Unsymmetrical hydroborated

Unsymmetrical functional tetraorganotins are generally prepared by tin hydride addition (hydrostaimation) to functional unsaturated organic compounds (88) (see Hydroboration). The realization that organotin hydrides readily add to atiphatic carbon—carbon double and triple bonds forming tin—carbon bonds led to a synthetic method which does not rely on reactive organometatiic reagents for tin—carbon bond formation and, thus, allows the synthesis of... 

Unsymmetrical cleavage of B2H by metal hydrides gives metal tetrahydroborate salts, also called metal borohydrides or hydroborates. 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Tripylborane is an interesting reagent which resembles thexylborane. One of the important uses of thexylborane lies in the synthesis of unsymmetrical thexyldialkylboranes which can then be used in the synthesis of unsymmetrical ketones. However, the reaction is only successful if the alkene used in the first hydroboration step is an internal alkene. Simple terminal alkenes such as 1-hexene react too rapidly with the initially formed thexylmonoalkylborane to allow the reaction to be stopped at that stage. Therefore, mixtures of products result (ref. 27). 

Alkylboranes can be coupled by treatment with silver nitrate and base." Since alkylboranes are easily prepared from alkenes (15-16), this is essentially a way of coupling and reducing alkenes in fact, alkenes can be hydroborated and coupled in the same flask. For symmetrical coupling (R = R ) yields range from 60 to 80% for terminal alkenes and from 35 to 50% for internal ones. Unsymmetrical coupling has also been carried out, but with lower yields. Arylboranes react similarly, yielding biaryls. The mechanism is probably of the free-radical type. 

The formation of unsymmetrical ketones can also be done starting with IpcBCl2. Sequential reduction and hydroboration are carried out with two different alkenes. The first reduction can be done with (CH3)3SiH, but the second stage requires LiAlH4. 

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

With unsymmetrical alkenes, hydroboration occurs so that boron becomes attached to the less-substituted end of the double bond ... 

The hydroboration of an olefin involves a cis addition of a boron-hydrogen bond to an alkene linkage, and for unsymmetric olefins occurs in a counter-Markownikoff fashion. 1-Alkenes and simple 1,2-disubstituted olefins undergo rapid conversion to the corresponding trialkylborane, whereas addition of diborane to tri- and tetrasubstituted olefins may be conveniently terminated at the respective di- and monoalkylborane stage. 1-Alkenes yield trialkylboranes in which there is a preponderant (approximately 94%) addition of the boron atom to the terminal carbon.2,3... 

Substituted diboranes derived from the hydroboration of 1,3-butadiene l,2-tetramethylenediborane(6), 1 and l,2-bis(tetramethylene)-diborane(6), 2 undergo symmetrical and unsymmetrical cleavage reactions 12). 

Scheme 12. Allylic C-H activation via hydroboration of unsymmetrical cyclic tetrasubstituted alkenes.

Unsymmetric alkenes, which carry more alkyl substituents at the center than at the Ca center, are also hydroborated by the unhindered BH3 with considerable regioselectivity... 

The hydroboration of unsymmetrical alkenes thus gives monoalkylboranes (addition of H—BH2), dialkylboranes (addition of H—BHR), or trialkylboranes (addition of H—BR2), which are typical anti-Markovnikov products. Therefore, the reaction sequence hydrobora-tion/oxidation/hydrolysis brings about the anti-Markovnikov addition of H20 to unsymmetrically substituted alkenes. 

V-trimethylsilyl protected olefinic amines and terminal diolefins have been successfully hydroborated with dimethylborane. The resulting organoborane was treated with in situ-generated chloramine or chloralkylamine to produce isomerically pure diamines or N-substituted unsymmetrical diamines in good yields [26] (Scheme 9). 

Thexylborane adds to hindered olefins only once, and the product hydroborates only unhindered olefins thus leading to mixed trialkylboranes. This selective stepwise hydroboration with thexylboranes gives a simple synthesis of unsymmetrical ketones after carbonylation (Eqs. 19 and 20)41-58,59). 

The nitrogen atom in A3-piperideines would be expected to influence the addition of unsymmetrical reagents to the double bond. Although this effect has not been extensively studied, the results on the hydroboration-oxidation of a number of N- substituted A3-piperideines show a preference for the piperidin-3-ol (Scheme 16) (70JOC802). Initial coordination of borane with the nitrogen atom was proposed and the observed regiochemistry is believed to be the result of electronic factors (70TL1133). 

CH,),QH,]2BH (1). Mol. wt. 250.20, m.p. 68°, air stable, in 70% yield by reduction of fluorodimesitylborane with LiAlHj. This borane is recommended for hydroboration of alkynes, par-e hydroboration of unsymmetrical alkynes (equation I). 1-Alkynes khydes in high yield. Since alkcnes react only slowly with this iwration of alkynes in the presence of alkenes is possible. 

Hydroboration of allenes. With few exceptions, the 9-BBN hydroboration of allenes affords B-allylic-9-BBN derivatives. In contrast, the reactions of allenes with disiamylborane or dicyclohexylborane afiord predominantly vinylic boranes. With unsymmetrical allenes, 9-BBN binds to the less substituted carbon atom. Allene itself affords a 1,3-dibora derivative. The B-allylic-9-BBN derivatives are useful reagents for the allylic boration of carbonyl compounds. ... 

Selective Hydroboration and Synthetic Utility of Organoboranes Thus Obtained TaMe 3. Synthesis of Unsymmetrical Ketones via Thexyldialkylboranes... 

Later, Brown and co-workers developed the method described above for the preparation of enantiomerically pure Ipc2BH (>99% ee) and applied the reagent in the asymmetric hydroboration of prochiral alkenes. Oxidation of the trialkylboranes provided optically active alcohols. In the case of cis-alkenes, secondary alcohols were obtained in excellent enantiomeric purity (Figure 1). The reaction is general for most types of cw-alkene, e.g. C(S-2-butene forms (R)-2-butanol in 98.4% ee, and c(s-3-hexene is converted to (R)-3-hexanol in 93% ee. However, the reagent is somewhat limited in reactions with unsymmetrical alkenes e.g. c/s-4-methyl-2-pentene yields 4-methyl-2-pentanol with 96% regioselectivity but only 76% ee (Figure 1). ... 

Hydroboration is regioselective. With unsymmetrical alkenes, the boron atom bonds to the less substituted carbon atom. For example, addition of BH3 to propene forms an alkylborane with the B bonded to the terminal carbon atom. 

In the case of unsymmetrical alkynes the regioselectivity is only modest. Use of excess borane-THF results in dihydroboration. Many of the problems encountered in hydroboration reactions of borane-THF can be overcome by the use of more selective reagents such as dialkylboranes or dihaloboranes. 

Unsymmetrical, nonconjugated dienes are generally easier to monohydroborate because of intrinsic differences between the two double bonds. Both 9-BBN-H and disiamylborane favor attachment to a terminal double bond rather than an internal double bond (e.g. equation 32). On the other hand, 2-methyl-1, S-hexadiene reacts predominantly at the 1-position with 9-BBN-H and almost exclusively at the 6-position with disiamylborane. The products of dihydroboration of a,o>-dienes with 9-BBN-H can be redistributed with borane-dimethyl sulfide to give boracyclanes. In this way, some of the problems sometimes associated with direct hydroboration of dienes with borane (see Section 3.10.2.1) may be overcome. 

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