Catalytic Enantioselective Synthesis of Adociacetylene B

Abstract

A catalytic enantioselective total synthesis of adociacetylene B (2) in five steps is reported. The efficiency of this synthesis was enabled by an asymmetric zinc alkynylation catalyzed by the proline-derived ligand (1).

Acetylides from Alkyl Propiolates as Building Blocks for C3 Homologation

“…This procedure has been effectively applied in the first catalytic and enantioselective synthesis of the adociacetylene B, a polyacetylenic biologically active natural product. [40] During the last two years, a few, significant advances in the metalation of propiolate esters using catalytic amounts of copper(I) have been reported. In a recent communication, Ma and co-workers describe the first asymmetric addition of alkyl propiolates and related conjugated terminal alkynes to 1-acylpyridinium salts catalyzed by a copper(I) complex of bis(oxazoline) 12 (Scheme 10).…”

Highly enantioselective addition of terminal alkynes to aldehydes catalyzed by a new chiral β‐sulfonamide alcohol/Ti(OiPr)4/Et2Zn/R3N catalyst system

“…46 However, that research focused solely on methyl propiolate. 3,4,32,33 Other functional alkynes such as trimethylsilylacetylene and ethynylcyclohexene are particularly desirable alkynes due to the possible use of the desilylated product for alkylation or the Sonogashira coupling [47][48][49][50][51] and the possible further tranformation of the alkene group such as epoxidation, hydroxylation, ozonolysis, and addition of carbenes, 52 respectively. However, to our knowledge, the enantioselective trimethylsilylacetylene addition of hetroaromatic, a,b-unsaturated aldehydes has attracted less attention yet.…”

Solvent-free Synthesis of Propargylic Alcohols using ZnO as a New and Reusable Catalyst by Direct Addition of Alkynes to Aldehydes

“…It is interesting to note that easily enolizable aldehydes (alkyl aldehydes C 3 -C 5 ) produced alkynylated products 3a-e with 95-98% yields and no aldol condensation by products were formed. Benzaldehyde derivatives having both electron-donating and withdrawing substituents, 2-naphthaldehyde, and a heterocyclic aldehyde gave the products in good to excellent yields (entries [6][7][8][9][10][11][12][13][14].…”

“…The alkynylation of carbonyl compounds is a direct chain extension reaction. [1][2][3][4][5][6][7][8] Propargylic alcohols are important and versatile building blocks for many biologically active compounds and natural products such as adociacetylene B, 9 longimicin D, 10 leukotriene B 4 , 11 steroid, 12 prostaglandins, 13 and carotenoids, 14 and have gained considerable attention in recent years. The most common methods to obtain propargylic alcohols are the nucleophilic addition of stoichiometric amounts of strong bases such as organolithium, dialkyl zinc or organomagnesium reagents with or without Lewis acids.…”