Oxazaborolidine polymer-supported

Ketones [60], P-fimetionalized ketones [61] [62] and meso eylic imide [63] have been enantioselectively redueed using polymer-supported chiral sulfonamides in presence of boranes (NaBH4/Me3SiCl or BH3.SMe2), leading in situ to the eorresponding oxazaborolidine polymer-supported chiral sulphonamide 70 (Scheme 32). 

Y. Y. Chu, Y. Synthetic studies on d-biotin, part 6 an expeditious and enantiocontrolled approach to the total synthesis of d-biotin via a polymer-supported chiral oxazaborolidine-cata-lyzed reduction of meso-cyclic imide strategy. Synthesis 2003, 2155-2160. 

In reactions with polymer-bound catalysts, a mass-transfer limitation often results in slowing down the rate of the reaction. To avoid this disadvantage, homogenous organic-soluble polymers have been utilized as catalyst supports. Oxazaborolidine 5, supported on linear polystyrene, was used as a soluble immobilized catalyst for the hydroboration of aromatic ketones in THF to afford chiral alcohols with an ee of up to 99% [40]. The catalyst was separated from the products with a nanofiltration membrane and then was used repeatedly. The total turnover number of the catalyst reached as high as 560. An intramolecularly cross-linked polymer molecule (microgel) was also applicable as a soluble support [41]. 

Oxazaborolidines have been found to be a unique catalyst for asymmetric borane reduction of ketones and imines [35,36]. Coordination of BH3 to the nitrogen atom of 24 serves to activate BH3 as a hydride donor and to increase the Lewis acidity of the boron atom (Eq. 9). The Lewis acidity of the boron atom in the oxazaborolidine plays an important role in the reduction. Several types of polymer-supported oxazaborolidine have been reported and are considered to be polymer-supported boron-based Lewis acids. 

The first report of a polymer-supported oxazaborolidine appeared in 1985 [37]. The polymer-supported chiral ligand amino alcohol (27) was prepared by reaction of chlor-omethylated polystyrene resin and enantiopure amino alcohol 26 with a phenolic hydroxyl group (Eq. 10). Borane reduction of ketones by use of polymer-supported oxazaborolidines proceeded very smoothly to give the corresponding chiral alcohol in quantitative yield. For example, the reduction of butyl phenyl ketone afforded 1-phe-nylpentan-l-ol in 97 % ee (27, Eq. 11). This is somewhat higher than that obtained by... 

The above mentioned polymer-supported oxazaborolidines are prepared from polymeric amino alcohols and borane. Another preparation of polymer-supported oxazaborolidines is based on the reaction of polymeric boronic acid with chiral amino alcohol. This type of polymer can be prepared only by chemical modification. Lithiation of the polymeric bromide then successive treatment with trimethyl borate and hydrochloric acid furnished polymer beads containing arylboronic acid residues 31. Treatment of this polymer with (li ,2S)-(-)-norephedrine and removal of the water produced gave the polymer-supported oxazaborolidine 32 (Eq. 14) [41 3]. If a,a-diphenyl-2-pyrrolidinemetha-nol was used instead of norephedrine the oxazaborolidine polymer 33 was obtained. The 2-vinylthiophene-styrene-divinylbenzene copolymer, 34, has been used as an alternative to the polystyrene support, because the thiophene moiety is easily lithiated with n-butyl-lithium and can be further functionalized. The oxazaborolidinone polymer 37 was then obtained as shown in Sch. 2. Enantioselectivities obtained by use of these polymeric oxazaborolidines were similar to those obtained by use of the low-molecular-weight counterpart in solution. For instance, acetophenone was reduced enantioselectively to 1-phe-nylethanol with 98 % ee in the presence of 0.6 equiv. polymer 33. Partial elimination of... 

