Reaction with boronic esters

Boronic acids bearing strong electron-poor aromatic groups (such as pyridinyl) were reported to lack reactivity in the Petasis-Akritopoulou reaction, using standard conditions (dichloromethane, room temperature) [54]. Boronic esters were also studied [57] and the authors reported that the mechanism of formation of the boronate species was different from that with phenylboronic acid derivatives. Piettre and coworkers considered the use of hexafluoro-iso-propyl alcohol (HFIP), which is an alcohol with higher ionizing power, as the solvent in the Petasis-Akritopoulou reaction with boronic esters (Scheme 6.43). Compared to the use of methanol as solvent and microwave-assisted irradiation (MW), the yields were much higher (a maximum of 99% yield was obtained ) [58]. 

Aldehydes aie conveniendy synthetized by the reaction of boronic esters with dichloromethylhthium or (phenylthio)methoxymethylhthium (336,337). The synthesis of medium-ting boracyclane stmctures by stepwise ring enlargement is based on the reaction of B-methoxyboracycles with chloromethylhthium (338). 

These coupling reactions can also be done with boronate esters activated by conversion to ate reagents by reaction with alkyllithium compounds.279 For example, analogs of leukotrienes have been synthesized in this way. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

It has been demonstrated that optically active oxetanes can be formed from oxazolidinone 92, a crotonic acid moiety functionalized with Evans chiral auxiliary (Scheme 18) <1997JOC5048>. In this two-step aldol-cyclization sequence, the use of 92 in a deconjugative aldol reaction, with boron enolates and ethanal, led to formation of the syn-aldol 93. This product was then converted to the corresponding oxetanes, 94a and 94b, via a cyclization with iodine and sodium hydrogencarbonate. This reaction sequence was explored with other aldehydes to yield optically active oxetanes in similar yields. Unlike previous experiments using the methyl ester of crotonic acid, in an analogous reaction sequence rather than the oxazolidinone, there was no competing THF formation. 

Reaction of boronic esters, RB(OR )2, with dichloromethyllithium, LiCHCl2, inserts the CHC1 unit into the carbon-boron bond of the boronic ester. This is known as boronic ester homologation. If boronic esters derived from homochiral alcohols are used in this reaction, then new homochiral centres may be generated as will be illustrated below. 

Fatty acid analysis of a fat is nowadays a relatively routine analytical operation. After methylation of the fat using reaction with boron trifluoride/methanol, boron trichloride/methanol, methanolic hydrogen chloride solution, diazomethane or, if free fatty acids are not present, alkaline catalysts such as sodium methoxide/methanol, the prepared methyl esters are then analysed by GC on a polar column such as CpSil 88, BPX70 or SP2340. The high polarity of the column is necessary to separate the saturated and unsaturated fatty acids fully. The fatty acid composition of a milk fat sample is thus relatively easily obtained, and was therefore one of the first techniques investigated for authentication purposes. 

Table 17 indicates some limitations of the amine hydrofluorides in the reaction with glycidic esters. In the least-substituted case (entry 1) the yield is low. On the other hand, the fully substituted glycidic esters (entries 8 and 9) do not react at all with the amine hydrofluoride, probably due to steric hindrance. This type of epoxide gives better results with other fluorination reagents, e.g. they can be opened to the fluorohydrins in good yield with hydrogen fluoride in the presence of the boron trifluoride-diethyl ether complex (sec Section 1.1.4.3.2.1.2.).37... 

Tin-lithium exchanges. A method for the preparation of a-hydroxy boronic esters takes advantage of the facile Sn/Li exchange of a-stannylalkyl MOM ethers. Subsequent reaction of the lithioalkyl ethers with boronic esters displaces one of the alkoxy groups of the latter." The reaction of chiral A-tributylstannylmethyl-2-methoxymethylpyrrolidine with BuLi and then aldehydes gives diastereomeric mixtures of P-amino alcohols. ... 

Addition compounds of alkali-metal hydrides. 25. Rapid reaction of boronic-esters and acids with lithium aluminium hydride. A novel and quantitative synthesis of lithium monoorganylborohydrides, B.Singaram, T.E.Cole and H.C.Brown, Organometalllcs, 1984, 3, 774. 

In earlier work, we had shown that a-azido boronic esters are surprisingly stable and will undergo the reaction with (dichloromethyl)lithium, albeit with some complications caused by azide reactivity (1). We have also used azido boronic esters as intermediates in an asymmetric amino acid synthesis (21). It now appears that azido boronic esters may be the best general protected amine functionality for synthetic purposes, and we will report new flndings in this area shortly (22). Older findings with azido boronic esters as well as the compatibility or incompatibility of other polar functionality with boronic ester chemistry have been reviewed elsewhere recently in considerable detail (23). 

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