Trialkylboranes transformation reactions

Enantiopure benzylamines are important intermediates in the synthesis of pharmaceutically active compounds and chiral ligands for asymmetric transformations. Fernandez and co-workers ° reported that primary and secondary benzylamines could be obtained in moderate yields by converting the initially formed catecholboronate ester into a trialkylborane by reaction with either diethylzinc or methylmagnesium chloride, followed by treatment of the trialkylborane thus obtained with hydroxylamine-O-sulfonic acid, which yielded primary benzylamine 291. When the trialkylborane was treated with A-substituted chloramines, a secondary benzylamine, e.g., 292, was formed. A variety of vinylarenes gave the corresponding benzylamines in moderate to good yields and good-to-excellent enantioselectivity (78-98% ee). 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

In the interim period, results have accumulated steadily, in endeavors to address and extend the chemistry beyond the initial perceived limitations. These limitations include the following (a) the effective catalytic syntheses are confined to the reactions utilizing catecholborane (b) the scope of alkenes for which efficient rate, regio- and enantio-selectivity can be achieved is limited, and (c) the standard transformation mandates the oxidation of the initially formed (secondary) boronate ester to a secondary alcohol, albeit with complete retention of configuration [8]. Nonetheless, for noncatalytic hydroboration reactions that lead to the formation of a trialkylborane, a wide range of stereo-specific transformations may be carried out directly from the initial product, and thereby facilitate direct C-N and C-C bond formation [9]. 

A unique reaction of formyl complexes is formyl transfer," in which the formyl ligand undergoes apparent migration from one metal to another. This transformation was first observed with the manganese formyl 12, as shown in Eq. (19) (35, 47). However, 12 is unstable at room temperature and cannot be separated from trialkylborane by-product. Therefore, it is again important to establish that this type of reaction proceeds with pure formyl complexes. 

Borane transforms a wide range of alkenes into trialkylboranes under mild conditions but the trifunctional nature of borane and its trialkylborane products imposes some limitations on its use. Many of the synthetically useful reactions of the trialkylboranes (see Chapters B.2 and B.3) use all three alkyl substituents, but some reactions only utilize either two or even one of the alkyl substituents. This sets a maximum yield (based on the alkene starting material) for these latter transformations of 66% and 33% respectively which is clearly undesirable especially if the alkene involved is the product of a multi-step synthetic sequence. To overcome this problem, and others such as the production of intractable polymers on addition of borane to dienes and alkynes, monoalkylborane and dialkylborane hydroborating reagents were introduced. Some commonly used reagents are depicted in Figure B 1.2 and two are described in more detail below. 

The reaction of MVL with trialkylboranes gave vinyl borate salts 536, which suffer alkyl migration at room temperature to give salts 537. These compounds can be transformed into vinyl ethers or methyl ketones by oxidation with hydrogen peroxide (Scheme 144)819. 

Niedenzu initiated studies of B-substituted analogs of (47) and (48) and various X = chloro, fluoro, alkyl, aryl, alkoxy, and amido derivatives of (49). These compounds should be very useful for further synthetic transformations. Koster and coworkers have examined the reactions of sterically congested pyrazoles with (9H-9-BBN)2 and unique neutral, monomeric products with tricoordinate boron centers (50) are obtained. The compounds are stable toward dimerization. When bulky pyrazoles are allowed to react with activated trialkylboranes, for example, BEts at 170 °C,... 

The trialkylborane 53 is converted to alcohol 54 by reaction with an aqueous solution containing OH and H202 (Scheme 4.12). Inspection of the structures of the alkene 44 and the alcohol 54 shows that addition of water has taken place in an anti-Markovnikov sense in particular, hydrogen has now been added to the more alkylated carbon. One important feature of the hydroboration is transformation of 53 into 54, which occurs with retention of configuration. Scheme 4.12... 

A pressure of 70 atmospheres of CO is required since hindered boranes, especially thexylborane, react sluggishly at atmospheric pressure. However, thexylborane reacted with cyclopentene to generate 188, and subsequent reaction with O-acetyl-hept-6-en-l-ol gave the trialkylborane (189). Carbonylation in the presence of water followed by oxidation gave the mixed ketone (190) in 73% yield. 33 In a similar manner, dienes can be transformed into the corresponding cyclic ketones. 34,135... 

A second means of effecting alkylations of organoboranes involves reactions with highly reactive alkyl halides, especially a-halocarbonyl compounds. For example, ethyl bromoacetate has been found to alkylate a number of trialkylboranes in excellent yield. This synthetic transformation is more efficiently carried out using a... 

It would be presumptuous to attempt to summarize fully the utility of the hydroboration reaction here. There are many variations of this reaction, each designed to accomplish a specific synthetic transformation. A book could be written on the subject. In fact, Professor H. C. Brown has written just such a book. We ll only mention one especially important reaction here, one that leads to a new process for the synthesis of alcohols (recall Problem 9.13, p. 390). When one molecule of trialkylborane is treated with hydrogen peroxide (H2O2) and hydroxide ion (HO ), three molecules of an alcohol are formed along with boric acid (Fig. 9.66). 

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