Hydroboration anti-Markovnikov-addition product

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. 

In hydroboration reactions with vinylsilanes, the addition of the boron atom can take place at the end carbon atom of the vinyl moiety (anti-Markovnikov addition) or at the carbon atom bonded to the silicon atom (Markovnikov addition), as shown in Scheme 2. Under the employed conditions the anti-Markovnikov product was formed predominantly. 

Reactions can be run to give the opposite of the expected product, yielding what is called anti-Markovnikov addition. That is, hydrogen ends up on the more substituted carbon of the double bond. The hydroboration/oxidation reaction yields this, as do reactions that are conducted in peroxides. 

It is important to recognize that this reaction gives products corresponding to anti-Markovnikov addition of water to the carbon-carbon double bond. This behavior evidently results because carbonium ions are not intermediates - rearrangement does not occur in hydroboration. The stereochemistry of this reaction involves syn addition, that is, addition to the double bond is on the same face of the alkene. 

A. special note should he made concerning hydriition reactions of tilkynes. Remember that hydration of alkencs leads to alcohols. Alkynes can be hyilraied. too. Markovnikov addition is achieved with an aqueous acidic Hg(ll) catalyst. Anti-Markovnikov addition occurs vi i a modified hydroboration-o.xidation sequence. Both initially give vinylic alcohols (or cnols) as products, but these are kinetieally and thermodytiamically unstable and i.sonieri/e to carbonyl compounds in a reaction called lautomerism. 

By considering the reactions depicted in Schemes 10.3 and 10.4, you can see how the hydroboration-oxidation of an alkene gives an alcohol that is the product of overall anti-Markovnikov addition of the elements of H-OH to the carbon-carbon double bond. Remember, however, that the key step determining the regio-chemistry of the reaction is the Markovnikov addition of the hydrogen-boron bond across the Tr-bond. 

Our previous method for alcohol synthesis, hydration of aikenes, necessarily produced the more substituted alcohol. So now we have complementary synthetic methods for producing hoth possible alcohols from a given alkene (Fig. 9.69). Direct hydration gives the more substituted product (Markovnikov addition) and the indirect hydroboration/oxidation method gives the less substituted alcohol (anti-Markovnikov addition). Be sure to add these reactions to your file-card collection of synthetically useful reactions. 

Hydroboration/oxidation is a process that yields an alcohol that is the product of overall anti-Markovnikov addition. The mechanism of hydroboration is complex, but several lines of evidence have led to the picture we have of a concerted reaction with an unsymmetrical transition state in which one of the alkene s carbon atoms becomes partially positively charged (Figs. 9.55-9.60). The synthetic utility of this reaction is not complex at all. For unsymmetrical aikenes, hydroboration/oxidation leads to the less substituted alcohol. 

Hydroboration/oxidation (p. 390) first generates an alkylborane that subsequently reacts with peroxide in base to give the product of anti-Markovnikov addition. 

As we saw in the case of hydroboration (Section 12-8), anti-Markovnikov additions are synthetically useful because their products complement those obtained from ionic additions. The ability to control regiochemistry is an important feature in the development of new synthetic methods. 

In Summary HBr in the presence of peroxides undergoes anti-Markovnikov addition to terminal alkynes to give 1-bromoalkenes. Hydroboration-oxidation with bulky boranes furnishes intermediate enols that tautomerize to the final product aldehydes. 

Hydroboration-oxidation of alkenes also requires two steps. The sequence of reactions adds the hydrogen and hydroxyl of water to a double bond to give a product that corresponds to anti-Markovnikov addition. 

The conversion to linear alcohol is an anti-Markovnikov addition of water, which is most easily accomplished by hydroboration/oxidation—so our reagents would be (1) BH3 (2) HOO . The branched alcohol is the product of Markovnikov addition of water via the stabilized secondary benzylic carbocation, so our reagent is simply aqueous acid. 

