Highly regioselective additions of certain 2-lithio-1,3-dithianes to conjugated ketones

Polymer-Supported Synthesis of α- and β-Hydroxyketones through the Formation of 1,3-Dithiane Intermediates

“…The reaction of P2Lia with the enone h producing P5ah was carried out under thermodynamic control working at room temperature 11 or in the presence of HMPA, 12 under kinetic control operating at -75°C, 11 and quenching the process with cooled water-methanol.…”

“…To shed light on the process, compound 12 (Figure 1) was prepared 11 as a model for the 1,4-addition, and made to re-act with the mercury reagent. The reaction afforded a mixture of 6ah (67%) and 7ah (22%) only, proving the occurrence of 1,4-addition reaction without the 1,2-addition in the synthesis of P5ah under thermodynamic control.…”

The Regioselectivity of Addition of Organolithium Reagents to Enones and Enals: The Role of HMPA

“…The addition chemistry to α,β-unsaturated carbonyl compounds can only be of practical synthetic utility if one of the two regioisomers is generated selectively. The synthetic importance of these reactions is reflected by the extensive efforts directed toward elucidating the effects that changes in solvent, temperature, and steric bulk as well as main group and transition metal additives have on the regioselectivity of addition of organolithium reagents to enones and enals. ,− …”

“…The first demonstration that the 1,4:1,2 ratio could in some cases be controlled by proper choice of temperature or solvent appeared in 1977, when it was found that the kinetic preference for 1,2 addition by metalated 2-phenyl-1,3-dithiane could be overcome by performing the reaction at higher temperatures and in more polar solvent, leading to the thermodynamically favored 1,4 product. A year later, for a reaction determined to be entirely under kinetic control, the opposite temperature dependence was observed: lower temperatures favored the 1,4 product and higher temperatures favored the 1,2 product .…”

“…The synthetic importance of these reactions is reflected by the extensive efforts directed toward elucidating the effects that changes in solvent, temperature, and steric bulk as well as main group and transition metal additives have on the regioselectivity of addition of organolithium reagents to enones and enals. 2, [7][8][9][10][11][12][13][14][15] The first demonstration that the 1,4:1,2 ratio could in some cases be controlled by proper choice of temperature or solvent appeared in 1977, 7 when it was found that the kinetic preference for 1,2 addition by metalated 2-phenyl-1,3-dithiane could be overcome by performing the reaction at higher temperatures and in more polar solvent, leading to the thermodynamically favored 1,4 product. A year later, for a reaction determined to be entirely under kinetic control, the opposite temperature dependence was observed: lower temperatures favored the 1,4 product and higher temperatures favored the 1,2 product.…”