Boronic acids, carbonylation amides

Palladium-catalysed carbonylation of halides, with carbon monoxide, can be used to prepare esters, amides and ketones by trapping the intermediate acylpalladium halide with alcohols,amines and organometal-lics, respectively. Boronic acids are probably the best organometallics for the preparation of ketones, but conditions must be adjusted to give the best selectivity between the acylation reaction and simple Suzuki coupling of the boronic acid with the starting halide. ... 

In aqueous carbonylation, water (hydroxide ion) is not necessarily the sole nucleophilic agent at the product-forming step of the catalytic cycle. Reactions in the presence of boronic acids may yield ketones, and amines are stronger nucleophiles to give amides, ° though in both reactions acids are formed as by-products. 

Although unable to metallate selenides, dialkyl amides are sufficiently strong to metallate phenylselenoacetals39,46 51) as well as methyl48,52) and phenyl 46,47,52) selenoorthoesters. They are also able to metallate selenoxides 4 9,11 53 55) and selenones 14). Finally selenoacetals are readily available 4,711,12 S6) from carbonyl compounds and selenols in the presence of a Lewis acid and selenoorthoesters have been prepared from orthoesters, selenols, and boron trifluoride etherate47,48,52). 

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. 

Boron or tin (II) Z-enolates are generated by reaction with the corresponding triflates with a carbonyl compound in the presence of tertiary amines like r-P NEt or. M-ethylpiperidine (except when using dicyclopentylboron triflate [407]). E-Enolates are prepared by using dicyclohexyl- or other cyclic chloroboranes in the presence of Et3N or Me NEt [407, 685, 686, 1246, 1247, 1248], Because enolization does not take place under such conditions with esters or aliphatic tertiary amides, thiophenyl esters RGH COSPh have been used as ester/amide substitutes. Furthermore, Z-boron enolates of ketones can be prepared by conjugate addition of acid derivatives of dialkylboranes to a-enones [687],... 

These trends agree with the frontier orbital analysis. In particular, the delivery of hydride from carbon breaks a relatively unpolarised bond, making the hydride notably soft, as we saw earlier in its capacity to attack pyridinium salts preferentially at the 4-position. The metal hydrogen bond will be more polarised, and metal hydrides should therefore be harder. Similarly, the delivery of hydride from boron will make it softer than when it is delivered from the more electropositive metal, aluminium. It also seems that, among a,(3-unsaturated carbonyl compounds, the susceptibility to conjugate reduction increases in the sequence ketones < esters < acids < amides but there are too few examples to be sure. 

In an important experiment, Mukaiyama and coworkers enolized carbonyl compounds under much milder conditions (low temperatures) with dialkylboryl triflate and a sterically hindered tertiary amine base such as 2,6-lutidine (2,6-dimethylpyridine) or diisopropylethylamine (DPEA).95-97 Less-hindered bases led to formation of a stable borane-amide complex (Lewis acid-Lewis base) and prevented the reaction with the carbonyl compound. Masamune et al,98 and Evans et a/.99100 carried out a study to investigate the reasons for the selective enolate formation. They showed that it depends on the boron ligand, base, solvent and the group attached to the carbonyl moiety. Ketones give (Z)-enolates with often excellent selectivity, whereas r-butyl thiolates give selectively the ( )-enolates (equations 32 and 33).100 101 Evans suggests that reactions with 9-BBN triflate are often under thermodynamic control.15 In equation... 

Almost contemporaneously, B.D. Smith and co-workers reported the use of functionalized isophthalamide receptors for the coordination of anions [13]. Smith appended boronate groups to the peripheral aryl groups in order to form interactions between the Lewis acidic boron and the carbonyl oxygens of the amides therefore pre-organizing the receptor into the syn-syn conformation (preferable for anion coordination) and presumably increasing the acidity of the NH group. Proton COSY and NOE difference experiments indicated that the receptor did indeed adopt the desired syn-syn conformation in DMSO-de. NMR titration experiments in DMSO-de at 295 K showed that re-... 

The carbonyl group of an amide is electron-rich because it receives electron density from the delocalized N lone pair. It therefore complexes well with the empty p orbital of the Lewis acidic borane. Hydride transfer is then possible from anionic boron to electrophilic carbon. The resulting tetrahedral intermediate collapses to an imlnium ion that is reduced again by the borane. 

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