Itsuno catalyst

Some of the above-mentioned catalysts or precursors are commercially available, such as the Corey catalyst (,S) - 3,3 - d i p h e n yI -1 - met h y 1 tctralr yd ro- 3 H - py r-rolo[l,2-c] [l,3,2]oxazaborole (Me-CBS). The amino alcohol (5)-(—)-2-amino-3-methyl-l,l -diphenylmethan-l-ol, used as the ligand in the Itsuno catalyst is also readily available. The ligand used to prepare the oxazaphospholidine or oxazaphosphinamide complex (from Wills) can be synthesized easily from commeri-cally available material. The preparation of the Bolm (3-hydroxysulfoximine catalyst will be described in this chapter (Figure 11.2). 

In a direct comparison of the reduction of acetophenone to highly enantio-en-riched (R)-phenylethanol (94% e.e.) by heterogenized (S)-diphenyloxazaborolidine (Corey-Itsuno catalyst) or to enantiomerically pure (S)-phenylethanol (> 99% e.e.) by Candida parapsilosis carbonyl reductase (CPCR), the superior solubility of acetophenone in THF (0.25 m) versus water (0.04 m) leads to a vastly superior space-time yield of 290 g (L d) 1 in THF with the Corey-Itsuno catalyst in comparison with 27 g (L d) 1 in water with CPCR (Rissom, 1999). Conversely, the turnover frequencies (tofs) of 0.3 min-1 (Corey-Itsuno catalyst) versus 2.3 x 104 min-1 (CPCR) portend the difference in total turnover number (TTNs) of 2.4 x 108 versus 560. 

Acyloxyboron complexes and oxazaborolidines have been shown to catalyse Diels-Alder reactions featuring aldehydes as one component for example, the complex (51) allows the coupling of cyclopentadiene and a-bromoacrolein in high yield to give a product of high optical purity (Scheme 46)[132]. The immobilized catalyst system of this genre, recently introduced by Itsuno, is... 

Bentley et al.m recently improved upon Julia s epoxidation reaction. By using urea-hydrogen peroxide complex as the oxidant, l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) as the base and the Itsuno s immobilized poly-D-leucine (Figure 4.2) as the catalyst, the epoxidation of a, (3-unsaturated ketones was carried out in tetrahydrofuran solution. This process greatly reduces the time required when compared to the original reaction using the triphasic conditions. 

In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

When considering the easy recovery and reuse of chiral catalysts, or simple separation process of the product from chiral catalyst, polymer-supported catalysts are very attractive [1,3]. For the enantioselective ethylation using dialkylz-inc, Frechet and Itsuno s group and our group developed polystyrene-supported amino alcohols [1]. 

In other reports, /i-cyclodcxtrins have been used to induce asymmetry in borohydride reduction of ketones,166 a diastereoselective reduction has been controlled167 by a real lyltricarbonyl iron lactone tether , a phosphinamide has been combined with a dioxaborolidine unit as an activated, directed catalyst for ketone reduction,168 reductive amination using benzylamine-cyanoborohydride converts 3-hydroxy ketones into syn-1,3-amino alcohols,169 l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propan-l-one has been reduced diastereoselectively,170 and production of chiral alcohols via (i) Itsuno-Corey and Brown procedures171 and (ii) lithium aluminium hydride modified by chiral nucleophiles172 has been reviewed. 

S. Itsuno, M. Sakakura, and K. Ito, Polymer-supported poly(amino acids) as new asymmetric epoxidation catalyst of a,)3-unsaturated ketones, J. Org. Chem. 

The organocatalytic enantioselective reduction of C=C, C=0, and C=N double bonds is a relatively young area for which many new and exciting developments can be expected in the near future. Hantzsch esters are useful organic hydrides, and a recent review has summarized the results obtained to date in organocataly-sis [27]. The case of silicon hydrides is convenient for imine or ketone reductions, as a chiral base can act as an organic catalyst. The asymmetric reductions of ketones catalyzed by oxazaborolidines and pioneered by Itsuno [28] and Corey [29] could not be included in this chapter. 

