Chemistry
Hydroboration Oxidation of Alkynes
Hydroboration oxidation of alkynes is a chemical reaction that involves the addition of borane to the carbon-carbon triple bond of an alkyne, followed by oxidation with hydrogen peroxide and a base. This process results in the formation of an enol, which can tautomerize to a ketone or aldehyde. The reaction is a useful method for the synthesis of carbonyl compounds from alkynes.
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11 Key excerpts on "Hydroboration Oxidation of Alkynes"
eBook - PDF- T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
- 2016(Publication Date)
- Wiley(Publisher)
• As a consequence, hydroboration–oxidation gives us a method for the preparation of alcohols that cannot normally be obtained through the acid-catalyzed hydration of alkenes or by oxymercuration–demercuration. For example, the acid-catalyzed hydration (or oxymercuration–demercuration) of 1-hexene yields 2-hexanol, the Markovnikov addition product. H 3 O + , H 2 O 1-Hexene 2-Hexanol OH Markovnikov addition Oxidation of Trialkylboranes A MECHANISM FOR THE REACTION [ [ R H B R R O O R H + B R R O O - - R B R O R H + O - Trialkyl- borane Hydroperoxide ion Unstable intermediate Borate ester The boron atom accepts an electron pair from the hydroperoxide ion to form an unstable intermediate. An alkyl group migrates from boron to the adjacent oxygen atom as a hydroxide ion departs. The configuration at the migrating carbon remains unchanged. Repeat sequence twice B — O — R — R O — R O - - Hydroxide anion attacks the boron atom of the borate ester. An alkoxide anion departs from the borate anion, reducing the formal charge on boron to zero. Proton transfer completes the formation of one alcohol molecule. The sequence repeats until all three alkoxy groups are released as alcohols and inorganic borate remains. O O O Trialkyl borate ester Alcohol R H R H H B + - - H + Hydrolysis of the Borate Ester — R O — R O — R O — R O — R O — R O — R O — R O — R O — B O — B O — B O — R O 8.8 OXIDATION AND HYDROLYSIS OF ALKYLBORANES 357 In contrast, hydroboration–oxidation of 1-hexene yields 1-hexanol, the anti-Markovnikov product. 1-Hexene Anti-Markovnikov addition 1-Hexanol (90%) (1) BH 3 THF OH (2) H 2 O 2 , HO - OH 3-Methyl-2-butanol 2-Methyl-2-butene (1) BH 3 THF (2) H 2 O 2 , HO - • Hydroboration–oxidation reactions are stereospecific; the net addition of − H and − OH is syn, and if chirality centers are formed, their configuration depends on the stereochemistry of the starting alkene.
eBook - PDF- T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
- 2017(Publication Date)
- Wiley(Publisher)
8.8 OXIDATION AND HYDROLYSIS OF ALKYLBORANES 355 8.7B Stereochemistry of Hydroboration • The transition state for hydroboration requires that the boron atom and the hydro- gen atom add to the same face of the double bond: Stereochemistry of Hydroboration B H H H H H H B syn addition + We can see the results of a syn addition in our example involving the hydroboration of 1-methylcyclopentene. Formation of the enantiomer, which is equally likely, results when BH 3 adds to the top face of the 1-methylcyclopentene ring: B + enantiomer anti-Markovnikov with syn addition CH 3 BH 3 CH 3 H H H H H PRACTICE PROBLEM 8.11 Specify the alkene needed for synthesis of each of the following alkylboranes by hydroboration: (a) B (b) B (c) B (d) Show the stereochemistry involved in the hydroboration of 1-methylcyclohexene. PRACTICE PROBLEM 8.12 Treating a hindered alkene such as 2-methyl-2-butene with BH 3 :THF leads to the for- mation of a dialkylborane instead of a trialkylborane. When 2 mol of 2-methyl-2-butene is added to 1 mol of BH 3 , the product formed is bis(3-methyl-2-butyl)borane, nicknamed “disiamylborane.” Write its structure. Bis(3-methyl-2-butyl)borane is a useful reagent in certain syntheses that require a sterically hindered borane. (The name “disiamyl” comes from “disecondary-iso-amyl,” a completely unsystematic and unacceptable name. The name “amyl” is an old common name for a five-carbon alkyl group.) 8.8 OXIDATION AND HYDROLYSIS OF ALKYLBORANES The alkylboranes produced in the hydroboration step are usually not isolated. They are oxidized and hydrolyzed to alcohols in the same reaction vessel by the addition of hydro- gen peroxide in an aqueous base: R 3 B → H 2 O 2 , aq. NaOH, 25 °C Oxidation and hydrolysis 3R − OH + B(ONa) 3 356 CHAPTER 8 ALKENES AND ALKYNES II: Addition Reactions • The oxidation and hydrolysis steps take place with retention of configuration at the carbon initially bearing boron and ultimately bearing the hydroxyl group.
