Shibasaki direct catalytic asymmetric

Y. M. A Yamada, N. Yoshikawa, H. Sasai, M. Shibasaki, Direct Catalytic Asymmetric Aldol Reactions of Aldehydes and Unmodified Ketones, Angew. Chem. Int. Ed EngL 1997, 36,1871-1873. 

Recent example, see L. Yin, H. Takada, S. Lin, N. Kumagai, M. Shibasaki, Direct catalytic asymmetric vinylogous conjugate addition of unsaturated butyrolactones to a,f5-unsaturated thioamides, Angew. Chem. Int. Ed. 53 (2014). http //dx.doi.org/10.1002/anie.201402332. 

SCHEME 836. The Shibasaki direct catalytic asymmetric aldol reaction using LLB. 

The capability of L-proline - as a simple amino acid from the chiral pool - to act like an enzyme has been shown by List, Lemer und Barbas III [4] for one of the most important organic asymmetric transformations, namely the catalytic aldol reaction [5]. In addition, all the above-mentioned requirements have been fulfilled. In the described experiments the conversion of acetone with an aldehyde resulted in the formation of the desired aldol products in satisfying to very good yields and with enantioselectivities of up to 96% ee (Scheme 1) [4], It is noteworthy that, in a similar manner to enzymatic conversions with aldolases of type I or II, a direct asymmetric aldol reaction was achieved when using L-proline as a catalyst. Accordingly the use of enol derivatives of the ketone component is not necessary, that is, ketones (acting as donors) can be used directly without previous modification [6]. So far, most of the asymmetric catalytic aldol reactions with synthetic catalysts require the utilization of enol derivatives [5]. The first direct catalytic asymmetric aldol reaction in the presence of a chiral heterobimetallic catalyst has recently been reported by the Shibasaki group [7]. 

Shibasaki and coworkers have conducted extensive research on the use of hetero-bimetallic complexes as catalysts for asymmetric synthesis [11]. The reactions are catalyzed by heterobimetallic complexes that function as both a Lewis acid and a Bronsted base. Among these, LaLi3tris(binaphthoxide) catalyst 1 (LLB) was proven to be an effective catalyst in direct asymmetric aldol reactions (Fig. 1) [12]. On the basis of this research, Shibasaki et al. reported the first report of a direct catalytic asymmetric Mannich reaction [13],... 

Yamada YM, YoshikawaN, SasaiH, Shibasaki M (1997) Direct catalytic asymmetric aldol reactions of aldehydes with unmodified ketones. Angew Chem Int Ed Engl 36 1871-1873... 

Matsunaga S, Kumagai N, Harada S, Shibasaki M (2003) anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols. J Am Chem Soc 125 4712—4713 Mayer S, List B (2006) Asymmetric counteranion-directed catalysis. 

A possible way to induce enantioselectivity in the aldol reaction is to empioy a chirai catalyst. M. Shibasaki and coworkers developed a bifunctional catalyst, (S)-LLB (L=lanthanum LB=lithium binaphthoxide), which could be successfully applied in direct catalytic asymmetric aldol reactions. An improved version of this catalyst derived from (S)-LLB by the addition of water and KOH was utilized in the formal total synthesis of fostriecin. ... 

Shibasaki, M., Yoshikawa, N., Matsunaga, S. Direct catalytic asymmetric aldol reaction. Comprehensive Asymmetric Catalysis, Supplement 2004, 1, 135-141. 

Although the development of a range of catalytic asymmetric aldol-type reactions has proven to be a valuable contribution to asymmetric synthesis [35—37], in all of these reactions pre-conversion of the ketone moiety to a more reactive species such as an enol silyl ether, enol methyl ether, or ketene silyl acetal has been an unavoidable necessity. However, quite recently Shibasaki et al. reported that a direct catalytic asymmetric aldol reaction, which is known in enzyme chemistry, is also possible in the presence of heterobimetallic lanthanoid catalysts [38]. Using fR)-LLB (20 mol%), which shows both Lewis acidity and Bron-sted basicity similar to the corresponding aldolases, the desired optically active aldol adducts were obtained with up to 94% ee. A variety of aldehydes and unmodified ketones can be used as starting materials (Scheme 11). 

In the field of zinc-catalyzed aldol reaction, Shibasaki s group also gave important contribution, especially in the development of a highly efficient zinc/linked BINOL complex as a mimic of zinc metalloenzymes for direct catalytic asymmetric aldol reactions (111,112). The structure of Shibasaki s Zn... 

At the time these relatively modest results represented the state-of-the-art in direct catalytic asymmetric aldolizations with a-unbranched aldehyde acceptors. Neither Shibasaki s nor Trost s bimetallic catalysts, the only alternative catalysts available, gave superior results. Moreover, even non-asymmetric amine-catalyzed cross aldolizations with a-unbranched acceptors are still unknown. That the practicality of the process can compensate for the modest yield and enantioselectivity was illustrated by a straightforward synthesis of the natural pheromone (S)-ipsenol (139) from aldol 136d, featuring a high-yielding Stille coupling (Scheme 4.27). 

In 1999, Shibasaki et al. reported on the direct catalytic asymmetric aldol reaction (Scheme 8.36), which was not necessary to preconvert the ketone moiety into the more reactive species such as an enolate ion and enol ether." The addition of bulky aldehyde 248 into the mixture of ethyl methyl ketone 249 and LaLi3tris(/ -binaphthoxide) [(/ )-LLB)] afforded aldol adduct 250 in excellent stereoselectivity. However, this reaction required a large amount of ketones (50 equiv), and catalyst (20 mol%) were required. They improved the conditions to reduce the amount of ketone (5 equiv) and catalyst (8 equiv) by using the hetero-polymetallic asymmetric catalyst (Scheme 8.37). The addition of the catalytic amount of potassium bis(trimethylsilyl) amide (KHMDS) and H2O was found to be effective to the catalysis. Adduct 253 was converted into ester 254 by the... 

Iwata M, Yazaki R, Kumagai N, Shibasaki M. Direct catalytic asymmetric aldol reactions of thioamides toward a stereo-controlled synthesis of 1,3-polyols. J. Am. Chem. Soc. 2009 131(51) 18244-18245. 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

Shibasaki and co-workers have reported the first catalytic asymmetric aldol reaction between aldehydes and unmodified ketones by using heterobimetallic multifunctional catalysts. Later, Trost and co-workers reported the direct... 

Harada S, Kumagai N, Kinoshita T, Matsunaga S, Shibasaki M (2003) Direct catalytic as3Tnmetric Michael reaction of hydroxyketones asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. J Am Chem Soc 125(9) 2582-2590. doi 10.1021/ja028928+... 

Shibasaki et al. reported on a direct awri-selective catalytic asymmetric Mannich-type reaction of a-ketoanilides 191122 puj- ermore, they transformed the anti Mannich adduct 192 into a-hydroxy-y-amides 193, which under asymmetric alkylative cyclization produces azetidine-2-amides 194 in good yield and excellent stereoselectivity (Scheme 40.40). 

Xu Y, Lu G, Matsunaga S, Shibasaki M. Direct anti-selective catalytic asymmetric Mannich-type reactions of a-ketoanilides for the synthesis of -Y-amino amides and azetidine-2-amides. Angew. Chem. Int. Ed. 2009 48(18) 3353 3356. 

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