Enantioselective Rhodium‐Catalyzed Addition of Arylboronic Acids to α‐Ketoesters

Abstract

The transition-metal-catalyzed asymmetric addition of organometallic reagents to carbonyl compounds to produce enantiomer-enriched secondary or tertiary alcohols is a powerful tool for the construction of carbon-carbon bonds. Many organometallic reagents have been successfully used in this addition reaction.[1] However, a drawback for most organometallic reagents is their sensitivity to moisture and air, both of which impede the practical applications of these asymmetric carbon-carbon bond-forming reactions. As an exception, arylboronic acids are very stable to air and moisture. The catalytic enantioselective addition of arylboronic acids to carbonyl compounds has became a current focus for research, [1d] and a number of efficient chiral catalysts have been developed for the catalytic asymmetric addition of arylboronic acids to aldehydes [2] and aldimines.[3] However, the catalytic asymmetric addition of arylboronic acids to ketones, which are less active relative to aldehydes and aldimines, is more difficult, and only limited progress has been achieved. In 2006, Hayashi et al. reported the asymmetric addition of arylboronic acids to isatins, cyclic aketoamides, catalyzed by a rhodium/MeO-Mop (MeO-Mop = 2-methoxy-2'-diphenylphosphino-1,1'-binaphthyl) complex in high enantioselectivities (72-91 % ee).[4] By using a chiral phosphoramidite ligand derived from H 8 -binol (binol = 2,2'-dihydroxy-1,1'-binaphthyl), de Vries, Minnard, Feringa and et al. obtained 55 % ee in the same reaction.[5] The chiral phosphoramidite ligand was also used in the asymmetric addition of arylboronic acids to trifluoromethyl ketones with good enantioselectivities (50-83 % ee).[6] The intramolecular asymmetric addition of arylboronic acids to ketones catalyzed by a cationic palladium complex of binap (binap = 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl) to give cyclic tertiary alcohols in high enantioselectivities (53-96 % ee) was reported by Lu et al. [7] To the best of our knowledge, the catalytic enantioselective addition of arylboronic acids to aketoesters to provide tertiary a-hydroxyesters has not yet been reported. [8] In the search for highly efficient methods to construct chiral 2-hydroxydiarylacetates, desirable chiral intermediates for the synthesis of antagonists of muscarinic receptors, [9] we became interested in the enantioselective addition of arylboronic acids to the a-aryl-and a-alkenyl-a-ketoesters. The Rh I /ShiP (ShiP = aryl(1,1'-spirobiindane-7,7'-diyl)phosphite) catalysts (1) recently developed by us [2c, 3b] were found to be highly efficient for this addition reaction to provide chiral tertiary a-hydroxyesters [10] in good yields and high enantiomeric excesses (up to 93 % ee).Preliminary experiments were carried out in H 2 O with catalyst generated in situ from 1.5 mol % [{RhCl-(CH 2 CH 2 ) 2 } 2 ][11] and 6 mol % (S)-1 a in the presence of two equivalents of LiF.[12] The addition of phenylboronic acid to ethyl 2-(4-chlorophenyl)-2-oxoacetate (2 a) at room temperature for 48 hours afforded tertiary a-hydroxyeste...

Towards the Synthesis of the 4,19‐Diol Derivative of (–)‐Mycothiazole: Synthesis of a Potential Key Intermediate

“…The advantage of compound 4 is its possible selective cleavage by hydrogenolysis and its ability to perform π-stacking with aromatic chiral auxiliaries in the case of asymmetric dihydroxylation, as reported by Oi and Sharpless. [15] The construction of the second fragment 6 could be achieved by condensation of 2,2-dimethylpropanediol (7) and cysteine (8) followed by aromatization of the resulting thiazolidine and a few straightforward functional group manipulations. As shown in Scheme 1, our initial approach to building subunit 3 started from commercially available dimethyl itaconate (5).…”

“…A nonexhaustive survey of the literature showed that the 1,1-dialkyl-1,2-ethanediol motif is present in relatively few natural products, the total syntheses of which, in general, have not yet been described. [7] Nevertheless, some methods have been published in the literature that give access to such a group, for example, by addition of a phenylboronic acid to an α-keto ester catalyzed by rhodium, [8] by addition of an alcohol to a vinyl epoxide in the presence of a catalytic amount of trialkylborane and palladium, [9] or by rearrangement of 2-(1-hydroxyalkyl)-1-cyclopropanols using organozinc catalysis. [10] The classical dihydroxylation of double bonds [11] or reduction of hydroxy esters [12] can also be used.…”

Axially chiral C2-symmetric N-heterocyclic carbene (NHC) palladium complexes-catalyzed asymmetric arylation of aldehydes with arylboronic acids

“…It was found that no reaction occurred in the absence of base, even when the reaction was carried out at 60°C (Table 1, entries 1-3). Base screening for the reaction revealed that using KOH (1.0 equiv) as the base afforded 8aa in 48% ee and >99% yield in CHCl 3 and increasing or decreasing the employed amount of KOH did not improve the yield of 8aa (Table 1, entries [4][5][6]. The other bases such as KF, K 3 PO 4 , H 2 O, KO t Bu, Cs 2 CO 3 , Ag 2 CO 3 , and NaOH did not give 8aa in good yields (Table 1, entries 7-13).…”

“…4 Among these synthetic methods, Zhou et al developed several novel and effective chiral Rh-spiromonophosphite complexes for this reaction, achieving 62-87% ees along with good yields for representative aromatic aldehydes. 5 More recently, Miyaura et al have developed an interesting Me-bipam ligand system for the enantioselective ruthenium-catalyzed arylation of aldehydes with arylboronic acids, affording the corresponding diarylmethanols in good yields and ees. 6 Hayashi et al also have developed effective tbf ligands for the rhodium-catalyzed asymmetric arylation of aldehydes, giving chiral diarylmethanols in high yields and ees.…”

Asymmetric catalytic arylation of ethyl glyoxylate using organoboron reagents and Rh(i)–phosphane and phosphane–phosphite catalysts

“…1f, 17 The results are shown in Table 2. Generally, moderate to excellent yields were obtained with [RhCl(C 2 H 4 ) 2 ] 2 (see Table 2, entries 3, 4, 8, 10 and 12).…”