eBook - PDF- James Morrison(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
Such a stereochemically biased addition of a boron-hydrogen bond to the carbon-carbon double bond using chiral alkylboranes is called asymmetric hydroboration. In asymmetric hydroboration the asymmetry is created upon conver-sion of a trigonal carbon of an olefinic double bond to a tetrahedron one. Approach of the chiral hydroborating agent is possible from the two enan-tiotopic faces of the prochiral alkene to form two diastereomeric transi-tion states. The diastereomeric transition state having minimum steric interactions is preferred, leading to the formation of two diastereomers in unequal amounts. The diastereomeric intermediate organoboranes are then transformed into a mixture of two enantiomers in unequal amounts. The efficiency of asymmetric hydroboration apparently depends on two factors: (a) the difference between the steric interactions of the two dia-stereomeric transition states and (b) the reactivity of the chiral hydroborat-ing agent with the alkene. Large differences in steric interactions may increase the efficiency of chiral hydroboration. However, major steric interactions may also result in major decreases in reactivity. Asymmetric hydroboration, discovered in 1961 (Brown and Zweifel, 1961a), marked the beginning of a practical, nonenzymatic asymmetric synthesis. Before that time, asymmetric syntheses had been very ineffi-cient; the excess of one enantiomer over the other was generally quite small and hardly of practical utility. However, more recently the situation has changed dramatically. Several convenient, highly efficient asymmet-ric syntheses have been reported since the early 1970s. Nevertheless, asymmetric hydroboration has remained a valuable procedure for prepar-ing chiral products. Diisopinocampheylborane (Brown and Zweifel, 1961a) achieves almost complete asymmetric induction in the case of c/s-alkenes.
eBook - PDF- John M. McIntosh(Author)
- 2018(Publication Date)
- De Gruyter(Publisher)
We will look at some of these under special headings. 5.10.1 Hydroboration C C BH 3 C C H B organoborane Fig. 5.12 The molecule borane (BH 3 ) undergoes addition to the double bond of alkenes. De-pending on the structure of the particular alkene used, one, two, or all three hydrogens may react with one, two, or three alkene molecules (i.e., the stoichiometry maybe 1:1, 1:2, or 1:3). The product of this reaction is called an organoborane (Fig. 5.12). This reac-tion does not fit the mechanism discussed in Sect. 5.3 since it is found that cis addition is always favored. Furthermore, in molecules with different degrees of substitution on the ends of the double bond, the boron atom becomes attached to the less-substituted carbon. (Contrast this with the addition of HBr.) For examples, see Fig. 5.13. Organoboranes are frequently pyrophoric materials (that is they ignite sponta-neously on contact with air). For this reason, they are seldom isolated. Rather the re-action mixture that contains them is treated directly with a mixture of hydrogen per-C H CH 2 H 3 C + BH 3 H 3 C C H H CH 2 BH 2 BH 3 CH 3 CH 3 H BH 2 Fig. 5.13 74 | 5 Reactions of Alkanes, Alkenes, and Alkynes H 2 C C H CH 3 CH 3 CHCH 3 OH CH 3 CH 2 CH 2 OH CH 3 CH 3 H OH CH 3 OH Fig. 5.14 oxide and sodium hydroxide. This combination of reagents replaces the boron atom with an OH group: i.e., an alcohol is formed. It has been found that the new OH group is always on the same side of the molecule as the boron atom was. The overall effect of addition of BH 3 followed by reaction with H 2 O 2 / OH − is the addition of water in a cis manner. Furthermore, in unsymmetrically substituted alkenes, the orientation of ad-dition is the reverse of that obtained when acid-catalyzed addition of water is carried out. For examples, see Fig. 5.14. This sequence thus allows the anti-Markownikov(!) addition of the elements of water to a double bond.
