Basicity Borane amines

Steric interactions between bulky substituents such as t-Bu, leading to larger C-E-C bond angles, obviously affect the Lewis basicity caused by the increased -character of the electron lone pair. However, the strength of the Lewis acid-base interaction within an adduct as expressed by its dissociation enthalpy does not necessarily reflect the Lewis acidity and basicity of the pure fragments, because steric (repulsive) interactions between the substituents bound to both central elements may play a contradictory role. In particular, adducts containing small group 13/15 elements are very sensitive to such interactions as was shown for amine-borane and -alane adducts... 

The complexes of borane (BH3) itself with amines, phosphines, dialkyl sulfides and carbon monoxide, the first representatives prepared only in die 1930s were thoroughly discussed in several books and reviews.2,9,25-36 Therefore, in this section, only a brief summary will be given outlining the most basic aspects of these compounds, whereas complexes of substituted boranes will be discussed in more detail. 

Many phosphine-borane complexes Y3P BZ3 have been characterized. They include compouuds where Y = alkoxy, aUcyl, amino, halide, and hydride groups, and Z = alkyl, halide, and hydride. The stabilities of these complexes vary widely depending on the Lewis acidity and basicity of the boron and phosphorus moieties, respectively. The relative stabilities of Lewis acid-base complexes with BH3 are R3P > R3N > R3AS > R3Sb, but with BF3 the order is R3N > R3P > R3AS > RsSb. The stabihties of the borou halide complexes of phosphines follow the same order as the amine complexes BI3 > BBrs > BCI3 > BF3. 

A dry 50-mL flask equipped with septum inlet, reflux condenser, and magnetic stirrer is flushed with N2. The flask is charged with 12 mL of DME and 12 mmol of dich]oro[(lS,2S)-2-methylcyclopentyl]borane-dimethyl sulfide complex. The solution is heated to 60 °C and attached to a gas burette. Then, 1.4 g (13 mmol) of cyclopentyl azide is added dropwise (ca. 2 h) and the evolved N2 is measured. After the addition is complete, the solution is stirred for an additional 30 min. Gas evolution has ceased at this point. The solution iscooled toO°C and very carefully hydrolyzed by slowly adding 10 mL of H,0 (exothermic ). Then the mixture is made strongly basic with 40% KOH. The liberated amine is extracted with Et20. The ether solution is dried over anhyd K2C03 and the solvent is removed at reduced pressure. On distillation, 1.2 g (72%) of the amine are collected, bp 100 CC/15 Torr. The amine is further purified as its hydrochloride salt, mp 159-160 aC [a] 3 +39.13 (c = 10, CH3OH). 

Boric acid may be similarly reduced to BjH under basic conditions on a large scale. Hydrogen in the presence of Al reduces borates to boranes quantitatively. These bo-ranes are trapped as the amine borane, e.g., phenylborate is dissolved in triethylamine and to the solution is added activated Al powder and small amounts of AICI3 catalyst. The mixture is agitated at 180°C for 1 h at 14.2 MPa of Hj. Quantitative yields of the (CH3)3NBH3 species are available from this process with a lower yield of C5N5N(CH3)2BH3 ... 

B-strain can occur in amines to lower their basicity. Will B-strain inhibit or enhance the acidic behavior of boranes ... 

Hoffmann et al have reported the addition of allyl(dimethoxy)borane to linear and branched a-aryl-aldimines (entries 16-19, Table 2). The absence of a-deprotonation may be explained by a delicate balance between the basicity and the reactivity of the allylboronate. Allyl(dimethoxy)borane should thus be considered the reagent of choice in reactions with enolizable aldimines. Reactions are conveniently carried out at 25 °C in CH2CI2 and work-up is performed using triethanolamine to break up amine-boronate complexes. Allyl(dimethoxy)borane also adds to the cyclic imine, A -piperideine, in 90% yield. The reported yields for the addition of allyllithium and allylmagnesium chloride to A -piperideine are low. 

