Alcohols, alkynic oxidation

In this chapter the first of the two most important categories of oxidations catalysed by Ru complexes (the other being alkene and alkyne oxidations in Chapter 3) are considered. The approach in this and subsequent chapters differs from that of Chapter 1, concentrating here on the substrate rather than on the oxidant. The text is divided into the categories of alcohols and their oxidations. There are summaries in section 2.3.6 of systems of limited apphcability which are mentioned only in Chapter 1, and in section 2.3.7 of large-scale (>1 g) oxidations. 

Heterogeneous oxidations,1 A variety of substrates can be oxidized by this solid reagent in refluxing hexane (1.5 -24 honrs). The reaction proceeds in good yield with alcohols (85-100%), aldehydes (65-80%), and sulfides but alkenes, alkynes, epoxides, and amides arc not oxidized. Surprisingly allylic alcohols arc oxidized more slowly than saturated alcohols. 

A synthesis of the furanoeremophilane ( )-ligularone has been accomplished via the intramolecular Diels-Alder reaction of an oxazole with an alkynic dienophile (81JA4611). The lactone (359) was treated with lithium methylisocyanide to yield the oxazole (360). Oxidation of alcohol to aldehyde and reaction of this unstable aldehyde with lithiopropyne gave a 55 45 mixture of diastereomeric alcohols (361). Oxidation of the mixture gave a single alkynic ketone (362) which when refluxed in ethylbenzene afforded the desired furanosesquiterpene (363 Scheme 78). 

Aldehydes, RCHO (Sec. 7.9) (Sec. 7.9) (Sec. 8.4) (Sec. 17.7, 19.2) (Sec. 19.2, 21.6) from disubstituted alkenes by ozonolysis from 1,2-diols by cleavage with sodium periodate from terminal alkynes by hydroboration followed by oxidation from primary alcohols by oxidation from esters by reduction with DIB AH [HA1(i-Bu)2]... 

Although the reactions between alkynes or alkenes and metal clusters are the main source of alkyne-substituted complexes, there are other reagents which can produce similar products. Two such reagents are tetraphenylcyclopentadienone, which in the reaction with Ru3(CO)i2 produces Ru3(CO)10(PhCCPh) (167), and dimethyl-vinylarsine, which has been made to react with several carbonyl clusters [Eq. (8)] (168, 169). In the reaction of M3(CO)12 (M = Ru, Os) with a number of tertiary phosphines and aromatic alcohols, an oxidative addition takes place and benzyne-triosmium compounds are obtained (170-176). The fact that Os3(CO)uPEt3 can be converted into an alkyne compound (177) suggests that the conversion goes through substituted intermediates. Carbene derivatives of clusters have also... 

HydrosilyUUion. This silane is useful for hydrosilylation of alkencs and alkynes because the C—Si bond of the adducts is oxidized by 30% H,0, in the presence of KF, KHF, or NaHCO, with formation of the corresponding alcohol. The oxidation occurs with retention of configuration at carbon. At least one alkoxy group on silicon is necessary for this oxidation. Hydrosilylation followed by oxidation permits conversion of 1-alkenes to anti-Markownikoff alcohols (equation 1) and of internal alkynes to ketones (equation II). 

Chlorination and oxidation. This reagent is stable and easy to handle. It can be used to introduce chlorine atoms to C-2 of 2-substituted 1,3-dioxolanes, the a-position of aldehydes besides alkenes and alkynes. Oxidation of alcohols such as benzyl alcohol and cyclooctanol in MeCN requires pyridine-DABCO (4 1) as acid scavenger. 

Via tandem alcohol oxidation/alkyne hydration/aldol condensation sequence from benzylic alcohol+alkyne... 

A carbonyl is reduced to an alcohol (Chapter 19) and an alcohol is oxidized to a carbonyl (Chapter 17). The OH unit of an alcohol is converted to an X group, where X is a halide (or a sulfonate ester), by standard means (Chapter 11, Section 11.7) and hydrolysis of a halide or a sulfonate ester gives an alcohol (Chapter 11, Section 11.4). Elimination of a halide leads to an alkene (Chapter 12, Section 12.1) and addition of HX to an alkene gives C-Xmolecrdes (Chapter 10). Addition of two equivalents of a halogen to an alkene, followed by elimination, leads to an alkyne (Chapter 12) reduction of the alkyne gives the alkene again (Chapter 19). 

A tetrahydropyranyl linker is an acid-sensitive linker for alcohols. Nitrile oxides were generated in situ from tetrahydropyranyl-linked nitro alkanes and phenyl isocyanate under Mukaiyama conditions, and reactions with various alkynes gave resin-bound isoxazoles (Scheme 11.39). Cleavage with diluted trifluoroacetic acid gave isoxazoles as primary alcohols in a traceless manner. A library of 3-hydroxymethyl-4,5-disubstituted isoxazoles was prepared in a parallel and automated fashion by a 96-well plate synthesizer with an average yield of 60%. 

When you know what functional group you want to create, you can try to remember the various ways it can be synthesized. For example, a ketone can be synthesized by the acid-catalyzed addition of water to an alkyne, hydroboration-oxidation of an alkyne, oxidation of a secondary alcohol, and ozonolysis of an alkene. Notice that ozonolysis decreases the number of carbons in a molecule. 

The alkylborohydrides thus produced are converted to alcohols on oxidation, and alkenylboranes to alkanes by protonolysis. The hydroboration occurs preferentially in an anti-Markownikoff fashion. In contrast to what occurs with diborane, the Ti catalyzed hydroboration affords almost exclusively monohydroborated products (mixture of isomers) with alkynes or alkadienes, even in the presence of an excess of NaBH4. 

Whilst acetylenic alcohols can be employed directly in Cadiot-Chodkiewicz reactions [9], protection of the alcohol (usefully as the Thp ether) is necessary for Castro coupling [14]. A variation based upon these two processes involves coupling of terminal alkynes with 3-bromopropynol (10) in the presence of pyridine [15]. For primary alcohol products, oxidation to the aldehyde with nickel peroxide followed by base-catalyzed decarbonylation generates the new terminal acetylene e.g. Fig. 1.10. 

When 90 was heated in toluene, the hydroxylamine added to the alkyne to afford nitrone 91 (after tautomerization of a presumed intermediate N-hydroxyenamine) which was trapped by styrene in an intermolecular 1,3-dipolar cycloaddition to provide 92. An oxidation state adjustment (with removal of the chiral auxiliary) gave 93. The TBDPS protecting group was removed and the resulting primary alcohol was oxidized with IBX (94) (related to the Dess-Martin periodinane) to give aldehyde 95. Application of the Yamamoto variation of the Peterson olefmation gave 96 with decent control over olefin geometry. 

As an application of maleate formation, the carbonylation of silylated 3-butyn-l-ol affords the 7-butyrolactone 539[482], Oxidative carbonylation is possible via mercuration of alkynes and subsequent Lransmetallation with Pd(II) under a CO atmosphere. For example, chloromercuration of propargyl alcohol and treatment with PdCF (1 equiv.) under 1 atm of CO in THF produced the /3-chlorobutenolide 540 in 96% yield[483]. Dimethyl phenylinale-ate is obtained by the reaction of phenylacetylene, CO, PdCU, and HgCl2 in MeOH[484,485]. 

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