Copper-mediated asymmetric transformations

Abstract

Copper-catalyzed reactions include the enantioselective conjugate addition and the S N 2′ substitution. We describe the genesis of these reactions, the choice of the primary organometallic reagent, and our studies on finding new Michael acceptors and new ligands. We also report on the use of the zinc enolate generated upon conjugate addition.

Rhodium‐ and Palladium‐Catalyzed Asymmetric Conjugate Additions

“…It is important to note, that potassium organotrifluoroborates do not transmetallate directly to rhodium(I), but rather that a monohydroxyborate (20) is probably the boron species that effects the transmetallation step, with a mechanism akin to that depicted in Scheme 1.8. This monohydroxyborate (20) has been observed to be in equilibrium with the corresponding potassium organotrifluoroborates (19) (22) is also a very active reagent for the ECA, but is relatively unstable and is best formed in situ by lithium/halogen exchange on an aryl bromide, followed by addition of trimethoxyborane [31,45]. Cyclic aryl triolborates (23) are also convenient and reactive reagents for Rh-catalyzed ECAs [46,47]; these reagents have the advantage of being very stable in air and water, and more soluble in organic solvents than related potassium organotrifluoroborates.…”

“…Potassium aryltrifluoroborate salts (19) have become a very popular source of organoboron reagents [34][35][36], because they are more stable than the corresponding boronic acids while still being reactive in Rh-cat. ECAs [37].…”

“…For the first time, a wide range of aryl and alkenyl fragments could be added in high yields and with exquisite enantioselectivity to an α,β-unsaturated ketone using (S)-binap ((S)-L1) as the chiral diphosphine ligand (Scheme 1.2) [17]. Since this initial report, great progress has also been made in the copper-catalyzed ECA using Grignard and organozinc reagents (this subject is treated in detail in Chapter 3) [18][19][20][21]. In order to achieve such high enantioselectivities in the Rh-catalyzed ECA, several factors had to be modified from the original conditions: namely, the rhodium precursor was changed from [Rh(acac)(CO) 2 ] to [Rh(acac)(C 2 H 4 ) 2 ]; the solvent system was changed to 1,4-dioxane/H 2 O (10 : 1); the temperature was increased to 100 • C; and the reaction time was shortened to 5 h. The scope of the reaction was very broad, and a wide range of arylboronic acids (2) substituted with electron-donating or -withdrawing groups could be added to 2-cyclohexenone (1a) with high enantioselectivities (Scheme 1.2, entries 2-5).…”

Pincer Complexes of Lithium, Sodium, Magnesium and Related Metals: A Discussion of Solution and Solid-State Aggregated Structure and Reactivity

“…The complex (2,6-dimethoxyphenyl)lithium (22) exists as a tetramer of cubic (Fig. 3) structure [106,107].…”

“…Indeed, few total syntheses carried out today do not employ these classic reagents. In recent years, the milder (and often more selective) organocopper [21][22][23][24][25][26][27][28] and organozinc reagents [29][30][31][32][33][34][35] have become of widespread synthetic utility and accessibility. Given the rich history of the title elements in organic synthesis and organometallic chemistry in general, it is of little surprise that these elements have been investigated and utilised in the chemistry of the "pincer" ligands ( Fig.…”