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... 

New mechanistic studies with [Cp2Ti(CO)2] led to the observation that the tita-nocene bis(borane) complex [Cp2Ti(HBcat)2] (Hbcat = catecholborane) generated in situ is the active catalyst.603 It is highly active in the hydroboration of vinylarenes to afford anti-Markovnikov products exclusively, which is in contrast to that of most Rh(I)-catalyzed vinylarene hydroboration. Catecholborane and pinacolborane hydroborate various terminal alkynes in the presence of Rh(I) or Ir(I) complexes in situ generated from [Rh(COD)Cl2] or [Ir(COD)Cl2] and trialkylphosphines.604 The reaction yields (Z)-l-alkenylboron compounds [Eq. (6.107)] that is, anti addition of the B—H bond occurs, which is opposite to results found in catalyzed or uncatalyzed hydroboration of alkynes ... 

Some reactions do not follow Markovnikov s Rule, and anti-Markovnikov products are isolated. This is a feature for example of radical induced additions of HX and of Hydroboration. 

The epoxidation-epoxide opening sequence with this reagent provides a convenient access to the products of an //-Markovnikov addition of water to olefins. Interestingly, the Cp2TiCl/H20 couple combination shows anti stereoselectivity in the reduction step [73, 74], which is complementary to the hydroboration-oxidation method (Scheme 32). 

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). ... 

Like alkylboranes, dnylboranes can be converted into alcohols by treatment with basic peroxide (Fig. 10.75).The products are ends in this case, and they are in equilibrium with the corresponding carbonyl compounds. Here s an important point The regiochemistry of this reaction is the opposite of the regiochemistry of the hydration reaction of alkynes. This situation is exactly the same as the one that exists with the alkenes Hydration of an alkene gives overall Markovnikov addition, whereas the hydroboration/oxidation sequence gives the anti-Markovnikov product. 

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... 

Alkenes can be converted into primary alkyl acetates via titanium-catalysed hydroalumination (Scheme 2) followed by lead tetra-acetate oxidation of the dialkyldihydroaluminate addition products (2). Only two equivalents of alkene are used per aluminium atom as it seems that only two alkyl groups from the aluminates can participate in the oxidation. In a closely related study a titanium-boron complex has been found to promote catalytic hydroboration of alkenes (also Scheme 2) cw-addition predominates for non-terminal alkenes. The adducts (3) can be oxidized to alcohols, and it may be seen that both sequences provide anti-Markovnikov products. 

In hydrozirconation with Schwartz s reagent, Cp2ZrHCl, addition to alkenes leads to the anti-Markovnikov all l (Eq. 14.39). Remarkably, 1-, 2-, and 3-hexene all give the same n-hexyl product The reastm must be that the initially formed alkyls rapidly )9-eliminate. This moves the C=C bond along the chain in an alkene isomerization reaction (Section 9.1), until the n-hexyl complex is formed. This must therefore be the thermodynamically most stable alkyl. In general, primary alkyls tend to be most stable, probably because they are the least bulky isomer. In hydroboration, in contrast, no isomerization is observed. 

Hydroboration, the addition of B-H bonds to carbon-carbon multiple bonds, is an attractive route to organoboranes, which can be converted into a variety of functional groups such as alcohols upon alkaline hydrogen peroxide treatment to give the corresponding anti-Markovnikov products. Metal catalysts allow for these hydroborations to be carried out under milder reaction conditions, improved or even altered reaction selectivity and more importantly, enantioselectively. 

Radicals, lacking a closed outer shell of electrons, are capable of reacting with double bonds. However, a radical requires only one electron for bond formation, unlike the electrophiles presented in this chapter so far, which consume both electrons of the tt bond upon addition. The product of radical addition to an alkene is an alkyl radical, and the final products exhibit anti-Markovnikov regiochemistry, similar to the products of hydroboration-oxidation (Section 12-8). 

---