Boron-containing reagents

The synthetic method used to accomplish this is an indirect one known as hydroboration-oxidation. It was developed by Professor Herbert C. Brown and his coworkers at Purdue University in the 1950s as part of a broad progran designed to apply boron-containing reagents to organic chemical synthesis. The number of applications is so large (hydroboration-oxidation is just one of them) and the work so novel that Brown was a corecipient of the 1979 Nobel Prize in chemistry. 

Two methods, both involving boron-containing reagents, have been devised for the regioselective ortho hydroxymethylation of phenols or aromatic amines. 

The challenge to chemists has been to develop boron-containing reagents that can be selectively concentrated in cancerous tissue while avoiding healthy tissue. Various approaches to this task have been attempted. ... 

Hydroboration-oxidation was deveioped by Professor Herbert C. Brown [Nobei Prize in Chemistry (1979)] as part of a broad program designed to appiy boron-containing reagents to organic chemicai synthesis. 

Boron nitride may be obtained in three primary crystalline modifications (2) a, j3, and y. The most commonly encountered a form has a graphitic structure (hexagonal cell, a = 2.504 A, c = 6.661 A). For many years, this modification has been prepared from combinations of cheap boron and nitrogen containing reagents, e.g. B(0H)3 and (NH2)C0, B(0H)3, C and N2 or KBH4 and NH4C1 (3-5). More... 

In particular, 1,3-dithiane prepared from dimethoxymethane (methylal) and pro pane-1,3-dithiol in the presence of boron trifluoride-etherate,237 and 2-alkyl-1,3-dithianes prepared similarly from aldehydes,2383 are important acyl anion equivalents. These and other uses are discussed in Sections 5.7.5, p. 596, and 6.6.1, p. 909. A wide-ranging review of the reversal of polarity of the carbonyl group through the formation of these sulphur-containing reagents has emphasised their value in organic synthesis.2388... 

Macrocycles. This reagent was used twice in an assembly of aplasomycin (5), a boron-containing macrolide with antibiotic properties. It was used to effect alcrification of 1 with 2 in 98% yield and again for cyclization of 3 to the macrocycle 4 ill 71% yield under conditions of only moderate dilution. After minor adjustments ol the functional groups, the metal was introduced by reaction with trimethylborate hi give 5. 

An especially efficient reagent of this type is the boron-containing five-membered ring compound shown in Figure 3.30. Since this reagent is quite difficult to synthesize, it has not been used much in asymmetric synthesis. Nonetheless, this reagent will be presented here simply because it is particularly easy to see with which face of aC=C double bond it will react. 

The first step is a reaction you haven t yet met—it comes in Chapter 47. All you need to know now is that the reagent, a boron-containing compound called 9-borabicyclononane (9-BBN), hydrates one of the double bonds in the reverse fashion to what you would expect with acid or Hg2+ (Chapter 20) and stereo specifically (H and OH go in cis). The resulting alcohol is mesylaled (p. 486) in the usual way. This puts in H and OMs stereo specifically cis to each other. 

Another useful reagent for macrolactonization via mixed phosphoric anhydride is N,N- bis(2-oxo-3-oxazolidinyl)phosphordiamidic chloride (BOP-Cl, 64), which was used by Corey and coworkers [41] in the first synthesis of aplasmomycin (67), a novel boron-containing macrocyclic antibiotic. As shown in Scheme 21, the linear precursor 65 was treated with 3 equiv of BOP-Cl (64) and 7 equiv of triethylamine in dichloromethane at 23 °C for 6 h to give the dilactone 66 in 71% yield. 

Such a mechanism was unlikely as addition of an external trap, 1,1-diphenylethylene, had no effect on the course of the arylation of p-ketoesters.i l A second approach involved the use of an internal trapping system which had been successfully used in the study of the radical reactions of arenediazonium salts.The internal trap containing reagent, ( rf/io-allyloxyphenyl)lead triacetate (94), can be easily prepared from the corresponding boronic acid. 2 Reaction with various types of nucleophiles, such as ethyl 2-oxocyclopentanecarboxylate (86), mesitol (36), the sodium salt of nitropropane, iodide and azide always afforded the C-arylation products in high yield. No trace of the 3-substituted dihydrobenzofurans, expected in a mechanism involving the intermediacy of free radicals, could be detected. 

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