controls the stereochemical outcome of the cycloisomerization (Scheme 3; A!B!C). The alternative reaction pathway in which the [1,2]-acyl shift precedes the Abstract: In the search for a new access to thujopsanone related compounds by cycloisomerization reactions of unsaturated propargylic alcohols and acetates, we found several interesting reaction types and demonstrated the complementarity of Au, Pt, and Cu catalysts. Thus, 6-en-1-yn-3-ol 10 a underwent clean cyclization/ether formation to 16, in particular using Au catalysts (76-98 %) or a newly prepared Cu Itriflimidate-catalyst (94 %).…”