Cycloadditions oxazaborolidines

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

Scheme 10.7 1,3-Dipolar cycloadditions of nitrones with 1,1-diethoxypropene catalysed by oxazaborolidines derived A-tosyl-L-a-amino acids.

Cross-linked polymers bearing IV-sulfonyl amino acids as chiral ligands were converted to polymer bound oxazaborolidine catalysts by treatment with borane or bromoborane. In the cycloaddition of cyclopentadiene with methacrolein, these catalysts afforded the same enantioselectivities as their non-polymeric counterparts238. 

In subsequent work, Corey appUed BLA-type cationic oxazaborolidines to several other reactions, including [3 -i- 2] cycloaddition, cyanosilylation, Michael addition, and P-lactone formation. 

If 2-camphanyloxyacrylonitrile (15 R = C8H 02C00) is taken for cycloaddition, diastereoisomeric cycloadducts can be separated, and the basic system, 7-oxabicyclo-[2.2.1]hept-5-en-2-one 17, can be obtained in optically pure form [36]. Another way of obtaining enantiomeric ketones is based on crystallization of a brucine complex obtained from the corresponding cyanohydrines (see Sec. III). Ketone 17 can be converted [e.g., by cis-hydroxylation (—>18), protection of the diol system, and Baeyer-Villiger oxidation] to lactone 19, the opening of which leads to furanuronic acid 20. A new development in this field is based in cycloaddition between furan and 2-chloro- or 2-bromoacrolein in the presence of 5 mol% chiral oxazaborolidine 21 as catalyst [37],... 

Asymmetric 1,3-dipolar cycloaddition of nitrones to ketene acetals is effectively catalyzed by chiral oxazaborolidines derived from N-tosyl-L-a-amino acids to afford 5,5-dialkoxyisoxa-zolidines with high regio- and stereoselectivity [70] (Eq. 8A.46). Hydrolysis of the N-O bond of the resulting chiral adducts under mild conditions yields the corresponding [1-amino esters quantitatively. 

The reaction of diphenylketene with 1,3,2-diazaboroles 234 in hexane at — 20 °C leads to the formation of 1,3,2-oxazaborolidines 238 in 64-70% yield. The reaction proceeds via the coordination of the ketene oxygen to boron 236 followed by a [2+3] cycloaddition yielding the bicyclic intermediate 237. Fission of B-N bond leads to the product formation as yellow to colorless crystals (Scheme 40) <20000M5791>. 

Apart from the conventional transesterification and acid base reaction protocols mentioned above, oxazaborolidines could also be synthesized by a facile [3+2] cycloaddition of the Ar-oxidc 339 with 5-methyl methylidene borane 338 (Equation 15) <2004ZFA508>. 

The Lewis acid catalysed Diels-Alder cycloaddition of the ketone (4i) with cyclopentadiene allows a complete endo selectivity to be reached. Accordingly, the reaction of (4i) with 1.5 equivalents of cyclopentadiene in the presence of one equivalent of Cl2Ti(OiPr)2 in toluene at 0°C fori2 hrs led exclusively to (5i) which has been isolated in 70 % yield. In the presence of 1.5 equivalents of the oxazaborolidine derived from L-N-... 

Scheeren and co-workers have found that the asymmetric 1,3-dipolar cycloaddition of nitrones with ketene acetals is strongly catalyzed by chiral oxazaborolidines derived from A-tosyl-L-a-amino acids (Eq. 83) [59a]. The 5,5-dialkoxyisoxazolidines are... 

Chiral oxazaborolidine salts are useful catalysts not only for enantioselective reductions (i.e., CBS reduction), but also for promoting enantioselective D-A reactions. The cationic Lewis acids formed by reaction of chiral oxazaborolidines with triflic acid [TfOH] or trifluoromethanesulfonimide [(Tf)2NH] coordinate to dienophiles to direct subsequent cycloadditions in a highly controlled fashion. The D-A reactions using these chiral salts proceed in CH2CI2 under very mild conditions at temperatures as low as -95 °C (Table 9.4). ... 

The critical step in the enantioselective and stereocontrolled total synthesis of eunicenone A by E.J. Corey et al. was the highly efficient chiral Lewis acid catalyzed intermolecular Diels-Alder cycloaddition reaction The diene component was mixed with 5 equivalents of 2-bromoacrolein and 0.5 equivalents of the chiral oxazaborolidine catalyst in CH2CI2 at -78 °C for 48h. The reaction gave 80% of the desired cycloadduct in 97% ee and the endolexo selectivity was 98 2. 

The utility of such cycloadditions has been demonstrated by the elaboration of the cycloadducts to complex natural products [60]. For example, the adduct derived from a cyclopentadiene having a 2-bromoallyl sidechain has been converted to an intermediate employed in a previous (racemic) synthesis of gibberel-lic acid. As illustrated in Scheme 12, an exceptionally efficient synthesis of cassi-ol is realized by the successful execution of a rather difficult endo-selective Diels-Alder reaction using a slightly modified oxazaborolidine (11). The high catalyst loading is balanced by the fact that all the carbons and the quaternary center of the natural product are introduced in a single step. 

