Azaborolidines

Itsuno et al.68c found that among the imines 150-153, TV-trimethylsilylimine derivative 153a has the highest reactivity. When it is treated with /i-allylox-azaborolidine 156, a compound derived from toluenesulfonyl norephedrine 155, a product with high selectivity (92% ee) is obtained. Scheme 3-53 depicts the... 

In summary, many attempts have been made at achieving enantioselective reduction of ketones. Modified lithium aluminum hydride as well as the ox-azaborolidine approach have proved to be very successful. Asymmetric hydrogenation catalyzed by a chiral ligand-coordinated transition metal complex also gives good results. Figure 6-7 lists some of the most useful chiral compounds relevant to the enantioselective reduction of prochiral ketones, and interested readers may find the corresponding applications in a number of review articles.77,96,97... 

The alternative use of LiH/BFjOEtj as a reducing agent for the in situ generation of borane is used to save costs [42], Polymer-enlarged ox-azaborolidines have been applied with success in a membrane reactor [43],... 

Application as a Component of an Asymmetric Catalyst. Amino alcohol (1) has proven to be a highly versatile ligand for use in asymmetric catalysts for a series of reactions. One of the most comprehensively studied uses is as an ox-azaborolidine derivative such as 8 for the asymmetric control of the reduction of ketones by borane. Although its use was first described with stoichiometric levels of 1 being employed for the reduction of both ketones and oximes, development of the system has delivered a catalytic method requiring only 5-10 mol % catalyst. Enantiomeric excesses of over 85% and as high as 96% have been achieved for a range... 

Problems with the preparation and stability of oxazaborolidine (6) led to the development of a series of B-substituted ox-azaborolidines derived from diphenylprolinol. The B-methyl substituted oxazaborolidine (9a) was first prepared (eq 5) by reaction of diphenylprolinol (1) with methylboronic acid under dehydrating conditions (toluene at 23 °C in the presence of 4 X molecular sieves or toluene at reflux using a Dean-Stark trap) followed by vacuum distillation (0.1 mmHg, 170°C). Based on NMR evidence, the product (mp 74-87 °C) was reported to be a mixture of monomer and dimer. The corresponding B-butyloxazaborolidine (9c), prepared in a similar manner from n-butylboronic acid, was also reported to be a mixture of monomer and dimer. Subsequent investigations demonstrated that the reported dimers were in fact the intermediate (8) and the more stable disproportionation product (10) (eq 6). Furthermore, the presence of (8) or (10) was demonstrated to be deleterious to the enantioselectivity of the catalyst. ... 

The tert-butyl ethers of serine and threonine are available by tert-butylation of various starting materials, e.g. Z-Ser-OMe/Z-Thr-OMe,P l Z-Ser-ONbz/Z-Thr-ONbz,P l and H-Ser-OMe TosOH/H-Thr-OMe -TosOHt l (see also Table 3). Analogous to benzyl ether formation, the tert-butyl ethers can also be produced via 4-substituted 2,2-difluoro-l,3,2-ox-azaborolidin-5-ones.t In most cases, isobutylene with 4-toluenesulfonic add, or a concentrated inorganic acid is used as catalyst for tert-butylation. The use of Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH in solid-phase peptide synthesis is very well established. These annino acid derivatives can be synthesized either by introduction of the Fmoc group into H-Ser(tBu)-OH and H-Thr(tBu)-OH or by tert-butylation of the Fmoc-protected serine and threonine (Table 3). ... 

Saturated 1,2-diborolanes 1 are covered although carboranes and heterofullerenes, which might fall in this class, have been omitted. The first example of a 1,2-silaboracyclopentane 2 has appeared. The saturated boron-nitrogen heterocyle 1,2-azaborolidine 3 is represented in the literature as are the unsaturated 2,5-dihydro-17/-l,2-azaboroles 4,... 

Diboroles have been routinely analyzed by electron impact mass spectrometry. The method has been used to confirm only molecular masses when 2,3-dihydro-l,3-thiaboroles <19980M2379, 19990M1821> and 2-(2,2-dimethyl-propylidene)-4,5-diethyl-l,3-diiodo-2,3-dihydro-177-l,3-diborole 22 <2002ZN1125> were measured. When the molecular masses of other 2,3-dihydro-l/7-l,3-diboroles, 1,3-azaborolidines, 2,3-dihydro-l//-l, 3-stannaboroles, and... 