eBook - PDF- H. Steinberg, A. L. McCloskey, H. Steinberg, A. L. McCloskey(Authors)
- 2013(Publication Date)
- Pergamon(Publisher)
Rearrangement will also occur, but rather more slowly, in 3-coordinate organoboron peroxides. Relatively little work has yet been reported on the homolysis of the O—O bond, but it appears that both of the above heterolytic reactions may occur side by side with a reaction generating free radicals. A. The Reaction of Hydroperoxides with Organoboranes In 1930, Ainley and Challenger (4) showed that dihydroxyphenylborane reacted with hydrogen peroxide to give phenol and boric acid. Reactions of this type have been investigated kinetically by Kuivila and his coworkers. They conclude that the reaction proceeds through the formation of a 4-co-ordinate intermediate (XVIII) which is formed rapidly and reversibly, and which breaks down relatively slowly by a nucleophilic 1,2-rearrangement of the aryl group from boron to oxygen (equation (29) ) (47) . This basic mechanism C e H 5 B(OH) 2 + HOOH C e H 5 OH + (HO) 3 B (0 fast H + + (iii) fast C 6 H 5 -l-v p HO—B—O—OH I HO (ii) slow (XVIII) (29) H 2 0 + HO—B—OC e H 6 HO ORGANOPEROXYBORANES 281 is supported by the fact that dihydroxyphenylborane-O 18 is oxidized by hydrogen peroxide in water-O 18 to give isotopically normal phenol, proving that it derives its oxygen solely from the peroxide group (27) . The detailed characteristics of the breakdown of (XVIII) depend on the conditions. The reaction shows first-order dependence on [HO -] at pH ca. 5, is pH-independent at pH ca. 1 (47) , and is acid-catalyzed under strongly acid conditions when it shows different characteristics with perchloric, sul-furic, and phosphoric acids (48) . The base-catalyzed reaction is accompanied by a component of the same stoichiometry but which shows first order dependence on hydrogen peroxide and second order dependence on the borane.
eBook - PDF- L. Fensterbank, C. Ollivier, L. Fensterbank, C. Ollivier(Authors)
- 2021(Publication Date)
- Thieme(Publisher)
The homolytic substitution at the boron of an alkylboron residue by the aryloxyl radical takes place rapidly to afford a borinic ester (equation 3). These esters are also thought to be ca-pable of hydrogen-atom transfer to alkyl radicals or to the semiquinone radical (equation 4). The resulting aryloxyl radicals could undergo intramolecular homolytic substitution to liberate a second alkyl radical and the B -alkylcatecholborane (equation 5) which can be efficiently reduced as previously demonstrated (Table 4). Following this mechanism, the three alkyl groups can be efficiently reduced. Under normal reaction conditions, bori-nates do not undergo nucleohomolytic substitution. The key step for the success of this 446 Free Radicals 1.11 Generation of Radicals from Organoboranes process is the intramolecular nature of homolytic substitution at the borinate level de-picted in equation 5. Scheme 13 Mechanism of the Protodeboronation of Trialkylboranes [65] R 1 3 B OH OH OH O initiation R 1 R 1 + + OH O + R 1 3 B OH OBR 1 2 + R 1 O OBR 1 2 O B O R 1 + R 1 OH OBR 1 2 + R 1 O OBR 1 2 + R 1 H R 1 H (1) (2) (3) (4) (5) 4-Benzoyl-3a-hydroxy-6a-methyl-5-propylhexahydropentalen-1(2 H )-one ( 21 , R 1 = Pr; n = m = 1); Typical Procedure: [51] Under N 2 , B -propylcatecholborane ( 19 , R 1 = Pr; 0.9 mL, 5.6 mmol) and DMF (0.17 mL, 2.1 mmol) were added to a soln of 2-methyl-2-(4-oxo-4-phenyl-but-2-enyl)cyclopentane-1,3-dione ( 18 , n = m = 1; 359 mg, 1.4 mmol) in 1,4-dioxane (0.35 M). The mixture was heat-ed at 50 8 C and anhyd O 2 (g) oxygen (dried over CaCl 2 ) was slowly bubbled into the soln. The reaction took up to 7 h to go to completion. The mixture was then concentrated and the crude product was purified by flash chromatography (silica gel, cyclohexane/ t -BuOMe); yield: 58%.
