Oxazaborolidine proline derived

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. 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

Hydroboration of simple ketones eatalyzed by proline-derived oxazaborolidine 45 provides a practical method for the preparation of chiral secondary alcohols (Scheme 13). Under this protocol, a key intermediate in the synthesis of MK-0417 (44), a water-soluble carbonic anhydrase inhibitor, has been prepared... 

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],... 

There are reports that extend the nature of the catalyst beyond an oxazaborolidine framework. One such example made use of a chiral guanidine catalyst.11 Proline-derived 25 was converted to guanidine 26 in good yield. This species was capable of reducing ketones 27 to alcohols 28 by the addition of BH3-SMe2. 

Proline-derived oxazaborolidines 45 have shown to be effective pre-catalysts with triflic acid as an activator to generate cationic Lewis acids.18,15 The optimal proportions of 45 and triflic acid was found to be 1.2 1. Protonation of 45 produced a 1.5 1 mixture of 46 and 47 as determined by low temperature H NMR. Their interconversion at low temperature (-80 °C) is slow on the NMR timescale. However, this interconversion increases as the temperature rises and at 0 °C this becomes rapid (Tc). Phenyl or o-tolyl were determined to be the best substituents for the R group in 45. For the Ar group of 45, phenyl and 3,5-dimethylphenyl were determined to be optimal. 

In 1987, Corey, Bakshi and Shibata demonstrated that the enantioselective reduction of ketones could be catalysed by oxazaborolidines. They showed that acetophenone was reduced only slowly by BHs-THF alone, and that oxazaborohdine (3.114) alone did not cause reduction. However, in combination they reduced acetophenone in one minute at room temperature. Using just 2.5 mol% of oxazaborolidine, and stoichiometric BHs-THF still provided excellent enantios-electivity. In the same initial commimication, proline-derived oxazaborolidine (3.115) was identified as a catalyst that was suitable for the reduction of a range of ketones, including acetophenone (3.32) and ketones (3.116) and (3.117). 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

The oxazaborolidines B and C derived from proline are also effective catalysts. The protonated forms of these catalysts, generated using triflic acid or triflimide, are very active catalysts,95 and the triflimide version is more stable above 0° C. Another protonated catalyst D is derived from 2-cyclopentenylacetic acid. 

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. 

The enantioselectivities reported for the reduction of acetophenone and 1-tetralone using several representative chiral (4S)-oxazaborolidine catalysts are summarized in Table 1. The oxaz-aborolidines derived from (S)-azetidinecarboxylic acid and (S)-proline provide the best results. It is interesting to note tbe reversal in enantioselectivity going from catalyst (5a) to (6a). 

Bicyclic 1,3,2-oxazaborolidines synthesized from proline are the original chem-/>mes. The crystalline BH3 adduct of the 1-methyl derivative can be prepared from... 

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. 

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. 

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