C₁‐Symmetric Rh/Phebox‐Catalyzed Asymmetric Alkynylation of α‐Ketoesters

Abstract

Catalytic asymmetric alkynylation of carbonyl compounds is one of the most efficient routes for the synthesis of optically active propargylic alcohols, which are useful and versatile building blocks for a variety of functionalized molecules, such as biologically active natural products.[1] In the initial stages of development of this transformation, stoichiometric amounts of metal reagents such as organolithium, organomagnesium, and diorganozinc compounds were used to increase the nucleophilicity of the alkyne and to prevent an undesired retro reaction. [1,2] In terms of atom economy, [3] however, the direct in situ generation of a metal alkynylide species from terminal alkynes using a catalytic amount of the metal reagent is highly desirable. Since the pioneering work by Carreira and co-workers, who utilized catalytic amounts of Zn(OTf) 2 , Nmethylephedrine, and Et 3 N, [4] several efficient methods for the catalytic asymmetric alkynylation of aldehydes have been developed using chiral Zn, [5] In, [6] Cu, [7] and Ru [8] catalysts.[9]In contrast to the substantial progress made with aldehydes, the development of a catalytic asymmetric alkynylation of ketones for the construction of a tetrasubstituted carbon center in an enantioselective manner has had limited success due to low reactivity, difficulty in obtaining enantiofacial differentiation, and the ease of the retro reaction as compared with aldehydes.[10] Jiang et al. succeeded in promoting the asymmetric alkynylation of a-ketoesters with broad substrate scope and high enantioselectivity (up to 94 % ee)[11a] by modifying Carreiras Zn system. [4] Later, Shibasaki and co-workers reported Cu catalysis of trifluoromethyl ketone with up to 52 % ee, [11b] and the Rh catalysis of an a-diketone reported by Chisholm and co-workers gave the product in 5 % yield with 20 % ee.[11c] Although the method of Jiang et al. is useful for accessing chiral propargylic alcohols, there remains much room for improvement because this system requires 20 mol % catalyst loading, 30 mol % of external amine base, and a rather high reaction temperature (70 8C).[11a] Herein, we report the catalytic asymmetric alkynylation of a-ketoester 1 using various aryl-and alkylsubstituted terminal alkynes 2 catalyzed by as little as 3 mol % of C 1 -symmetric Rh/Phebox complexes 3 i and 3 j (Figure 1) to afford the corresponding propargylic alcohols with greater than 99 % ee. Because the acetate ligand on the Rh complex acted as an internal base, the reactions proceeded at 25 8C without any additives. An indanyl substituent on the oxazoline ligand was effective for obtaining high enantioselectivity and, in most cases, the C 1 -symmetric complex gave better results than the C 2 -symmetric complex. The electronic tuning of the Rh complex was achieved by introducing a nitro group at the para position to Rh and greatly improved both the reactivity and selectivity of the reaction. Moreover, the Rh complex had unique chemoselectivity; it selectively reacted with a a-ketoester over an aldehyde, thus allowing...

Development of Pincer Catalysts with Selected Group 8～10 Metals

“…产率和对映体选择性 [41] . 此外, 在三氟丙酮酸乙酯与芳 香端炔的反应中, 这两个铑化合物的对映体选择性要高 于相关的(Phebox)Rh(OAc) 2 (H 2 O)化合物 [32] . [44] .…”

Electrophilic C–H activation of benzene with a Shilov-inspired rhodium(III) diimine complex

“…The [39,40], and Rh III (acac) (PPh 3 ) (OC(O) (C 6 H 4 OH) 2 (H 2 O) (acac ¼ acetoacetonate) [41]. There also exists mer-Rh(carboxylate) 2 (H 2 O) complexes with Phebox-type supporting ligands (Phebox ¼ 2,6-bis(2-oxazolinyl) phenyl [42,43]) that exhibit cis-intramolecular hydrogen bonding from each carboxylate ligand to the aquo ligand. The RheOH 2 bond length for 4 is longer than the RheOH 2 bond trans to the organometallic ligand in both 2 and 3.…”

Enantioselective Alkynylation of Trifluoromethyl Ketones Catalyzed by Cation‐Binding Salen Nickel Complexes

“…In contrast, there are fewer reports on the enantioselective alkynylation of trifluoromethyl ketones, as the high reactivity of these electron‐deficient electrophiles has led to significant challenges associated with facial selectivity. Although there have been some reports on the enantioselective variant of this transformation, they all suffer from significant drawbacks, such as high temperatures, large excesses of expensive reagents, or the use of precious, second‐row transition metals as catalysts (Figure b) –…”