eBook - PDFOrganic Chemistry
A Mechanistic Approach
- Penny Chaloner(Author)
- 2014(Publication Date)
- CRC Press(Publisher)
604 14.1 Introduction and Review (c) OH HgO, H 2 O, H 2 SO 4 O O OH CH 3 (CH 2 ) 5 CH 2 OH CH 3 (CH 2 ) 5 C HO CrO 3 , py, CH 2 Cl 2 , 25 °C HO K 2 [Cr 2 O 7 ], H 2 SO 4 , H 2 O, Et 2 O O FIGURE 14.1 Chromium(VI).oxidation.of.primary.and.secondary.alcohols. C 6 H 13 C 6 H 13 Sia 2 BH HOO – , 70 % H BR 2 H Et Et 9-BBN Et R 2 B H Et HOO – O H 2 O, H 2 SO 4 , HgSO 4 OH O C 6 H 13 CH 2 CHO FIGURE 14.2 Carbonyl.compounds.synthesized.by.addition.of.water.to.alkynes.(Sia 2 BH.is.disiamyl- borane,.IUPAC.name.bis.(1,2-dimethylpropyl)borane..9-BBN.is.9-borabicyclo[3.3.1]nonane). (1) O 3 (2) Me 2 S CHO O FIGURE 14.3 Carbonyl.compounds.synthesized.by.ozonolysis. Ac 2 O, AlCl 3 , CS 2 O FIGURE 14.4 Friedel–Crafts.acylation.of.arenes.to.give.aryl.ketones. Chapter 14 – Addition to Carbon–Heteroatom Double Bonds 605 Solutions to Problem 14.1 (a) Although there is none of the usual mercury catalyst here, and we have no real idea (yet) what the diammonium salt is doing, the basic idea of this reaction is straightforward. The alkyne has been hydrated in a Markovnikov addition and then tautomerizes to the ketone: F F F F H + F F + H H H 2 O : F F O + H H F F O H H + O (b) This reaction has two steps—the first is anti-Markovnikov hydration of the double bond, and then the alcohol is oxidized using chromium(VI): Ph Ph O H BH 2 Ph H BH 2 Ph 2 Ph H BR 2 HOO – Ph H B – R 2 O OH Ph H OBR 2 HOO – Ph H O) 3 B H 2 O Ph H OH Cr O O O H + Ph H O Cr O O OH H H 2 O: : 606 14.1 Introduction and Review (c) It’s reasonably easy here to follow which atom has arrived where, and there is a reaction that we should readily recognize the hydration of an alkyne to give a ketone: OH OH H + H 2 O: OH + OH OH OH HO + H OH OH O H H + OH OH O The ring closure step clearly takes place in the acid conditions. We know that protonation of tertiary alcohols followed by water loss is relatively easy, and this gives us a carbocation, ideal for cyclization.
