Addition of aminoketene dithioacetals to α,β-unsaturated ketones. Synthesis and reactions of cyclohex-2-en-1,4-dione monodithioacetals

Chemoselectivity as a Delineator of Cuprate Structure in Catalytic 1,4‐Addition of Diorganozinc Reagents to Michael Acceptors

“…This behavior was identical when copper(I)thiothene carboxylate (TC) [Cu(TC)] [15] or CuA C H T U N G T R E N N U N G (OAc) 2 were used as precatalysts. Equivalent ZnMe 2 /Cu I /L A -mediated reaction of 1 b gave a product that was identical in every way to the product that results from the reaction of 1 b and LiCuMe 2 as described by Page et al [12] Based on 1 H NMR and IR spectroscopic data alone these authors had assigned the 1,2-addition structure 7 to this product. We believe this is a structural misassignment of compound 6 for the following reasons:…”

“…[11] In our hands, following the six-step procedure by Page et al [12] for 1 b gave the product, although one ZnCl 2 -promoted step was capricious (as Page had noted), which limited our overall yields to < 10 %. Unfortunately, 1 b was not available from reaction of 1 a with 1,3-propane dithiol under all conditions attempted.…”

“…Scheme 2. Literature [11,12] proposed reactivity for dienones 1 a and b. Reactions of dienones 1 a and 1 b with carbon nucleophiles:…”

“…[11] In earlier work Page and coworkers suggested that 1 b reacts with LiCuMe 2 by giving an unexpected 1,2-addition product with stoichiometric cuprates. [12] We speculated that the p-complexes formed from 1 a and 1 b that deliver these two disparate products would be highly similar. Further, this common cuprate structure, related to C, must be able to accommodate the observed experimental behavior of both, 1 a and 1 b, providing a good test for the validity of any computationally-derived intermediates on the conjugate addition pathway.…”

“…We conceived that reaction of the monoenone dithioacetal 11 with ZnMe 2 might resolve this issue (Scheme 10). However, in practice 11 (also available through literature procedures [12] ) showed insufficient reactivity in copper(I)/L A -or copper(I)/L D -catalyzed addition of ZnMe 2 under all conditions tried. However, use of the more Lewis acidic AlMe 3 led to sole formation of 12 in > 95 % ee (optimal 60 % isolated yield by using L D ), whereas under identical conditions 1 b still afforded 6 as the sole product in 62 % isolated yield.…”