Thermodynamic aspects of 1,3-diborolanes, 2,3-dihydro-l//-l,3-diboroles, 1,3-azaborolidines, 2,3-dihydro-l,3-thia-boroles 2,3-dihydro-l//-l,3-stannaboroles, or 2,3-dihydro-l//-l,3-silaboroles are only sparsely mentioned. It has been found that the 127t-electron antiaromatic heterocycle 23 is stabilized by electron delocalization via the boron atom (cf. compound 9) <2002ZN1125>. Noteworthy is the comparison between the 8jt-electron antiaromatic 2,3-dihydro-l,3-benzothiaborole 24 or 4jt-electron antiaromatic 2,3-dihydro-l,3-thiaborole 26 and the corresponding lOtt-electron 25 or 67t-electron 27 aromatic lithium compounds, the latter forming stable Jt-coordinated transition metal complexes. 

The only compound so far known containing a 1,3-azaborolidine ring is 9-mesityl-97/-pyrrolo[l,2- ][l,3]benzaza-borole 23 <1999JCM264>. This compound was synthesized by treatment of l-(2-bromophenyl)-l/7-pyrrole 54 with -butyllithium in ether to give 2,2 -dilithio-l-phenylpyrrole 55, which was subsequently reacted with dimethoxy-mesitylborane to afford 23 in 76% yield (Scheme 7). 

Five-membered heterocycles with two adjacent heteroatoms with at least one boron atom were discussed very sparsely in the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) <84CHEC-l(l)637>. Only the class of 1,2-azaborolines was described a little more comprehensively. Other types such as 1,2-azaborolidines, the 1,2-oxaborolanes, and the 1,2-oxaboroles were completely neglected. For that reason it seems appropriate to discuss these heterocycles in more detail. This requires partial consideration of literature before 1982. 

Starting with borylated allylamines, ring formation can be reached by thermolysis with B—C linkage. Thus, the thermolysis of allyl-r-butylaminobutylphenylborane at 200-210°C with loss of butene is a route to 1,2-azaborolidines (Equation (16)) <80AG(E)54>. 

As 4-atom fragments, allylamines are often used for the synthesis of 1,2-azaborolidines, 1,2-azoniaboratolidines, 1,2-azaboroles, and 1,2-azoniaboratoles. 1,2-Azaborolidines are generally formed if borane-amine adducts are thermally burdened in the presence of alkyl-, allyl-, and diallyl amines. These reactions can also be described as hydroborations of diallyl compounds (Equations (22) and (23)) <70ZOB1528,76IOC2803>. 

The l-azonia-5-borata-derivatives with ip -hybridized nitrogen and boron atoms have been found to be generated together with 1,2-azaborolidines (see Section 3.17.9.2). 

A very special route to a 1,2-azaborolidine was described by Noth and co-workers (Equation (36)) <93CB1551>. 

A very common route to 1,2-azoniaboratolidines uses the quaternization of boron and nitrogen in 1,2-azaborolidines. The most simple reaction is that with water (Equation (37)) <65MI 317-01>. 

The structurally more rigid (S)-prolinol-based amino alcohol was introduced early in the study of borane reductions [18]. Sterically more hindered ox-azaborolidines 4 (Fig. 1) based on (S)-(-)-diphenylhydroxymethylpyrrolidine have been prepared by Corey [23,25]. These catalysts have been widely used for the borane reduction of various kinds of ketones. After these successful results had appeared for asymmetric ketone reduction, several oxazaborohdines (Fig. 1) were prepared. Many of them were successfully used in the reduction of aromatic ketones. Selected results of enantioselective borane reduction using various oxazaborohdines are shown in Scheme 4. The table to this scheme shows only the data obtained from the reduction of acetophenone as a representative aromatic ketone. In most cases, high enantioselectivity is obtained in the nearly quantitative yield. 

Hydroboration of the C-C unsaturated bond may be a possible side reaction in the reduction of a,P-unsatuxated ketones. However, in many cases, some ox-azaborolidines successfully catalyze the selective reduction of ketone carbonyls (Scheme 6). The borane reduction of 2-methylnon-l-en-3-one with oxazaborolidine 45 showed a clean conversion to the allylic alcohol (98%, 92% ee S) [82]. The same catalyst [83] and 4b [84] were effective for the reduction of a,P-ynones [83]. 

H-Catecholborane was used as a reductant for aldehydes in the presence of ox-azaborolidine catalyst 66 (Fig. 5). 

Figure1.15 Examples of azaborolidines and other heterocyclic analogues.

---