Catalytic Asymmetric Boration of Acyclic α,β‐Unsaturated Esters and Nitriles

Abstract

Organoboranes are versatile synthetic intermediates for the preparation of a wide range of organic molecules. An increasing effort has been devoted to the efficient synthesis of organoboron compounds. One of the important tools for the synthesis of organoboranes is transition-metal-catalyzed addition of diboron reagents such as bis(pinacolato)diboron to carbon-carbon multiple bonds, which has been the subject of extensive research.[1] In comparison with electron-rich alkene or alkyne substrates, the reaction with a,b-unsaturated carbonyl compounds has not been studied as extensively. Since introducing a boronate group at the b-position to a carbonyl using conventional hydroboration methods is not possible, the metal-catalyzed b-boration of a,b-unsaturated carbonyl compounds provides an interesting approach. Such reactions have been reported using systems based on platinum, [2] rhodium, [3] and copper [4] but with limitations such as high catalyst loading, high temperature, low to moderate yield, and narrow substrate scope.Recently, we reported an efficient copper-catalyzed addition of bis(pinacolato)diboron (B 2 pin 2 ) to a range of a,b-unsaturated carbonyl compounds, the substrate scope of which was extended from enones to more challenging a,bunsaturated esters, nitriles, and phosphonates. [5] In view of the variety of stereospecific transformations available to stereogenic carbon-boron bonds, [6] we envisioned that catalytic enantioselective boration of a,b-unsaturated carbonyl compounds would easily provide functionalized enantioenriched organoboron compounds. However, an asymmetric boration of such compounds has not been reported yet. Herein, we describe the enantioselective b-boration of a,b-unsaturated esters and nitriles catalyzed by a nonracemic copper phosphine complex.In our previous study on the copper-catalyzed b-boration, we found that both a suitable ligand and methanol additive were required for complete conversion. Especially the alcohol was critical to the enhanced rate of reaction; even a reaction with no ligand proceeded with great conversion in the presence of methanol. Because this methanol effect could be deleterious to enantioselectivity, minimizing the background reaction would be the key for the successful development of an asymmetric variant of the b-boration.In preliminary experiments, we chose cinnamonitrile as a model substrate and (R)-(S)-josiphos (L1, Scheme 1) as a nonracemic ligand on the basis of its successful use in the asymmetric reduction of acrylonitriles, [7] and we examined a range of reaction conditions. Variable enantiomeric excesses (50-85 % ee) were obtained without reproducibility when a 1:1 combination of CuCl and NaOtBu was employed. We surmised that insufficient reaction of the two inorganic salts in THF, an inadvertent shortage of the nonracemic ligand relative to copper, or a combination of these two factors might increase the concentration of catalytic species that cause nonselective reactions. Increasing the amount of base to 1.5 equivalents relative to copper...

Highly Enantio‐ and Diastereoselective Synthesis of γ‐Amino Alcohols from α,β‐Unsaturated Imines through a One‐Pot β‐Boration/Reduction/Oxidation Sequence

“…[8] Particularly, copper(I) complexes modified with chiral phosphine ligands can activate tetraalkoxydiborane reagents to promote the selective addition of the dialkoxyboryl group to the b-position of a,b-unsaturated carbonyl compounds. [9] For further functionalization, conventional oxidation of the C À B(OR) 2 function to C À OH occurs with complete retention of configuration. Alternatively, nickel and palladium complexes modified with chiral ligands, can also catalyze the bboration reaction providing enantioenriched a-chiral boron compounds, [10] and opening new possibilities for tandem catalytic cross-coupling reactions.…”

Synthesis of syn and anti 1,4‐Diols by Copper‐Catalyzed Boration of Allylic Epoxides

“…[8] Chiral organoboron compounds are versatile synthetic intermediates for the preparation of a wide range of organic molecules. Recently, copper-catalyzed borations of a,b-unsaturated carbonyl compounds [9] and allylic carbonates [10] have emerged as an important tool for the synthesis of enantiopure organoboron compounds. In this context, copper-catalyzed S N 2' addition of diboronates to allylic epoxides (Scheme 1) is a potentially powerful transformation for the formation of 2-ene-1,4-diols I via the corresponding 1,4-hydroxyboronates II.…”

Conjugate Boration of β,β‐Disubstituted Unsaturated Esters: Asymmetric Synthesis of Functionalized Chiral Tertiary Organoboronic Esters

“…[10] Along with alkenyl boron derivatives, the use of alkyl boron derivatives as sp 3 -hybridized carbon nucleophiles has recently increased, [11] and notable examples of stereoretentive coupling reactions of chiral alkyl boron derivatives have recently been reported by Crudden [12] and Aggarwal. [13] In this regard, the feasibility of using our chiral tertiary organoboron product 3 a as a carbon nucleophile possessing an ester functionality was tested for the first time in a rhodium-catalyzed addition reaction under Aggarwals conditions (Scheme 2).…”

“…Josiphos and BINAP led to very poor conversions, while chiral phosphine ligands with a short tether between the two phosphines showed comparable reaction conversions (entries [3][4][5]. The optimal ligand was determined to be MeDuphos, which resulted in complete conversion to the product with excellent [a]…”