Azides reaction with organoboranes

Synthesis of Primary Amines via the Reaction of Organoboranes with Trimethyl silyl Azide in Neutral Medium 2-exo-Norbornyl Amine. 

The reaction of trialkylboranes with iV-chloroalkylamines can be used to synthesize a wide variety of functionally substituted dialkylamines in good yields [66,67], and it complements the synthesis of secondary amines via the reaction of trialkylboranes with organic azides. The reaction is analogous to the reaction of chloramine with organoboranes, and presumably occurs via an anionotropic migration of an alkyl group from boron to nitrogen (Scheme 24). 

Organoboranes can be used for the synthesis of various organic compounds containing an amino group . The most common procedures involve the reaction of organoboranes with azides, with hydroxylamine derivatives, or with chloroamines. All amination reactions proceed via intermediate formation of a borate complex followed by anionotropic rearrangement to form the new C—N bond (Equation (21)). 

A more convenient procedure for the synthesis of (113) from (5) was later elaborated <9UOM(4l2)l>. It is based on the intramolecular version of the reaction of organoboranes with organic azides. The THF complex of 1-boraadamantane (5a) is treated with iodine in the presence of an excess of sodium azide. The iodine atom in the intermediately formed borabicycle (118) undergoes an easy nucleophilic substitution by azide ions. The subsequent anionotropic rearrangement in the borabicyclic azide (119) leads (after the oxidation of the reaction mixture) to aminoalcohol (120), which is smoothly converted to 1-azaadamantane (113). The yield of (113) in this synthesis is 40-45% based on (5a), or 20-22% based on triallylborane (Scheme 44). 

Organoboranes react with a mixture of aqueous NH3 and NaOCl to produce primary amines. It is likely that the actual reagent is chloramine NH2CI. Chloramine itself,hydroxylamine-O-sulfonic acid in diglyme, and trimethyl-silyl azide " also give the reaction. Since the boranes can be prepared by the hydroboration of alkenes (15-16), this is an indirect method for the addition of NH3 to a double bond with anti-Markovnikov orientation. Secondary amines can be prepared by the treatment of alkyl- or aryldichloroboranes or dialkylchlorobor-anes with alkyl or aryl azides. 

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

Amines from boranes. A sequential reaction of RBH with BClj and an organic azide leads to the amine with retention of configuration. The following equation illustrates a stereoselective approach to cycloalkylamines on the basis of organoborane... 

Intramolecular reaction of the organoborane with an azide provides a cyclic amine product. For example, in a synthesis of the cyclic hexapeptide echinocandin D, stereoselective hydroboration of the alkene 19 was followed by cyclization to give the substituted pyrrolidine 20 (5.28). ... 

An analogous reaction is the conversion of olefins into primary amines by the consecutive action of BH3. THF and trimethylsilyl azide. The observation that organoboranes and chloramine give primary amines is the basis of an amine synthesis in which olefins are treated with the complex BH3 THF, followed by aqueous ammonia and aqueous sodium hypochlorite. Imines are reduced by the chiral dioxaborolidine 162 to yield optically active amines. 1-Imino-l-phenylpropane, for instance, affords 1-phenylpropylamine in 73% enantiomeric excess (equation 59). ... 

An innovative application of these concepts is to be found in Evans synthesis of the potent antifungal agent echinocandin D (68, Scheme 7.11) [27]. When 65 is treated with dicyclohexylborane, diastereoselective hydroboration is followed by reaction of the azide with the organoborane intermediate, resulting in a ring-contraction and the formation of 67 as the sole diastereomer. 

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