Relay‐Heck Cross‐Coupling Between Alkenyl Halides and Unsaturated Alcohols in the Synthesis of Open‐Chain Analogues of Musk Odorant Vulcanolide

Abstract

Unactivated alkenyl iodides and bromides underwent an unprecedented palladium-catalyzed relay-Heck cross-coupling with a whole range of alkenols of different chain lengths linking the alkene and the alcohol, affording unsaturated aldehydes and ketones in moderate to good yields. In contrast, alkenyl triflates were not suitable partners for this reaction. This method allowed the preparation of open-chain analogues of the musk odorant Vulcanolide, several of which retained key olfactory properties of the parent molecule.

Transition Metal‐Catalyzed Functionalization of Nonallylic Alkenyl Alcohols via Chain‐Walking Strategies

“…To date, palladium‐catalyzed chain‐walking reactions of alkenyl alcohols with aryl halides have been well‐established. Furthermore, cyclic alkenyl halides have also been found to be effective coupling partners, as demonstrated in the Lenormand group (Scheme 1) [26]. In this reaction, various kinds of aldehydes 3 (Scheme 1a) and ketones 5 (Scheme 2a) were isolated in moderate to good yields in the presence of phosphine ligand L1 .…”

Transition Metal‐Catalyzed Functionalization of Nonallylic Alkenyl Alcohols via Chain‐Walking Strategies

“…To date, palladium‐catalyzed chain‐walking reactions of alkenyl alcohols with aryl halides have been well‐established. Furthermore, cyclic alkenyl halides have also been found to be effective coupling partners, as demonstrated in the Lenormand group (Scheme 1) [26]. In this reaction, various kinds of aldehydes 3 (Scheme 1a) and ketones 5 (Scheme 2a) were isolated in moderate to good yields in the presence of phosphine ligand L1 .…”

AlCl3‐Promoted Conia‐Ene‐Related Cyclization of α,ω‐Diethylenic Ketones and 1,2‐ or 1,3‐Hydroalkenylation of Unactivated Cyclopropanes

“…As part of our program devoted to the discovery of novel odorant molecules, [10] our attention was drawn to bicyclic ketone 1 (Figure 1). [11] It is a musky compound whose olfactory character, strength and tenacity are considered much superior to that of Cashmeran (2) (International Flavors and Fragrances Inc.), a commer-Scheme 1.…”

Transition Metal‐Catalyzed Functionalization of Nonallylic Alkenyl Alcohols via Chain‐Walking Strategies

“…To date, palladium‐catalyzed chain‐walking reactions of alkenyl alcohols with aryl halides have been well‐established. Furthermore, cyclic alkenyl halides have also been found to be effective coupling partners, as demonstrated in the Lenormand group (Scheme 1) [26]. In this reaction, various kinds of aldehydes 3 (Scheme 1a) and ketones 5 (Scheme 2a) were isolated in moderate to good yields in the presence of phosphine ligand L1 .…”

AlCl3‐Promoted Conia‐Ene‐Related Cyclization of α,ω‐Diethylenic Ketones and 1,2‐ or 1,3‐Hydroalkenylation of Unactivated Cyclopropanes

“…As part of our program devoted to the discovery of novel odorant molecules, [10] our attention was drawn to bicyclic ketone 1 (Figure 1). [11] It is a musky compound whose olfactory character, strength and tenacity are considered much superior to that of Cashmeran (2) (International Flavors and Fragrances Inc.), a commer-Scheme 1.…”

Transition Metal‐Catalyzed Functionalization of Nonallylic Alkenyl Alcohols via Chain‐Walking Strategies

“…To date, palladium‐catalyzed chain‐walking reactions of alkenyl alcohols with aryl halides have been well‐established. Furthermore, cyclic alkenyl halides have also been found to be effective coupling partners, as demonstrated in the Lenormand group (Scheme 1) [26]. In this reaction, various kinds of aldehydes 3 (Scheme 1a) and ketones 5 (Scheme 2a) were isolated in moderate to good yields in the presence of phosphine ligand L1 .…”

AlCl3‐Promoted Conia‐Ene‐Related Cyclization of α,ω‐Diethylenic Ketones and 1,2‐ or 1,3‐Hydroalkenylation of Unactivated Cyclopropanes

“…As part of our program devoted to the discovery of novel odorant molecules, [10] our attention was drawn to bicyclic ketone 1 (Figure 1). [11] It is a musky compound whose olfactory character, strength and tenacity are considered much superior to that of Cashmeran (2) (International Flavors and Fragrances Inc.), a commer-Scheme 1.…”