Oxidation reactions Brown hydroboration reaction

The Brown hydroboration reaction is the addition of B-H across a n-system (1) in an anti-Markovnikov fashion. Most commonly, this reaction utilizes BH3 THF as the hydroborating reagent and is followed by an oxidation of the newly formed C-B bond to afford an alcohol product (2). ... 

The hydroboration reaction is generally highly, but not completely, regioselective. For example, reaction of 1-hexene (47) with diborane, followed by oxidation, produces 1-hexanol (48) in high yield, with only a small amoimt of 2-hexanol (49, equation 9.46). Brown determined that the preference for the boron atom to add to the less-substituted carbon atom is about 94% for monosubstituted alkenes such as 1-pentene, 99% for em-disubstituted al-kenes such as 2-methyl-l-butene, and 98% for trisubstituted alkenes such as 2-methyl-2-butene. ... 

Brown et a/ [1] have elegantly hydroborated a variety of heterocyclic olefins, which on oxidation yield the corresponding alcohols in excellent yields. In the case of heterocyclic olefin containing a double bond a to the heteroatom, the hydroboration reaction is highly regioselective, placing boron at the (3-carbon atom. The use of 9-BBN for the synthesis of variety of heterocyclic alcohols is given in Chart 6.21. 

In addition to the oxymercuration method, which yields the Markovnikov product, a complementary method that yields the non-Markovnikov product is also useful. Discovered in 1959 by H. C. Brown and cailed hydroboration, the reaction involves addition of a B-H bond of borane, BH3, to an alkene to yield an organoborane intermediate, RBH2. Oxidation of the organoborane by reaction with basic hydrogen peroxide, H2O2, then gives an alcohol. For example ... 

Hydroboration, the addition of a boron-hydrogen bond across an unsaturated moiety, was first discovered by H. C. Brown in 1956. Usually, the reaction does not require a catalyst, and the borane reagent, most commonly diborane (B2H6) or a borane adduct (BH3-THF), reacts rapidly at room temperature to afford, after oxidation, the /AMarkovnikov alkene hydration product. However, when the boron of the hydroborating agent is bonded to heteroatoms which lower the electron deficiency, as is the case in catecholborane (1,3,2-benzodioxaborole) 1 (Scheme 1), elevated temperatures are needed for hydroboration to occur.4 5... 

The work of H. C. Brown has made hydroboration an enormously useful synthetic reaction. Oxidation of the adduct with alkaline hydrogen peroxide removes the boron smoothly without rearrangement and replaces it by a hydroxy group. The oxidation proceeds entirely with retention of configuration. For example, the product of Reaction 7.19 is converted by oxidation to trans-2-methylcyclopentanol in high yields (Equation 7.20). 

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 of alkenes yields alkylboranes, and these, we have seen (Sec. 15.9), can be converted through oxidation into alcohols. But oxidation is only one of many reactions undergone by alkylboranes. Since the discovery of hydroboration in 1957, H. C. Brown and his co-workers (p. 507) have shown that alkylboranes are perhaps the most versatile class of organic reagents known. 

An atom or a molecule does not have to be positively charged to be an electrophile. Borane (BH3), a neutral molecule, is an electrophile because boron has only six shared electrons in its valence shell. Boron, therefore, readily accepts a pair of electrons in order to complete its octet. Thus, alkenes undergo electrophilic addition reactions with borane serving as the electrophile. When the addition reaction is over, an aqueous solution of sodium hydroxide and hydrogen peroxide is added to the reaction mixture, and the resulting product is an alcohol. The addition of borane to an alkene, followed by reaction with hydroxide ion and hydrogen peroxide, is called hydroboration-oxidation. The overall reaction was first reported by H. C. Brown in 1959. 

The reaction in equation 9.52 does not provide a convincing demonstration of the stereochemistry of hydroboration-oxidation, since 52 is thermodynamically more stable than the corresponding cis isomer. Therefore, Brown and Zweifel also carried out the procedure on 1,2-dimethylcyclopentene (53, equation 9.53). The product of that reaction was the less stable stereoisomer... 

Olefin hydroboration, which is the addition of a B-H bond across C=C bond, was first discovered by H. C. Brown in 1956 and Koster in 1958. Typically, the reaction does not require a catalyst and the simple borane reagent (e.g., BHg THF, BH3-SMe2, BH2Cl Et20, thexylborane, disiam-ylborane, and 9-BBN) or boranes bearing electron-withdrawing substituents (e.g.. Piers s borane B(C6p5)2 ) react rapidly even at room temperature to afford, after oxidation, the linear anti-Markovnikov products. The reaction can be remarkably C=C/C=0 chemoselective for terminal alkenes... 

Hydroboration is defined as the addition of borane or one of its derivatives to a multiple bond. It is an enormously versatile reaction synthetically, developed by H.C. Brown in the 1950s and recognized by his Nobel Prize in 1979. We will be looking specifically at the use of a hydroboration-oxidation sequence to accomplish the stereo- and regiospecific anti-Markovnikov addition of water to alkenes. 

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