587 Pure Appl. Chem., Vol. 83, No. 3, pp. 587–596, 2011. doi:10.1351/PAC-CON-10-10-24 © 2011 IUPAC, Publication date (Web): 3 February 2011 Specific conjugate addition to ,-acetylenic ketones* Myagmarsuren Sengee and Leiv K. Sydnes ‡ Department of Chemistry, University of Bergen, Allégt. 41, NO-5007 Bergen, Norway Abstract: A variety of α,β-unsaturated acetylenic ketones, prepared in good yields from 3,3,4,4-tetraethoxybut-1-yne (TEB), have been reacted with selected mono- and bis-nucleo- philic reagents. The mononucleophiles react in a Michael fashion and give in most cases the corresponding α,β-unsaturated alkenones in good yield. Many of the alkenes are formed as single stereoisomers, but the configuration depends on the nature of the nucleophile. If hydrogen bonds can be formed, the Z geometry is preferred, otherwise the E geometry is completely predominant. Experiments have also uncovered that α,β-unsaturated acetylenic ketones with a gem-diethoxy moiety in the α' position decompose when reacted with sodium hydroxide in aqueous tetrahydrofuran (THF); the carbonyl group is attacked and a carboxylic acid and a terminal alkyne are formed. If the nucleophiles contain two nucleophilic centers or if the α,β-unsaturated acetylenic ketones contain an additional reactive group, such as a hydroxyl group or an acyloxy moiety, useful secondary reactions may occur. By taking advantage of such secondary transforma- tions, two completely regioselective syntheses of furans have so far been developed. Keywords: amine addition; conjugate addition; conjugated alkenones; dialkylcuprates; 1,3-dithiane; regiospecific transformations; tetrasubstituted furans; thiolate addition; tri- substituted furans. INTRODUCTION When a synthetic method was developed that made 3,3,4,4-tetraethoxybut-1-yne (TEB) easily available in large quantities [1,2], a program was launched to explore the chemical potential of this highly func- tionalized molecule. Among the studies in progress is an investigation of the ability of α,β-unsaturated acetylenic ketones to react with a range of nucleophiles. So far, the study has focused on three groups of ketones. The simplest one consists of one compound only, viz. 1,1-diethoxybut-3-yn-2-one (1), which is obtained in good yield by exposing TEB to slightly acidic conditions [3]. The second group consists of γ-hydroxylated α,β-unsaturated acetylenic ketones (2) (synthesized by TEB-acetylide cou- pling with a range of aldehydes followed by deketalization), whereas the third is comprised of a vari- ety of 5-acyloxy-1,1-diethoxyalk-3-yn-2-ones (3) (prepared by TEB-acetylide coupling with a range of aldehydes, followed by esterification, and completed by deketalization) (Scheme 1) [4]. Regarding the nucleophiles the focus has so far been mostly on thiolates, alcohols, amines, and dialkyl cuprates, and the results presented here will therefore be limited to these nucleophilic species. *Paper based on a presentation made at the 18 th International Conference on Organic Synthesis (ICOS-18), Bergen, Norway, 1–6 August 2010. Other presentations are published in this issue, pp. 411–731. ‡ Corresponding author: E-mail: leiv.sydnes@kj.uib.no