Alcohols, secondary, conversion into examples

Conversion of saturated, primary alkyl and aryl alkyl alcohols into the corresponding aldehydes can be achieved by this method provided that the alcohols are entirely dissolved in the organic phase. Relatively unstable protective groups are not affected, as in the oxidation of the acetonide of 1,2,6-hexanetriol, whereas conjugated and isolated double bonds give rise to side reactions which considerably decrease selectivities and yields.4 Some examples of aldehydes synthesized with this method are reported in Table 1. Under the same conditions, secondary alcohols are oxidized to ketones. Addition of catalytic amounts of quaternary onium salts allows fast and total conversion of primary alcohols and aldehydes into carboxylic acids making this methodology very versatile 4... 

The Mitsunobu reaction, discovered by Mitsunobu in the late 1960s, has become one of the most widely used reactions in organic chemistry. The reaction has become the standard method for the inversion of secondary alcohols, the conversion of alcohols into amines and sulfides, and many other applications. New uses for this versatile reaction continue to be developed. The Mitsunobu reaction, due to its mild reaction conditions, has found wide application in total synthesis, and heterocyclic and medicinal chemistry. Since the Mitsunobu reaction has been extensively reviewed during the last thirty years, this chapter will focus primarily on applications of the Mitsunobu reaction during the last fifteen years. This review will cover recent examples for the various uses of the Mitsunobu reaction and introduce several new applications of the reaction. Recently developed phosphine and azadicarboxylate reagents will be covered as well. 

For example, the acetate prepared from l,l,l-trifluoro-2-octanol was transformed into (.R)-l,l,l-trifluoro-2-octanol in 96% when hydrolyzed with lipase MY at 40% conversion. Other, trifluoromethylated chiral secondary alcohols shown in Table 2 were prepared by the same procedure. The corresponding alcohols were converted to their acetate, followed by asymmetric hydrolysis to attain the higher enantiomeric excess [28]. 

Imidazolylsulfonates.2 Alcohols can be converted into the imidazolylsulfonates by reaction of the alkoxides (NaH, DMF) with 1. Another route involves conversion to the chlorosulfate (sulfuryl chloride) followed by reaction with 1. The imidazylate group is an efficient leaving group in reactions with nucleophiles. Displacement reactions with even secondary imidazylates can proceed in high yield. Imidazylates are also useful in elimination reactions (second example). 

Subsequently, in 1999 the same group showed that the activity of the ruthenium hydrotalcite was significantly enhanced by the introduction of cobalt(II), in addition to ruthenium(III),in the Brucite layer [115]. For example, cinnamyl alcohol underwent complete conversion in 40 min in toluene at 60 °C, in the presence of ruthenium/cobalt hydrotalcite, compared with 31% conversion under the same conditions with ruthenium hydrotalcite. A secondary aliphatic alcohol, 2-octanol, was smoothly converted into the corresponding ketone but primary aliphatic alcohols, for example, 1-octanol, exhibited extremely low activity. The authors suggested that the introduction of cobalt induced the formation of higher oxidation states of ruthenium, for example, Ru(IV) to Ru( VI), leading to a more active oxidation catalyst. However, on the basis of the reported results it is not possible to rule out low-valent ruthenium species as the active catalyst in a hydridometal pathway. The results obtained in the oxidation of representative alcohols with ruthenium hydrotalcite and ruthe-nium-cobalt-hydrotalcite are compared in Table 5. 

Primary alcohols are oxidized to aldehydes or acids, and secondary alcohols are oxidized to ketones. Tertiary alcohols resist oxidation, unless they are dehydrated in acidic media to alkenes, which are subsequently oxidized. The conversion of alcohols into carbonyl compounds can be achieved by catalytic dehydrogenation or by chemical oxidation. Catalytic dehydrogenation is especially of advantage with primary alcohols, because it prevents overoxidation to carboxylic acids. Examples are tabulated in equations 223-227 and 265-268. 