Dimethylamine-borane is a white crystalline compound, soluble in many organic solvents, as are other amine-boranes. Unlike most borane adducts of tertiary amines and phosphines, it is also soluble in water. The vapor pressure of the adduct is 0.1 torr at 25°.10 The compound is reasonably stable in neutral or basic aqueous solution at room temperature but decomposes in acidic solution. On heating, dimethylamine-borane loses hydrogen to form dimethylamino-borane.11... 

The addition reaction of carbon-11 labelled cyanide ion to the bisulphite addition adduct of an aldehyde has been extended to prepare carbon-11 labelled amines. Maeda and coworkers prepared both p- and m-octopamine [2-(p-and m-hydroxyphenyl)-2-hydroxyethyl-amine] from the corresponding benzaldehyde by reducing the cyanohydrin formed in the reaction between the appropriate benzaldehyde and cyanide ion both under enzymatic conditions and by the basic modification of the Bucherer-Strecker synthesis, with borane-THF. The synthesis of / -octopamine is presented in equation 64. 

A-Alkylation Reactions. The 9-BBN complexes of diamines such as 1,8-diaminonaphthalene and 2-aminobenzylamine serve as substrates for selective iV-alkylation. N-chelated borane complexes undergo regioselective mono-(V-alkylation with an alkyl halide under basic conditions without further alkylation. Hydrolysis of the corresponding intermediate provides the mono-iV-alkyl-ated product in excellent yields (eq 53). In this case, the 9-BBN chelation of the diamine both protects the aromatic amine and activates the benzylic amine. 

Phosphine boranes would not be so popular if the borane group could not be easily removed. Two reliable methods have been developed. The first one is the treatment of phosphine boranes with amines (D) or alcohols, which act as borane acceptors. Although phosphine boranes are in general more stable than amine boranes, the presence of a large excess of a basic amine frequently suffices to displace the equilibrium and deprotect completely the phosphine. Typical amines used for this transformation are diethylamine, TMEDA, pyrrolidines, morpholine and DABCO. The reactions are usually carried out at room temperature or with moderate heating in neat amine with the exception of DABCO, which as it is a solid is typically used in toluene. 

The synthetic uses of the acid-promoted decomposition of a-diazoketones have been reviewed.A comparative study of methods for the synthesis of optically pure N-protected a-aminoaldehydes concludes that borane-THF is the reagent of choice for the reduction of N-protected amino-acids to the amino-alcohol without racemization, and that pyridinium dichromate is satisfactory for the subsequent oxidation to the aldehyde. Since the reaction between amines and a-haloketones is sometimes a poor method for the preparation of a-alkylaminoketones, the far less basic imidates have been developed as effective nucleophilic components in this reaction [equation (51)]. a-Aminoketones can also be prepared via Wittig rearrangement of iminoethers [equation (52)], ° or by a-aminomethylation of aldehydes [equation (53)]. ... 

An efficient one-pot procedure for the iV-monomethylation of primary amines has been reported the method involves formylation with acetic formic anhydride followed by borane methyl sulphide reduction. The reaction sequence is applicable to even very weakly basic and sterically hindered amines, and the products are uncontaminated by over-alkylation. In addition, the transition-metal-catalysed j V-monoalkylation of amines by alcohols has been previously reported (c/. Vol. 6, p. 198) as a method to overcome problems associated with over-alkylation. A similar procedure for the preparation of unsymmetrical secondary (and tertiary) amines utilises a ruthenium catalyst, and is particularly suitable for the synthesis of cyclic amines. ... 

Even though this concept has been proven to be effective, the toxicity of NaCNBHj led to the search for alternative reagents whereby amine-boranes turned out to be competent substitutes [117]. They are stable in water at neutral or basic pH and soluble and unreactive toward a wide range of protic and aprotic solvents. Deracemization of several natural and nonnatural AAs with an L-amino acid deaminase (l-AAD)... 

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