In the typical procedure in the Experimental Section of this paper (see also the Supporting Information), the first sentence should read: "The aryl iodide (1.05 mmol) was dissolved in Et 2 O (0.5 mL) under an inert atmosphere and cooled to À55 8C before the addition of nBuLi (1.05 mmol, 656 mL, 1.6 m in hexanes)." The authors apologize for the oversight.
JP4-039 is a novel nitroxide conjugate capable of crossing lipid bilayer membranes and scavenging reactive oxygen species (ROS). An efficient and scalable one-pot hydrozirconation-transmetalation-imine addition methodology has been developed for its asymmetric preparation. Furthermore, this versatile methodology allows for the synthesis of cyclopropyl and fluorinated analogs of the parent lead structure.
Aiming to enlarging the scope of potential Michael acceptors in the copper-catalyzed asymmetric conjugate addition, [1, 2] we regarded the class of a-halo enones as being attractive, because the resulting a-halo ketones are versatile intermediates that are widely used in organic synthesis, for example, in the synthesis of a variety of heterocycles, [3] in cross aldol condensations, [4] in the synthesis of enaminoketones, [5] and in Favorskii rearrangements.[6] Of particular interest was the reactivity of the resulting a-halogenated enolate, which could be seen as a carbenoid that might undergo inter-or intramolecular cyclopropanation reactions in the presence of a copper catalyst (Scheme 1). [7] There are scarce examples of the conjugate addition of allyllithium, [8] cuprates, [9] or organometallic reagents that react under copper catalysis, such as Grignard [10e] and organozinc reagents, [11] to a-halogenated Michael acceptors. However, no results have been reported so far for the asymmetric conjugate addition of dialkyl zinc or trialkyl aluminum reagents to a-halo enones, despite all the recent progress in this research area.[1b] We describe herein the results of our research on this topic, including an interesting observation of an improvement in enantioselectivity when styrene is employed as a radical scavenger.With respect to the proposed reaction in Scheme 1, there were three main points to address: 1) the reactivity of a-halo enones, 2) the level of enantioselectivity that could be attained in an enantioselective process, and 3) the feasibility of the cyclopropanation. First, we compared the reactivity of the a-halo cyclohexenones 1-3 (Scheme 2) with that of cyclohexenone. The conjugate addition reactions carried out in parallel in the presence of Et 2 Zn and ligand L4 (see details in the Supporting Information) showed that a-halogenated enones were less reactive than cyclohexenone and that the reactivity of the three substrates 1, 2, and 3 decreased mildly with increasing electronegativity of the halogen (Scheme 3).
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