eBook - PDF- Kenneth D. Karlin(Author)
- 2009(Publication Date)
- Wiley-Interscience(Publisher)
For HB(OH)? additions effected by 16-electron intermediates, com- putations favor B-H oxidative addition, alkene insertion into the Rh-B bond. and C-H reductive elimination to generate alkylboronate ester (103). In the latter study. the barrier for a pathway involving a-bond metathesis was only 1.5 kcal/mol ’ higher than the oxidative addition pathway. While addition of HB(0H)z is more relevant to catalyzed addition of HBCat, path- 548 MILTON R. SMITH, 111 Ar 7- L , Rh , 9Y H BCat /H L m , BCat HBCat Scheme 31 L = PPh3 ways involving 14-electron intermediates have not been considered. Given the importance of these intermediates in hydrogenation reactions, reactivity of these species with relevant heteroatom boranes should be considered. Considerable effort has been expended in attempts to harness the high cat- alytic activity of Rh systems for chemoselective and enantioselective cataly- sis. Chemoselectivities have been improved through rational catalyst design and empirical optimization (1 20). For Rh-catalyzed reactions, the reaction pathway As highly system dependent. In addition to hydroboration chem- istry, dehydrogenative boration can be optimized in some cases (121, 122). Unlike Pd-catalyzed dehydrogenative boration of alkenes by B ~ H v (123). dehydrogenative products are only observed for styrene substrates in Rh systems. Other Rh catalysts offer novel regioselectivities for hydroboration of styrene substrates as B-C bond formation at the /3 carbon is generally observed (Scheme 31) (115, 124). In Rh systems, ?r-ally1 intermediates are well documented, and their intermediacy conveniently explains the observed regiochemistry. Formation of secondary products is significant since the chi- ral boronate esters can be synthesized in high enantiomeric purity when chi- ral catalysts are employed (124). This regioselectivity appears to be limited to styrene substrates in late metal systems.
- Steven Nolan, Catherine Cazin, Steven Nolan, Catherine Cazin(Authors)
- 2017(Publication Date)
- Thieme Chemistry(Publisher)
[54] In this transforma- tion, the carbon dioxide synthon serves as the electrophilic carbon partner. A series of Æ,â-unsaturated â-borolactone derivatives 76 can be prepared with high regio- and stereo- selectivity. Interesting from a synthetic point of view is the feasibility of direct â-arylation of the borocarboxylated products by Suzuki–Miyaura coupling. Scheme 32 Borocarboxylation of Alkynes Catalyzed by a Copper–NHC Complex [54] R 2 R 1 B B O O O O + 3 (1.0 equiv) O B O O R 1 R 2 O 76 Li + CuCl(SIMes) (5 mol%) CO 2 (1 atm) LiOt-Bu (1.1 equiv) THF, 80 o C, 14 h R 1 R 2 Yield (%) Ref Ph Ph 81 [54] 4-MeOC 6 H 4 4-MeOC 6 H 4 74 [54] 4-Tol 4-Tol 64 [54] 4-t-BuC 6 H 4 4-t-BuC 6 H 4 77 [54] 4-ClC 6 H 4 4-ClC 6 H 4 68 [54] 4-MeO 2 CC 6 H 4 4-MeO 2 CC 6 H 4 94 [54] 2-thienyl 2-thienyl 94 [54] Me Ph 83 [54] Et Ph 76 [54] H Ph 71 [54] 1.4.4 Catalytic Boron Addition Reactions 349 for references see p 358 In a parallel approach to the open-air hydroborative method described in Scheme 14 (Sec- tion 1.4.4.2), the alkylboration of a series of unsymmetrically substituted internal alkynes can be conveniently performed. [22] The optimal catalytic system involves copper–NHC complex 13 [CuCl(IMes); (2 mol%], bis(pinacolato)diboron (3; 1.3 equiv), and sodium tert- butoxide (1.1 equiv), and the reaction requires a two-equivalent excess of the alkyl halide to proceed (Scheme 33). Exclusive formation of the single regioisomer 77, bearing the alkyl group at the most substituted, â-position, is observed. The method is also highly compatible with additional functionalities.
