Boronic DICHED derivatives

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). 

Cyclobutane synthesis allows introduction of substituents on the cyclobutane ring in various patterns (Scheme 8.24) [55], Allyl bromide with boron trichloride and tri-ethylsilane yields the alkyldichloroborane 103, which is converted into pinacol (3-bro-mopropyl)boronate (104) and on to the cyano derivative 105 by standard methods. Transesterification of 105 and reaction with LiCHClj was used to make 100. However, 105 can be deprotonated and monoalkylated efficiently, and transesterification then yields 106. Transesterification with DICHED and asymmetric insertion of the CHCl group furnishes 107, which cyclizes to 108 or 109 with about the same 20 1 di-astereoselection as seen with the unsubstituted intermediate 100. The pattern of substitution shown by 111 was achieved via reaction of pinacol (bromomethyl)boronate (63) with lithioacetonitrile to form 110, which underwent chain extension and substitution in the usual manner. It was necessary to construct 110 in this way because substitution of a (p-haloalkyl)boronic acid is not possible. With R = H or CH3, substituents included Me, Bu, and OBn [55]. 

The first application of the alkyltrifluoroborate salts was the conversion into alkyldihaloboranes by silyl hahdes and subsequent reaction with alkyl azides [77]. An example of a usefid synthesis was the preparation of (S)-2-phenylpyrrolidine (141) (Scheme 8.32). (S)-DICHED (3-bromopropyl)boronate (13S) was converted into the 3-azido derivative 136 at reflux temperature under phase-transfer conditions. The usual reaction with (dichloromethyl)lithium followed by phenylmagnesium bromide to form DICHED ester 137 was followed by treatment with potassium bifluoride in aqueous methanol to provide the alkyltrifluoroborate salt 138. Neither boronic esters nor alkyltrifluoroborate salts react with alkyl azides. Reaction of 138 with trimethylsi-lyl chloride yielded (S)-2-phenylpyrrolidine (141), but reaction with silicon tetrachloride proved much faster and more efficient. At first it was thought that the intermediates 139 and 140 were probably difluoroboranes in accord with literature precedent [76], but careftil reinvestigation has revealed that reaction of alkyltrifluoroborate salts with silicon tetrachloride in coordinating solvents yields alkyldichloroboranes [78]. 

A -Alkylanilino)dich]oroboranes (5), prepared in situ from iV-alkylanilines and boron trichloride, are versatile intermediates for the synthesis of ort/w-fimctionalized aniline derivatives (eqs 3-5). The regioselective ortho hydroxyalkylation can be achieved with aromatic aldehydes. ... 

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