Addition reactions hydroboration-oxidation

The addition of H2 or a peroxyacid to an alkene is a syn addition reaction hydroboration-oxidation is overall a S5U1 addition of water. 

From A17(20)-Olefins The addition of an oxygen function to C-20 is best accomplished by the hydroboration-oxidation reaction on a A17(20) olefin. The ready preparation of such olefins has been discussed earlier predominantly m-olefins are obtained via the Wittig reaction on 17-keto steroids, and the /ra/w-olefins via dehydration reactions. Hydroboration-oxidation of m-A17(20)-olefins gives the 20a-alcohol in high yield, presumably by attack of diborane on the a-side of the double bond 137... 

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. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Z-vinyl iodide was obtained by hydroboration and protonolysis of an iodoalkyne. The two major fragments were coupled by a Suzuki reaction at Steps H-l and H-2 between a vinylborane and vinyl iodide to form the C(ll)-C(12) bond. The macrocyclization was done by an aldol addition reaction at Step H-4. The enolate of the C(2) acetate adds to the C(3) aldehyde, creating the C(2)-C(3) bond and also establishing the configuration at C(3). The final steps involve selective deprotonation and oxidation at C(5), deprotection at C(3) and C(7), and epoxidation. 

Figure 11.1 The hydroboration-oxidation of 1-methylcyclopentene. The first reaction is a syn addition of borane. (In this illustration we have shown the boron and hydrogen both entering from the bottom side of 1-methylcyclopentene. The reaction also takes place from the top side at an equal rate to produce the enantiomer.) In the second reaction the boron atom is replaced by a hydroxyl group with retention of configuration. The product is a trans compound (trans-2-methyl-cyclopentanol), and the overall result is the syn addition of -H and -OH.

The uncatalyzed hydroboration-oxidation of an alkene usually affords the //-Markovnikov product while the catalyzed version can be induced to produce either Markovnikov or /z/z-Markovnikov products. The regioselectivity obtained with a catalyst has been shown to depend on the ligands attached to the metal and also on the steric and electronic properties of the reacting alkene.69 In the case of monosubstituted alkenes (except for vinylarenes), the anti-Markovnikov alcohol is obtained as the major product in either the presence or absence of a metal catalyst. However, the difference is that the metal-catalyzed reaction with catecholborane proceeds to completion within minutes at room temperature, while extended heating at 90 °C is required for the uncatalyzed transformation.60 It should be noted that there is a reversal of regioselectivity from Markovnikov B-H addition in unfunctionalized terminal olefins to the anti-Markovnikov manner in monosubstituted perfluoroalkenes, both in the achiral and chiral versions.70,71... 

In this chapter, theoretical studies on various transition metal catalyzed boration reactions have been summarized. The hydroboration of olefins catalyzed by the Wilkinson catalyst was studied most. The oxidative addition of borane to the Rh metal center is commonly believed to be the first step followed by the coordination of olefin. The extensive calculations on the experimentally proposed associative and dissociative reaction pathways do not yield a definitive conclusion on which pathway is preferred. Clearly, the reaction mechanism is a complicated one. It is believed that the properties of the substrate and the nature of ligands in the catalyst together with temperature and solvent affect the reaction pathways significantly. Early transition metal catalyzed hydroboration is believed to involve a G-bond metathesis process because of the difficulty in having an oxidative addition reaction due to less available metal d electrons. 

The overall result of the sequence hydroboration + oxidation is a regioselective anh-Markownikoff-addition of water to an alkene. This reaction is an important method in organic synthesis, since it can be made stereoselective and even enantioselective. 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

The advantages of a hydroboration-oxidation sequence to prepare alcohols are simplicity of procedure relatively mild reaction conditions high overall yields absence of skeletal rearrangements production of carbinol in which there is an overall cis addition of water to a double bond in a counter-Marknowikoff sense. 

This section covers the hydroboration-oxidation of alkenes to give alcohols. The author chooses to include this under oxidation since an oxygen atom is introduced into the molecule. This reaction can be performed in a stereocontrolled fashion and it is these methods that are highlighted here. In addition, one similar reductive-oxidation reaction is included, since it is an extremely facile route to benzyl alcohols and a-hydroxyalkanoic acids. 

