Oxazaborolidine derivatives

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

A valine-derived oxazaborolidine derivative has been found to be subject to activation by Lewis acids, with SnCl4 being particularly effective.98 This catalyst combination also has reduced sensitivity to water and other Lewis bases. 

Cationic oxazaborolidines derived from a,a-diphenylpyrrolidine-2-methanol have been examined and shown to considerably extend the range of dienophiles that are responsive to the catalysts." The best proton source for activation of these catalysts is triflimide, (CF3S02)2NH.100 For example, cyclohexenone and cyclopentadiene react with 93% enantioselectivity using catalyst J. 

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. 

BH3.Me2S reduction of aryl alkyl ketones can be carried out with ees up to 98% using 3 mol% of a chiral oxazaborolidine derived from (-)-/l-pinenc.3 5... 

In particular, reduction of unsymmetric ketones to alcohols has become one of the more useful reactions. To achieve the selective preparation of one enantiomer of the alcohol, chemists first modified the classical reagents with optically active ligands this led to modified hydrides. The second method consisted of reaction of the ketone with a classical reducing agent in the presence of a chiral catalyst. The aim of this chapter is to highlight one of the best practical methods that could be used on an industrial scale the oxazaborolidine catalyzed reduction.1 1 This chapter gives an introductory overview of oxazaborolidine reductions and covers those of proline derivatives in-depth. For the oxazaborolidine derivatives of l-amino-2-indanol for ketone reductions see Chapter 17. 

Researchers at Sepracor later disclosed the use of a new class of chiral oxazaborolidines derived from r/. v-aminoindanol in the enantioselective borane reduction of a-haloketones.6,7 The 5-hydrogen oxazaborolidine ligand 10 was prepared in situ from d,v-aminoindanol 1 and BH3 THF.8 Stock solutions of 5-methyl oxazaborolidine 11-16 were obtained by reaction of the corresponding N-alkyl aminoindanol with trimethyl boroxine.6,7 5-Methyl catalyst 11 was found to be more selective (94% ee at 0°C) than the 5-hydrogen catalyst 10 (89% ee at 0°C), and enantioselectivities with 11 increased at lower temperatures (96% ee at -20°C). The catalyst structure was modified by introduction of A-a I kyI substituents. As a general trend, reactivities and selectivities decreased as the steric bulk or the chelating ability of the A -alkyl substituent increased (Scheme 17.4). 

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-... 

In addition to these simple examples, oxazaborolidines derived from dipheny Iprolinol have been used as enantioselective catalysts for the preparation of prostaglandins, PAF antagonists, a key intermediate of ginkgolide B, a key intermediate of forskolin, ... 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

Oxazaborolidines derived from proline (3) (see a,a-Diphenyl-2-pyrrolidinemetha not) and valine (1 R = i-Pr) (see 2-Amino-3-methyl-1,1-diphenyl-1-butanol) have received the most attention. 

Enantioselective Addition of Diethylzinc to Aldehydes. Oxazaborolidines derived from ephedrine have been used to catalyze the addition of Diethylzinc to aldehydes (eq 13). Both... 

Other Applications. Chiral oxazaborolidines derived from ephedrine have also been used in asymmetric hydroborations, and as reagents to determine the enantiomeric purity of secondary alcohols. Chiral l,3,2-oxazaborolidin-5-ones derived from amino acids have been used as asymmetric catalysts for the Diels-Alder reaction,and the aldol reaction. ... 

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... 

A disulfide-linked bis(aminoethanol) 82 prepared from L-cystine also catalyzes the borane reduction of ketones. Other oxazaborolidine derivatives are obtained from 83, 84, " and 85, " and polymer-bound species. Those derived from the ephedra bases find use in the asymmetric reduction of imines. bicyclic oxazaborolidine generated... 

Additional catalysts have also been proposed for the reaction of Et2Zn with aromatic aldehydes, including (proline derivative 2.13 (R = CPh2OH) [110] and a four-membered analog [646], (1S,2R)-1.61 (R = S02Tol), 2.47, and pyridine-derived aminoalcohols [110, 644, 651, 1173]. Other catalysts include sulfur derivatives of ephedra alkaloids [645, 728], the Li diamide of piperazine 2.46, diamines 1.64 (R = 2-Py) and other related 2-aminopyridines [367, 648, 649, 1174], p-Hydroxysulfoximines have also been used as catalysts in these reactions [1175], as has an oxazaborolidine derived from ephedrine [1176],... 

A major advance in the evolution of chiral boron reagents was reported initially by Itsuno and co-workers in 1981.5 Stereoselectivities up to 73% ee were observed using the 1,3,2-oxazaborolidine derived from p-amino alcohols. Thus (S)-valinol 5 in reaction with borane afforded 6. 

A tetracyclic oxazaborolidine derived from tryptophol can be used to reduce ketones enantioselectively. It is not effective for imines. 

Later, several oxazaborolidines derived from various amino alcohols have been used for the reduction of ketones [6] and ketoimines. 

The reaction of borane methyl sulfide with 2-amino-2-methylpropan-l-ol has been studied. Instead of the expected five-membered oxazaborolidine derivatives, two polycyclic structures with NBN and OBN moieties were obtained, and their structures were determined by X-ray crystallography <2006JOM1993>. 

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

Asymmetric reduction of ketimines to sec-aminesf Of the various hydride reagents found to achieve high enantioselective reduction of ketones, the oxazaborolidine 1 of Itsuno, prepared from BH3 and (S)-(—)-2-amino-3-methyl-I,l-diphenylbutane-l-ol, derived from (S)-valine, (12,31), is the most effective in terms of asymmetric induction. Like Corey s oxazaborolidines derived from (S)-proline, 1 can also be used in catalytic amounts. The highest enantioselectivities obtain in reduction of N-phenylimines of aromatic ketones (as high as 88% ee). The enantioselectivities are lower in the case of N-t-butylimines of aryl ketones (80% ee). Reduction of N-phenylimines of prochiral dialkyl ketones with 1 results in 10-25% ees. 

Futatsugi K, Yamamoto H (2005) Oxazaborolidine-derived Lewis acid assisted Lewis acid as a moisture-tolerant catalyst for enantioselective Diels-Alder reactions. Angew Chem Int Ed Engl 44 1484-1487... 

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). 

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