The first enantioselective process within the flow domain was the reduction of valerophenone (5) by borane in the presence of the polymer-supported amino alcohol catalyst 6 (Scheme 4.52) as reported by Itsuno [100]. Solutions of 5 and borane were mixed into the bottom of the column using long syringe needles, and the product 7 flowed from the top. Following washing with TH F and water, acidic workup and bulb-to-bulb distillation, 1.8 g of 7 was isolated in 84% yield and in 83-91% ee, depending on the fraction analyzed. 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

Kumagai, T., Itsuno, S. Asymmetric Aiiyiation Polymerization Novel Polyaddition of Bis(allylsilane) and Dialdehyde Using Chiral (Acyloxy)borane Catalyst. Macromolecules 2000, 33,4995-4996. 

Itsuno et al. have reported the use of polymer-supported oxazaborolidinone 102 as a chiral catalyst for asymmetric Diels-Alder reactions (Scheme 17)... 

Prolinol or diphenylprolinol were found by Corey et al. [87] and Itsuno et al. [88] to catalyze the enantioselective diborane reduction of many ketones. Corey et al. developed this new route greatly, often called CBS reduction (from the names of the authors of Ref. [87]). An oxazaborolidine which is either formed in situ or can be preformed, is the actual catalyst. A mechanistic picture has been proposed [87]. 

The choice of the best method seems to depend on the catalytic system. A comparison of immobilized catalysts for enantioselective hydrogenation shows a clear superiority of the catalysts that were prepared by grafting. On the other hand, Itsuno [23] found that immobilized Lewis acid catalysts for Diels-Alder reactions showed better performance when they were prepared by copolymerization. 

Most recent research has been focused on the application of polymers as chiral auxiliaries in enantioselective Lewis-acid-catalyzed reactions. Studies of Itsuno and co-workers [44] culminated in the development of a polymer-supported catalyst containing a chiral oxazaborolidinone with oxyethylene crosslinkages which gave the Diels-Alder adduct of cyclopentadiene and methacrolein in 88 % isolated yield with an exotendo ratio of 96 4 and 95 % e. e. for the exo adduct. A variety of polymer-supported chiral Lewis acids was also investigated by Mayoral et al. [45]. Some supported catalysts were more active than their homogeneous analogs, but enantioselectivity was always lower. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

E. J. Corey, C. J. Helal, Angew. Chem. 1998, 110, 2092 Angew. Chem. Int. Ed. 1998, 37, 1986 (Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method.), S. Itsuno, in Organic Reactions , Ed. L. A. Paquette, John Wiley Sons, New York, 1998, Vol. 52, pp. 395-576 (Enantioselective Reduction of Ketones). 

One of the more widely used solutions to this challenge is the chiral borohydride analogue invented by Itsuno in Japan and developed by Corey, Bakshi, and Shibata. It is based on a stable boron heterocycie made from an amino alcohol derived from proline (see the box below for the synthesis), and is known as the CBS catalyst after its developers. The active reducing agent is generated when the heterocycie forms a complex with borane. Only catalytic amounts (usually about 10%) of the boron heterocycie are needed because borane is sufficiently reactive to reduce ketones only when complexed with the nitrogen atom. The rest of the borane just waits until a molecule of catalyst becomes free. 

Polymeric Chiral Catalyst Design and Chiral Polymer Synthesis, ed. S. Itsuno, John Wiley Sons, 2011. 

Recently, Sirit and co-workers [45] developed calixarene-based chiral phase-transfer catalysts derived from cinchona alkaloids successfully used for alkylation of glycine-imine esters. In 2010, Itsuno et al. [46] published quartemary ammonium sulfonate polymers used for a-alkylation reaction of a glycine imine ester with high yields and enantioselectivity. 

In addition, in 2(X)4 Mamoka and co-workers [72] synthesized a recyclable fluorous chiral phase-transfer catalyst which was successfully applied for the catalytic asymmetric alkylation of a glycine-imine derivative followed by extractive recovery of the chiral phase-transfer catalyst using fluorous solvent. Later, in 2010 Itsuno and co-workers [73] published a new type of polymer-supported quarternary ammonium catalysts based on either cinchona alkaloids or Maruoka s-type catalyst bound via ionic bonds to the polymeric sulfonates. 

Itsuno, S., Sakurai, Y., Ito, K., Maruyama, T., Nakahama, S., and Frechet, J.M.J. (1990) New solid-phase catalysts for asymmetric synthesis cross-linked polymers containing... 

The past fifteen years witnessed the development of oxazaborolidines as catalysts for various organic reactions (44). The Itsuno-Corey asymmetric reduction is a prominent example (Figure 12) (45, 46). This chemistry led... 

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