Collins reagent alcohols

This is followed by hydrolysi.s of the ester moieties with potassium carbonate and reesterification of the carboxy moiety with diazomethane to produce intermediate 65. The solitary free alcoholic hydroxyl at C-9 is oxidized with Collins reagent and the silyl ether groups are removed with acetic acid to give enprostil (63) [15]. 

The Collins reagent in CH2CI2 oxidizes silylated primary alcohols in preference to the more hindered silylated secondary alcohols, as described for oxidation of the prostaglandin intermediate 2963 to the rather labile aldehyde 2964, which is immediately subjected to a Horner-Wittig-reaction to introduce the lower side chain [206] (Scheme 12.61). 

The most widely used chromium(VI)-oxo reagents for synthetic use in organic chemistry are the Collins reagent, Cr03(py)2,273 and the Corey reagent, Cr03CrpyH+,297 with the latter being superior for the oxidation of primary alcohols to aldehydes.275... 

Collins reagent is used for the introduction of carbonyl groups at allylic positions." This transformation of alkenes into enones is much slower than the oxidation of alcohols, requiring a great excess of Cr03 2Py and prolonged reaction times. Consequently, alcohols can be oxidized to aldehydes and ketones by Collins reagent without interference from alkenes. 

Collins reagent can transform tertiary allylic alcohols into rearranged enones,101 similar to PCC, which is routinely used for this purpose (see page 55). As this reaction is normally slower than the oxidation of primary and secondary alcohols, these can be oxidized with Collins reagent with no interference from tertiary allylic alcohols present in the same molecule.102... 

Protecting groups, including very labile ones, withstand the action of Collins reagent. The very labile primary TMS ethers are transformed into the corresponding aldehydes.103 As secondary and tertiary TMS ethers resist the action of Collins reagent, a protocol involving per-silylation followed by Collins oxidation allows the selective oxidation of primary alcohols in the presence of secondary ones.104... 

Most functional groups resist Collins oxidation, including the oxidation-sensitive sulfides106 and thioacetals.103 Although Collins reagent can transform alkenes into enones" and alkynes into inones,107 these reactions are slower than the oxidation of alcohols into aldehydes or ketones. Therefore, alcohols can be usually oxidized with no interference from alkenes108 or alkynes.109... 

Collins reagent is able to transform benzyl ethers into ketones and benzoates.110 Normally, this causes no interference with the oxidation of alcohols, because the oxidation of benzyl ethers demands more drastic conditions. 

Selenides are oxidized to selenoxides that normally suffer an in situ elimination.111 Amines are destroyed,112 although its protection as amides or carbamates prevents the reaction with Collins reagent. Lactols are very quickly oxidized to lactones,113 unless a very great steric hindrance is present.114 Tertiary lactols suffer oxidation via its opened hydroxyketone form.115 The oxidation of tertiary lactols may be slow, so that an alcohol can be selectively oxidized. 

Similar to Jones reagent, Collins reagent can produce a hydroxy directed epoxidation of allylic alcohols. This side-reaction only occurs in a limited number of allylic alcohols, most of them being oxidized uneventfully to the corresponding enones.117... 

Sometimes, alcohols can direct the oxidation of alkenes, resulting in highly stereoselective formation of tetrahydrofurans by the action of Collins reagent. Thus, 1,2-diols can form cyclic chromate esters that can intramole-cularly oxidize alkenes, positioned so as to allow the operation of five-membered cyclic transition states.119... 

Oxidation of a chiral alcohol. The (S -alcohol 1 is oxidized in high yield by DMSO-C5H5N SO3 to the aldehyde 2 with no more than 0.1% racemization. The same oxidation when effected with Collins reagent or with H2CrO4-Si02 (8, 110) proceeds with 5% and 22% racemization, respectively.4... 

Alternatively it is possible to oxidize a primary alcohol no further than to give the aldehyde. This is the domain of the Collins reagent, PCC, PDC, or activated dimethyl sulfoxide. The oxidation of primary alcohols with K2Cr207 in aqueous solution to nothing but the aldehyde, (i.e., without further oxidation to the carboxylic acid) is possible only if a volatile aldehyde results and is distilled off as it is formed. This is the only way to prevent the further oxidation of the aldehyde in the (aqueous) reaction mixture. Selective oxidations of primary alcohols to aldehydes with the Jones reagent succeed only for allylic and benzylic alcohols. Otherwise, the Jones reagent directly converts alcohols into carboxylic acids (see above). 

Many other reagents and procedures have been developed for oxidizing alcohols. Some are simply modifications of the procedures we have seen. For example, the Collins reagent is a complex of chromium trioxide and pyridine, the original version of PCC. The Jones reagent is a milder form of chromic acid a solution of diluted chromic acid in acetone. 

The same intermediate 74 was synthesized by J. W. Bruin et al74 by an alternative route. They reduced the ester function of the pyroglutamate with LiBH4 to the primary alcohol 75a which was protected as the acetate 75b to prevent O-alkylation. Reaction of the sodium salt of 75 b formed with NaH in dimethylformamide, with methyl-7-bromoheptanoate followed by methanolysis of the acetate function gave 74. Oxydation of the alcohol 74 by Pfitzner-Moffat-oxydation or oxydation with Collins reagent led to the unstable aldehyde 77. 

RCHjOH —> RCOOC(CH,),. This transformation can be effected in sugars with the Collins reagent (4 equiv.) in CH.Cb/DMF followed by addition of acetic anhydride (9,121) and a large excess of r-butyl alcohol (equation I). This conversion is probably general except for aromatic aldehydes. 

Table 3 Rearrangement of Tertiaiy Allylic Alcohols with the Collins Reagent...

In a similar fiashion to the Collins reagent, PCC will also induce oxidative rearrangement of tertiary allylic alcohols (Table S). PCC, and several other chromium oxidants, will also cause tertiary cyclopropyl alcohols to rearrange to give 3,y-unsaturated carbonyl compounds (equation 8). ... 

Pyridinium chlorochromate (PCC) Corey and Suggs prepared PCC by mixing CrOs with pyridine in HCl. PCC is used for the oxidation of primary and secondary alcohols in CH2CI2. This reagent is less efficient than Collins reagent for the oxidation of allyl alcohols. 

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