Alcohols oxidation with pyridinium chlorochromate

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

A novel one-pot tandem oxidation-cyclization-oxidation process was successfully applied in the transformation of unsaturated alcohols 250 [Eq. (5.315)].860 The intermediate aldehyde formed by oxidation with pyridinium chlorochromate (PCC) undergoes a carbonyl-ene cyclization followed by an additional oxidation to form 3-substituted piperidinones. 

The secondary alcohol is readily oxidized with pyridinium chlorochromate (PCC)25 (65) which is commercially available or easily prepared by addition of pyridine to a solution of chromium(VI)-oxide in hydrochloric acid. 

The reducing power of diborane has been blunted by forming its adduct with dimethyl sulfide. This adduct, Me2S BH3, is stable and commercially available and therefore more attractive as a hydride reagent than diborane itselfNevertheless, the adduct still reduces carboxylic acids to alcohols which are isolated as cyclic boroxins (2 Scheme 1). In a one-pot reaction, carboxylic acids can be reduced to boroxins and then oxidized with pyridinium chlorochromate to the required aldehyde (Scheme I)."... 

The first total syntheses of two skyrins were presented by Nicolaou et al. in 2005 (554). For both, the same route was taken, which is shown in Scheme 12.6. The starting material was the chiral diester 816, which was MOM-protected and then regioselectively mono-hydrolyzed with porcine liver esterase. Oxidation of the remaining alcohol 817 with pyridinium chlorochromate, following elimination with diazabicyclo[5.4.0]undec-7-ene, gave the cyclohexenone 818 in good yield. The phenol 819 was first TBS-protected, and then the amide 820 was obtained from the acid chloride. With ferf-butyllithium and DMF, the corresponding aldehyde was formed, which was converted into the deprotected nitrile by treatment with TMSCN. 

Aldehydes can be prepared from 1° alcohols by the Swern oxidation (Section 12.4B) and oxidation with pyridinium chlorochromate (CsHsNHCrOsCr, or PCC, Sertion 12.4D) ... 

The alcohol citronellol is a terpene found in rose oil. The product formed when citronellol is oxidized with pyridinium chlorochromate (PCC)... 

The synthesis is simply the reverse of the disconnection process, so alkene 139 is converted to alcohol 140 via oxymercuration-demercuration (Chapter 10, Section 10.4.5), and oxidation with pyridinium chlorochromate (PCC Chapter 17, Section 17.2.3) leads to the requisite ketone. Treatment of the ketone with LDA to form the kinetic enolate (note the kinetic control conditions) is followed by addition of propanal and hydrolysis to give the final target, 138. 

We could not deprotect the sulfonamide in the presence of the alcohol group. It was necessary to oxidize with pyridinium chlorochromate (PCC) first, then deprotect the ketone to give sulfonamide S2-... 

These objectives have spurred research directed toward developing alternative synthetic methods. Take alcohol oxidation, for example. As described in Section 15.9, primary alcohols are converted to aldehydes by oxidation with pyridinium chlorochromate (PCC). 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

After the known intermediate 79 (contaminated with ca. 6 % < /.v isomer) [39] was prepared from Hajos-Parrish ketone [40] 78, the tert-butyl ether was cleaved (quant.) and the ketone protected as the acetal (96 %). The secondary alcohol was oxidized by pyridinium chlorochromate (PCC) to provide ketone 80 in good yield (71 %) and after fractional crystallization afforded material absent of any m-hydrindane (Scheme 10.6). [NOTE All compounds shown in Schemes 10.6 and 10.7 are shown in the ent-configuration, as published]. The oxidation of protected hydrindane 80 under Saegusa-Ito conditions [41, 42] gave enone 81 (82 %), confirmed by X-ray crystallography. 

General Procedure for Oxidation of Alcohols to Aldehydes and Ketones with Pyridinium Chlorochromate (PCC)237... 

Although in principle naturally occurring (—)-galanthamine could have been prepared by an identical sequence of reactions commencing with D-tyrosine, an alternate route to 319, the enantiomer of 314, was developed. Thus, epimeriza-tion of the methyl ester group at C-6 of the A -trifluoroacetamide derived from 315 followed by oxidation of the allylic alcohol with pyridinium chlorochromate furnished 319 in 78% optical purity, albeit in low chemical yield. Since 319 could be converted to (-)-galanthamine (291) by the same sequence of reactions outlined for the transformation of 314 to (+)-galanthamine, its preparation may be considered to represent a formal total synthesis of 291 from L-tyrosine (163). 

Because the reagent is slightly acidic, it cannot be used to oxidize acid-sensitive compounds [605. For easier isolation of the products, the complex may be formed in the presence of alumina. After the reagent is stirred with the alcohol at room temperature for 2 h, the aldehyde is isolated by filtration and evaporation of the filtrate [604. Another solid-support oxidant of pyridinium chlorochromate is prepared by treatment of cross-linked poly(vinylpyridine) with chromium trioxide and hydrochloric acid (equation 212) [612]. 

Not only allylic alcohols but also homoallylic alcohols can be epoxi-dized. A peculiar transannular oxidation takes place when 1-methyl-4-cycloocten-l-ol is treated with the Fieser reagent, [CrOj-(CH3C0>20-CH3C00H], or with pyridinium chlorochromate. Two dia-stereomeric keto oxides are formed in different ratios (equation 281) [535],... 

We protect one hydroxyl terminus of the commercially available 1,8-octane diol 1 by reaction with dihydropyran to give the monoalcohol, 8-tetrahydropyranyloxyoctanol 2. The protected alcohol 2 is oxidized to the aldehyde with pyridinium chlorochromate to give 8-tetrahydropyranyl-oxyoctanal 3. 1-Heptyne 4 is coupled with propargyl bromide 5 in a copper catalyzed reaction to produce the diacetylenic 1,4-decadiyne 6. 

Reaction of the C-0 and O-H Bonds Primary alcohols oxidize to carboxylic acids secondary alcohols oxidize to ketones with chromium trioxide or sodium dichromate. Tertiary alcohols do not oxidize under mild conditions. With pyridinium chlorochromate (PCC) the oxidation of primary alcohols can be stopped at aldehydes. 

A quantitative 1,4-chirality transfer is observed in the construction of the acyclic segment C-l to C-ll 11 of the antibiotic ionophore A-23187 (12, calcimycin)441. Both the wanted and unwanted stereoisomer 9 and 10, obtained from the alcohol 8 by pyridinium chlorochromate oxidation followed by Grignard reaction with vinylmagnesium bromide, can be rearranged by the ester enolate procedure simply by changing the reaction conditions to give the stereoisomer 11 with the correct configuration at C-10. 

Reaction of estrone methyl ether with 2,2-dimethylpropane-l, 3-diol in the presence of a catalytic amount of acid leads to derivative 26-1, in which the ketone at 17 is protected as an acetal (Scheme 3.26). Treatment of this intermediate with pyridinium chlorochromate leads to oxidation of the Cg benzylic carbon atom to a carbonyl group (26-2). Potassium tert-butoxide abstracts a proton from the adjacent methylene at C7 alkylation of the resulting anion with 4-(A, A -dimethyl)butyl iodide gives 26-3 as a mixture of diastereomers. The carbonyl group is next reduced to an alcohol by means of sodium borohydride (26-4). Dehydration of the newly introduced hydroxyl group is arguably facilitated by the adjacent aromatic ring (26-5). Aqueous acid removes the 17-acetal to afford 26-6, which is in essence an equilinin derivative. 

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