The anti-Markovnikov s addition results from a hydroboration-oxidation reaction. 

The hydroboration/oxidation/hydrolysis of trisubstituted alkenes also takes place as a cis-addition. The reaction equation from Figure 3.25 shows this using 1-methylcyclo-hexene as... 

The stereochemical result is no longer characterized solely by the fact that the newly formed stereocenters have a uniform configuration relative to each other. This was the only type of stereocontrol possible in the reference reaction 9-BBN + 1-methylcyclohexene (Figure 3.25). In the hydroborations of the cited chiral alkenes with 9-BBN, an additional question arises. What is the relationship between the new stereocenters and the stereocenter(s) already present in the alkene When a uniform relationship between the old and the new stereocenters arises, a type of diastereoselectivity not mentioned previously is present. It is called induced or relative diastereoselectivity. It is based on the fact that the substituents on the stereocenter(s) of the chiral alkene hinder one face of the chiral alkene more than the other. This is an example of what is called substrate control of stereoselectivity. Accordingly, in the hydroborations/oxidations of Figures 3.26 and 3.27, 9-BBN does not add to the top and the bottom sides of the alkenes with the same reaction rate. The transition states of the two modes of addition are not equivalent with respect to energy. The reason for this inequality is that the associated transition states are diastereotopic. They thus have different energies—just diastereomers. 

The conclusion drawn from Section 3.4.1 for the hydroborations to be discussed here is this an addition reaction of an enantiomerically pure chiral reagent to a C=X double bond with enantiotopic faces can take place via two transition states that are diastereotopic and thus generally different from one another in energy. In agreement with this statement, there are diastereoselective additions of enantiomerically pure mono- or dialkylboranes to C=C double bonds that possess enantiotopic faces. Consequently, when one subsequently oxidizes all C— B bonds to C—OH bonds, one has realized an enantioselective hydration of the respective alkene. 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

The hydroboration/oxidation/hydrolysis of trisubstituted olefins also takes place as a cis addition. The reaction equation from Figure 3.19 shows this using 1-methylcyclo-hexene as an example. 9-BBN adds to both sides of its C=C double bond at the same reaction rate. In the energy profile this fact means that the activation barriers for both modes of addition are equally high. The reason for this equality is that the associated transition states are enantiomorphic. They thus have the same energy—just as enan-tiomorphic molecules. 

A reaction in which one direction of bond making or bond breaking occurs preferentially over all other directions. For example, the addition of HC1 is regioselective, predicted by Markovnikov s rule. Hydroboration-oxidation is regioselective because it consistently gives anti-Markovnikov orientation, (p. 332)... 

Hydroboration-Oxidation In Section 8-7 we saw that hydroboration-oxidation adds water across the double bonds of alkenes with anti-Markovnikov orientation. A similar reaction takes place with alkynes, except that a hindered dialkylborane must be used to prevent addition of two molecules of borane across the triple bond. Di(second-ary isoamyl)borane, called disiamylborane, adds to the triple bond only once to give a vinylborane. (Amyl is an older common name for pentyl.) In a terminal alkyne, the boron atom bonds to the terminal carbon atom. 

Complexes of cationic rhodium compounds with asymmetric phosphane ligands catalyze the hydroboration of prostereogenic alkenes with catecholborane (see Section D.2.5.2.1.4.). The product alcohols are of 7-96% cc (Table 3). Enantioselectivity is excellent for the hydroboration/oxidation of styrenes but low for stilbenes. The small number of examples studied to date precludes generalizations, however, compared to the uncatalyzed reaction, opposite regioselec-tivity is observed for the addition to styrenes. 

As was already mentioned, the standard procedure for acid catalyzed alkene hydration exhibits a rather low selectivity. On the other hand, the use of a hydroxymercuration-reduction sequence leads to the exclusive formation of Markovnikov s alcohols. A nearly exclusive anti-Markovnikov s hydration is achieved via a hydroboration-oxidation reaction (see Section 2.4). The result in both these cases is the net addition of H2O, but the basic differences in the reaction mechanisms unambiguously determine a reversed regioselectivity pattern. 

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