Not only polystyrene supports, also other polymer supports were used in the preparation of polymeric amino alcohol ligands for dialkylzinc alkylation. For example, a vinylferrocene derivative with A,N -disubstituted norephedrine was copolymerized with vinylferrocene [60]. This polymeric chiral ligand (53) was used in the ethylation of aldehydes with moderate activity. Brown has reported that chiral oxazaborolidines have catalytic activity in the addition of diethyl zinc to aldehydes [61]. Polymers bearing chiral oxazaborolidines 37 were also active in the reaction and result on moderate enantioselectivity (<58 % ee) [62]. Enantiopure a,a -diphenyl-L-prolinol coupled to a copolymer prepared from 2-hydroxyethylmethacrylate and octadecyl methacrylate... 

The same reaction has also been catalyzed by chiral oxazaborolidinones derived from amino acids and boranes. They proved to be efficient catalysts for enantioselec-tive Diels-Alder reaction [91,92]. The polymer-supported chiral oxazaborolidinones 75 were reported to be efficient catalysts [93]. These polymer-supported chiral oxaza-borolidinone ligands were prepared both by chemical modification and by the copolymerization shown in Sch. 5 [94]. The polymer-supported chiral ligands were then reacted with borane to give the oxazaborolidines which were used as catalysts in Diels-Alder reaction of cyclopentadiene with methacrolein. 

However, also in this case enantio-selectivities never exceeded the values obtained with the oxazaborolidine in solution, probably because of diffusional limitations within the polymer support, which enhanced the contribution of the non-selective, direct borane reduction of the ketone. In spite of the rather low imprinting effects obtained in these initial attempts, we feel that this approach still represents a most interesting application of molecularly imprinted polymers in catalysis and deserves further attention in the near future. 

Price, M. D., Sui, J. K., Kurth, M. J., Schore, N. E. Oxazaborolidines as Functional Monomers Ketone Reduction Using Polymer-Supported Corey, Bakshi, and Shibata Catalysts. J. Org. Chem. 2002, 67, 8086-8089. 

One of the most powerful asymmetric catalytic reductions of ketones is borane reduction with oxazaborolidine catalyst [92, 93]. Various types of polymer-supported chiral amino alcohols have been prepared and used for the formation... 

Other polymer-supported oxazaborolidine catalysts (e.g., 71 Fig. 6) have also been used for the ketone reductions [107,108]. 

Homogeneous, Soluble Polymer-Supported Oxazaborolidine Catalysts... 

Application of polymer-supported oxazo-type compounds (mainly, oxazo-lidinone, oxazoline, and oxazaborolidine derivatives) to asymmetric reactions 05CJ01039. 

In order to prepare polymer-supported CBS catalyst, monomeric precursors 59, 60 or 61 or bromides 62 and 63 have been synthesized (Scheme 28). The oxazaborolidine could be formed in situ or not before performing the hydride reduction of ketones. 

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

The use of membrane reactors is favorable not only with respect to an increase in the total turnover number. In certain cases the selectivity can also be increased by applying high concentrations of the soluble catalyst together with making use of the behavior of a continuously operated stirred-tank reactor. Basically, this is also possible with a catalyst coupled to an insoluble support, but here the maximum volumetric activity is limited by the number of active sites per mass unit of the catalyst. This has been shown for the enantioselective reduction of ketones (eq. (2)) such as acetophenone 5 with borane 6 in the presence of polymer-enlarged oxazaborolidines 8 and 9 [65-67]. 

The Diels-Alder reaction was performed with cyclopentadiene and methacroleine (Scheme 56) in presence of 15 mol% of the oxazaborolidine and oxazaborolidinone catalysts derived respectively from supported aminoalcohols and from V-sulfonylamino acid polymers. The oxazaborolidine and oxazaborolidinone catalysts were formed in situ by action of BH3, BH2Br, BHBr2 or BBrs. The diastereoselectivity was excellent in favour of the exo adduct and yields from 65 to 99%. It is noteworthy that higher loading of chiral catalyst site in the polymer, lower exo selectivity and enantioselectivity. The diastereoselection depended not only on the nature of the supported ligand, the crosslinker but also on the borane and the solvent. Results are summarized in Table 6. 

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