Boronic pinanediol derived

Boronic esters are easily prepared from a diol and the boronic acid with removal of water, either chemically or azeotropically. (See Chapter 2 on the protection of diols.) Sterically hindered boronic esters, such as those of pinacol, can be prepared in the presence of water. Boronic esters of simple unhindered diols are quite sensitive to water and hydrolyze readily. On the other hand, very hindered esters, such as the pinacol and pinanediol derivatives, are exceedingly difficult to hydrolyze and often require rather harsh conditions to achieve cleavage. 

This methodology has been developed by Matteson and coworkers, with particular emphasis on chiral boronic esters derived from pinanediol. Sequential chiral centers can be assembled by an iterative procedure with excellent enantiomeric excess at each step. The two chiral centers in eldanolide (37), for example, were assembled in this manner (Scheme 36). ... 

Novel tetrahedral boronate complexes have been prepared as potential ligands for affinity chromatography either from the amination (LiN(TMS)2) of a-haloalkylboronates followed by A-acetyl-ation (i.e., (132)) or, alternatively, from the a-iodo derivatives and acetamidine (i.e., (133)) (Scheme 17). The 1,3,2-dioxaborinanes proved to be less stable than the pinanediol derivatives to silica gel. "B NMR as well as other data confirmed their chelated nature (e.g., (132) d 6.8) <92JOM(43i)255>. Spiroborates (e.g. (134)) have also been prepared from boric acid, diols, and enolizable 1,3-dicarbonyl compounds <86JPR755>. Vinylzirconocenes (135) are converted to vinylboronates (136) with chloroboranes <910M3777>. The hydrozirconation of 5-vinylboronates (137) produces the mixed... 

The two contiguous stereocenters present in the aldehyde 155 were installed in a straightforward manner and with an extremely high stereoselectivity using the dihalomethyllithium insertion method of Matteson (Scheme 3) [157]. The (-i-)-pinanediol boronic ester derivative... 

Several additional [o-(bistrimethylsilylamino)alkyl]boronic and derived (a-ac-etamidoalkyl)boronic esters were synthesized in early work [64, 65]. Pinanediol (R)-(bis-l-trimethylsilylamino-3-methylbutyl)boronate (123) has subsequently proved to be the most important synthetic intermediate to date of diis series for pharmaceutical purposes. Acetamido compounds synthesized are summarized in structure 124 (Figure 8.2). 

S)-Pinanediol boronic esters 2 with (dichloromethyl)lithium produce (aS)-a-chloro boronic esters 3. The first experiments provided diastereomerie ratios in the range 75 25 to 98 2. The best results (>94 6) were obtained with phenyl, ethenyl, or 1-phenylethyl attached to the boron atom39 40. The diastereomerie ratios were estimated from the rotations of esters of derived secondary alcohols. It was subsequently found that zinc chloride catalysis of the rearrangement of the intermediate borate complexes 2 improved the yields, usually to 85-95%, with diastereo-meric ratios often >99 1 when R1 = alkyl, as shown by NMR measurements15,43. 

A)-Pinanediol ethylboronate with (l,l-dichloroelhyl)lithium yields the (S)-a-chloro boronic ester (89 11 d.r.), which is converted by phenylmagnesium bromide to the (S)-tert-alkylboronate, the same isomer obtained from (S )-pinanediol phenylboronate. The enantiomeric excess of the derived (R)-2-phenyl-2-butanol is 70%. 

In a subsequent investigation by the author with others (2) (+)-pinanediol 4-bromo-(R)-aminobutane boronate hydrochloride and other cr-bromo boronic esters have been used as intermediates in the preparation of peptide derivatives (2). 

By a similar method, the (Z)-crotylborate is synthesized from cA-2-butene in 70-75% yield with a 98% isomeric purity. The tartrate esters of allylboronic acids are an excellent reagent for asymmetric allylboration of carbonyl compounds. Allyl(diisopinocampheyl)borane [51] and the allylic boron derivatives of ester and amide, such as camphordiol [52], pinanediol [53], 1,2-diphenyl-1,2-ethylenediamine [54], have also been successfully used for asymmetric allylboration of carbonyls. 

There are several situations where cleavage of a 1,3,2-dioxaborolane to the boronic acid and diol is useful. One of these is for removal of a chiral director and replacement by its enantiomer. The first time we encountered this problem, a pinanediol ester was converted to the boronic acid via destructive cleavage of the pinanediol with boron trichloride (14). More recently, it has proved possible to convert an (R)-DICHED a-benzyloxy boronate (20) to the free bororric acid (23) with the aid of sodium hydroxide and a tris(hydroxymethyl)methane to form water soluble derivative 21 (R = CH2OH or NH(CHi)3S03 ) plus water insoluble (R)-DICHED (22). Treatment of 23 with (S)-DICHED (24) then yielded diastereomer 25 (76%, 97-98% diastereomeric purity). Further chain extension and alkylation led to 26 and 27, and deboronation yielded 28, all of which are stereoisomers that could not be accessed directly with a single chiral director (Scheme 6). 

The use of chiral boronic esters in the Petasis borono-Mannich reaction has been reported to result in low levels of enantioselectivity of the adducts at room temperature (6-15% ee) [48]. Auxiliaries used in this study by Scobie and co-workers included pinanediol and tartaric acid derived alkenylboronates. Morpholine was the only secondary amine used, with the primary amine ethyl glycinate failing to react. 

A limitation of pinanediol boronic esters (15) results from the difference between the two diastereotopic faces of the trigonal boron atom. The sequential double di-astereodifferentiation observed with chiral directors having C2-symmetry is not possible. Borate anion 16 derived from 15 rearranges to (a-chloroalkyl)boronic esters 17 and 18 in a ratio that usually exceeds 50 1 (Scheme 8.3) [12]. Alkylmetallic reagents attack 17 from the less hindered side to form 19, in which the chloride to be displaced is not in a comparable steric environment to that in 16 (28). The major diastereomer 20 is produced in about the same proportion as its precursor 17 (Scheme 8.3). 

Following the general procedure used for the preparation of 48, a considerable variety of (alkoxyalkyl)boronic esters have been prepared. Scheme 8.12 illustrates the synthesis of L-ribose [38). Benzyl oxide substitution on pinanediol (chloromethyl)-boronate (49) yielded the benzyloxy derivative 50. Benzyl oxide substitution in the conversion of 50 into 51 worked best with the bromo intermediate derived from (di-... 

Different studies were carried out to develop diastereocontrolled versions of these Diels-Alder reactions. Better results were obtained when an optically pure diol was used as chiral director. The tandem reaction involving a 1,3-dienylboronate derived from tartrate esters proceeded with 70% enantiomeric excess (Scheme 9.35) [76]. The hetero-Diels-Alder reaction of enantiomerically pure (-t)-pinanediol 1,3-dienyl-boronate with an azo dienophile gave the J -configured endo cycloadduct as the single stereoisomer [77]. 

Chain extension using an insertion reaction of dichloromethyl-lithium or dibromomethyllithium with a cyclic chiral boronate derivative, (S)-pinanediol[(benzyloxy)methylJboronate (2), has been used in a synthesis of L-ribose in 13% overall yield (Scheme 3)- A new... 

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