- M. Christmann, Z. Huang, J. A. Joule, M. Christmann, Z. Huang, J. A. Joule(Authors)
- 2020(Publication Date)
- Thieme(Publisher)
[61] This represents the first such synthesis of 1,4-enynes 97 using non-functional-ized allyl substrates. Electronic effects have a significant influence on the reaction. When an electron-rich alkyne is used, the reaction proceeds smoothly, but if an elec-tron-poor alkyne is used, the yield is greatly lowered. Although the underlying reaction mechanism is currently not known, a pathway was postulated by the authors (Scheme 24). In the first step, di-tert -butyl peroxide (thermal cracking) produces two O-centered alkoxyl radicals. The formed alkoxyl radicals can se-lectively abstract a hydrogen atom from the allyl position of the alkene substrate to form allyl radical 98 . Comparison of the corresponding bond dissociation energies (BDE) of both the O -H bond in tert -butyl alcohol (444.9 kJ·mol – 1 ), produced when di-tert -butyl peroxide is used, and the allylic C -H bond of propene (368.6 kJ·mol – 1 ), shows that this radical abstraction is exergonic, and hence thermodynamically favored. However, under the reaction conditions, the formed tert -butoxyl radical can decompose into a methyl rad-ical and acetone. The open-shell tert -butoxyl radical species can be reduced with a cop-per(I) catalyst to form an oxidized copper(II) complex 100 . This single-electron transfer reaction should be feasible considering the inherent electrophilicity of the alkoxy radical and the reductive power of the copper catalyst (for reference: E 1/2 Cu(II)/CuI in water is – 0.093 V vs. SCE). Taking into account the known propensity of copper(II) complexes to re-act with organic radicals, the formation of the transient copper(III) intermediate 101 can be expected. At the same time, due to the inherent acidity of the protons of the alkyne substrate, it is expected that an organic cuprate 102 will form under the reaction condi-tions.
eBook - PDF- T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
- 2022(Publication Date)
- Wiley(Publisher)
• Both additions are regioselective and follow Markovnikov’s rule: C C C C H X H X X H Haloalkene gem-Dihalide HX HX C C 8.18 Addition of Hydrogen Halides to Alkynes PRACTICE PROBLEM 8.23 Alkenes are more reactive than alkynes toward addition of electrophilic reagents (i.e., Br 2 , Cl 2 , or HCl). Yet when alkynes are treated with one molar equivalent of these same electrophilic reagents, it is easy to stop the addition at the “alkene stage.” This appears to be a paradox and yet it is not. Explain. 8.19 Oxidative Cleavage of Alkynes 383 The hydrogen atom of the hydrogen halide becomes attached to the carbon atom that has the greater number of hydrogen atoms. 1-Hexyne, for example, reacts slowly with one molar equivalent of hydrogen bromide to yield 2-bromo-1-hexene and with two molar equivalents to yield 2,2-dibromohexane: 2,2-Dibromohexane 2-Bromo-1-hexene HBr HBr Br Br Br The addition of HBr to an alkyne can be facilitated by using acetyl bromide (CH 3 COBr) and alumina instead of aqueous HBr. Acetyl bromide acts as an HBr precursor by reacting with the alumina to generate HBr. For example, 1-heptyne can be converted to 2-bromo-1-heptene in good yield using this method: Br (82%) ‘‘HBr’’ CH 3 COBr/alumina CH 2 Cl 2 Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture. These reactions take place through a free-radical mecha- nism (Section 10.10): H Br HBr peroxides (74%) 8.19 Oxidative Cleavage of Alkynes Treating alkynes with ozone followed by acetic acid, or with basic potassium permanganate followed by acid, leads to cleavage at the carbon–carbon triple bond. The products are carbox- ylic acids: R—C C—R′ RCO 2 H + R′CO 2 H R—C C—R′ RCO 2 H + R′CO 2 H Three alkynes, X, Y, and Z, each have the formula C 6 H 10 . When allowed to react with excess hydrogen in the presence of a platinum catalyst each alkyne yields only hexane as a product.
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