Radioactive isotopes are commonly used for competitive KIE measurements in a double-label experiment, yielding kn/kj or ko/kj ratios on kcat/ M- This technique typically utilizes tracer-level radioactivity in the position of interest (primary or secondary) to monitor the transfer of radioactivity from reactant to product, and requires a remote label (e.g. C) in order to measure the conversion of unlabelled substrate to product. As an example, [ring- C(U)]benzyl alcohol and [l- H]benzyl alcohol (Scheme 10.2) can be used to simultaneously measure the primary and a-secondary kn/kj effects in the reaction catalyzed by alcohol dehydrogenase (ADH), as the tracer tritium is incorporated randomly into primary and a-secondary positions [6, 10]. 

Pyridinium Chlorochromate. The need for improved oxidation of primary alcohols and greater ease for isolation of products prompted further research into the nature of Cr(VI) reagents. Corey found that addition of pyridine to a solution of chromium trioxide in aqueous HCl allowed crystallization of a solid reagent characterized as 31, pyridinium chlorochromate (PCC). This reagent was superior for the conversion of primary alcohols to aldehydes in dichloromethane but less efficient than the Collins oxidation when applied to allylic alcohols. Oxidation of 1-heptanol with PCC in dichloromethane gave 78% of heptanal, for example. As stated by Corey, PCC is an effective oxidant in dichloromethane although aqueous chlorochromate species are not very effective oxidants. Oxidation of secondary alcohols to ketones is straightforward, as in Banwell s synthesis of y-lycorane, in which 32 was oxidized by PCC to the ketone (33). ... 

This resolution method was found to be appUcable to some cyanohydrins 15 and secondary alcohols 16. Very interestingly, the racemic cyanohydrins were converted into a pure optically active isomer in almost quantitative yield in the presence of 72 For example, when a solution of racemic l-cyano-2,2-dimethy 1-1-phenyl-propanol 15a) (1.0 g, 5.3 mmol) and 72 (2.1 g, 5.3 mmol) in methanol (2 ml) was kept in an uncapped flask for 24 h at room temperature, a brucine inclusion compound of 94% ee of +yi5a was obtained in quantitative yield, which upon decomposition gave 94% ee of - -)-15 a (1.0 g). Repeating inclusion formation of the 94 % ee containing (ri- )-75a (1.0 g) Avith 72(2.1 g) one more time yielded 100 % ee of (+)-15a [1.0 g, [a]jj -1- 15.9° (c 1.0 in MeOH)]. The process of the complete conversion of racemic cyanohydrin to one enantiomer consists of racemization of cyanohydrin through the equilibrium in Equation 1 and selective inclusion of one enantiomer in brucine... 

While DDO has been little used for the oxidation of simple alcohols, it has found application in useful conversions of vicinal diols. The oxidation of tertiary-secondary diols to a-hydroxy ketones occurs without the usual problem of oxidative cleavage between the two functions (eq 16). DDO has also been used to convert appropriate optically active diols selectively into a-hydroxy ketones of high optical purity for example, see (eq 17). ... 

It was mentioned that oxidation by DDO allows the clean conversion of secondary alcohols into carbonyls under mild conditions. In this transformation the dioxiranes rank high with respect to transition-metal oxidants because of their efficiency, superior versatility, and ease of operations. Based on kinetic data and the application of reaction probes, the oxidation proceeds via a substantially concerted O-insertion by the dioxirane into the C-H bond alpha to the OH functionality generating a ge/w-diol C(0H)2, hence the carbonyl. As shown by the example in eq 36, remarkable chemoselectivity is achieved in the oxidation of epoxy alcohols in that the corresponding epoxy ketones are formed in high yield, while the epoxy functionality remains untouched. The epoxy ketone in eq 36 is a key intermediate in the convergent synthesis of active lQ ,25-dihydroxyvitainin D3 analogs. ... 

Based on the ability of the PhI(OAc)2-TEMPO system to selectively oxidize primary alcohols to the corresponding aldehydes in the presence of secondary alcohols, Forsyth and coworkers have developed the selective oxidative conversion of various highly functionalized l°,2°-l,5-diols into the corresponding 8-lactones [155]. A representative example, showing the conversion of substrate 127 into the 8-lactone... 

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