A powerful catalyst for [2+2]cycloaddition is created from the bicyclic oxazaborolidine 135 and AlBr3. A hydrindanone frequently used in total synthesis of natural products is readily available from one such adduct in chiral form. ... 

Scheme 6.51. Asymmetric cycloaddition of 2-bromoacrolein and cyclopenta-diene using Corey s indenyl oxazaborolidine catalyst [215,216]...

Dipolar cycloadditions. In the reaction of allylic alcohols with nitrile oxides cocomplexation of the alcohol and diisopropyl tartrate to Zn directs the steric course in the formation of 2-isoxazolines. Bonding of the nitrones that participate in cycloadditions to the boron atom of a chiral oxazaborolidine (4) through their oxygen atoms is important to determine the transition states leading to isoxazolidine products. 

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. 

Scheme 7. Enantioselective 1,3-dipolar cycloaddition of nitrones with ketene acetals catalyzed by oxazaborolidines.

Corey et al. [24] have used this oxazaborolidine as an effective catalyst for an efficient synthesis of cassiol and gibberellic acid. Similar high diastereo- (exo endo = 99 1) and enantioselectivity (96 4) was observed in the cycloaddition reaction of furan with 2-bro-moacrolein using oxazaborolidine as catalyst. 

Chiral oxazaborolidines 20 derived from various amino alcohols have been used as catalysts in asymmetric 1,3-dipolar cycloaddition reaction of nitrones with ketene acetals to give substituted isoxazoles in high yield and stereoselectivity but in moderate enantioselectivity (upto 62% ee). This method has also been used for the synthesis of 0-aminoesters... 

A ligand having C2-symmetry is not a necessity and a variety of catalysts are known that promote highly enantioselective Diels-Alder reactions. For example, the oxazaborolidine 148 is a good catalyst for the cycloaddition of cyclopentadi-ene and 2-bromoacrolein (3.104). The cycloaddition reaction is highly diastereo-and enantioselective in favour of the exo-aldehyde. However, the enantioselectiv-ity is poor with this catalyst when the dienophile lacks a substituent (for example bromine) in the 2-position. A solution to this problem is the use of the protonated oxazaborolidine 149, which promotes highly selective cycloaddition of cyclopen-tadiene with a range of dienophiles, such as ethyl vinyl ketone or ethyl acrylate (3.105). Asymmetric cycloaddition of a,p-unsaturated aldehydes or ketones with various dienes can alternatively be achieved in the presence of a chiral secondary amine as a catalyst. 

The CBS (Corey-Bakshi-Shibata) reagent is a chiral catalyst derived from proline. Also known as Corey s oxazaborolidine, it is used in enantioselective bo-rane reduction of ketones, asymmetric Diels-Alder reactions and [3 + 2] cycloadditions. 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

Also, reaction of ketene with 4-nitrophenyl trichloroacetophenone at —25°C in the presence of a quinidine catalyst gives the corresponding /3-lactone in 95 % yield (89 % e,e). Ketene reacts with aldehydes in the presence of oxazaborolidine catalysts to give the j3-lactones in an enantioselective manner The enantioselective [2+2] cycloaddition of silylketenes 221 with a-ketoesters affords the cycloadducts 222 in 86-99 % yield (high e,es) . 

Fig. 6 AlBrs activated oxazaborolidine catalyst for asymmetric furan Diels-Alder reaction and [2+2] cycloaddition...

Very recently, Corey and coworkers have introduced the very powerful cationic chiral Lewis acids (14) [15] and (15) [16], which are derived from protonation of the parent oxazaborolidines with triflic acid and triflimide, respectively. Because of this protonation, the boron atom becomes even more acidic. The authors have demonstrated that catalyst (14) is able to efficiently promote the cycloadditions of 2-substituted acroleins with a variety of dienes (Equation 5) [15]. 

In 1993, Corey and Loh first reported the application of a catalytic enantioselective cycloaddition to fiiran [53]. In the presence of 10mol% of the oxazaborolidine-derived chiral catalyst 74, 2-bromo- and 2-chloroacrolein smoothly underwent cycloaddition (—78°C, 5h) with fiiran to give the cycloadducts 75a,b in >98% chemical yield (exolendo 99 1) with 96 4 and 95 5 enantioselectivity, respectively. The iV-tosylcarboxylic acid precursor of the chiral catalyst could be efficiently recovered for reuse in each case. Bromo derivative 75a served as a valuable precursor for the preparation of a variety of interesting oxabicycles, such as 76-78, in enantiomerically pure form (Scheme 13.23). 

More recently, Corey reported that the chiral oxazaborolidine-aluminum bromide complex 243 [151] efficiently mediates enantioselective cycloadditions between cyclic silyl enol ethers such as 241 and trifluoroethyl acrylate (242, Equation 20) [150]. The corresponding cycloadduct 244 was formed with excellent yield (99%) and selectivity (99% ee, endojexo = 99 1). As a working model, the transition state assembly 245 was proposed to account for the observed facial selectivity. This features a key hydrogen bond to the a-CH of the acrylate (marked in blue) as a crucial stereochemical control element. 

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