PDC oxidation

Pyridinium dichromate (PDC) may oxidize alcohols all the way to the corresponding carboxylic acids instead of aldehydes and ketones as PCC does. 

Example 2, Cleavage of primary carbon-boron bond  

4 Nakamura, M. Inoue, J. Yamada, T. Bioorg. Med. Chem. Lett. 2000,10,2807-2810. 

Modified one-pot Julia olefinafion to give predominantly ( )-olefins from het-eroarylsulfones and aldehydes. A sulfone reduction step is not required. 

The use of larger counterion (such as K ) and polar solvents (such as DME) favors an open transition state (PT = phenyltetrazolyl)  

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 135, Springer-Verlag Berlin Heidelberg 2009 

Julia-Lythgoe oleflnation. In Name Reactions for Homologations-Part 1 Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2009, pp 447-473. (Review). 

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The approach was carried out on a ketohexo backbone bearing acid-sensitive ketal groups (Scheme 29). l,2 4,5-Di-0-isopropylidene-/ -D-fructo-pyranose readily underwent PDC oxidation of the 3-OH, followed by selective acid-catalyzed hydrolysis of the 4,5-ketal to afford a partially protected ketone in 94% overall yield. For the subsequent HSCN condensation, adapted acidic conditions had to be established to avoid 1,2-isopropylidene cleavage under thermal conditions and the target OZT (R = H) could be isolated in 60% yield. When performed in ethanol, the condensation afforded the acetalic counterpart (R = Et) albeit in lower yield. 

The key step in this synthesis was an oxidative cyclization of the primary alcohol 125 upon PDC oxidation, yielding the lactam 126 (Scheme 31). The... 

CHCHiOH - C—0. The diol 1 can be oxidized by PDC to the dionc 3. A short-term reaction gives the keto alcohol (lactol) 2. This is apparently the first example of PDC oxidation of a primary alcohol beyond the aldehyde stage. Other oxidants based on Cr also oxidize to 3, but in lower yields. The loss of the CH OH group may be a result of facile enolization of the intermediate aldehyde.2... 

Acetic acid,127 pyridinium trifluoroacetate (PTFA)121 or pyridinium tosylate (PPTS)128 are often added in order to speed up PDC oxidations. Acetic acid, which is described as superior127a and very easy to remove, is used most often. Although this precludes the advantages of using an almost neutral PDC medium, it provides a very useful substantial acceleration of the oxidations. The combined employment of molecular sieves and an acid can provide a synergistic accelerating effect.127a... 

Acetic anhydride also provides a substantial acceleration of PDC oxidations, which is particularly useful in sugar and nucleoside chemistry.129... 

A PDC oxidation, followed by removal of the chromium salts with Florisil , gives a good yield of an unstable aldehyde. Attempted oxidation using Swern conditions met the problem of decomposition of the aldehyde during column chromatography. 

TMS and TBS ethers can be cleaved and oxidized to aldehydes or ketones in a one-pot reaction, employing a standard PDC oxidation in which trimethylsilyl chloride is added.138... 

When the formation of the lactone is purposefully looked at, DMF that promotes the oxidation of primary alcohols in carboxylic acids can be used as solvent in PDC oxidations. The resulting hydroxycarboxylic acid would cyclize to a lactone if favoured.173... 

Some examples of further non-oxidative transformations suffered in situ by aldehydes and ketones, obtained by PDC oxidation, are listed bellow. 

In an alternative route,2 Boc-protected amino acids are reduced to the protected amino alcohol with borane-THF (45-95% yield) and pyridinium dichromate is used for oxidation to the aldehyde (75-90% yield). The optical rotations of the aldehydes obtained by these two procedures differ considerably, presumably owing to racemization encountered in the PDC oxidation. 

Peptide mimetics containing the a-ketoamide moiety are very important because they act as cysteine protease inhibitors. In fact, the a-ketoamide residue forms hemithioacetals with the -SH group of the cysteine residue of the enzyme [32], Nakamura et al. [26b] reported the preparation of a 100-member combinatorial library of a-ketoamides by means of a two-step one-pot synthesis. The first step consisted of the Ugi-4CR between (+/— )lactic acid, amines, isocyanides, and aldehydes leading to the formation of the lactamides 40 which were oxidized to the corresponding pyruvamides 41. This one-pot procedure was performed in THF since the PDC oxidation was incompatible with the presence of methanol. Five a-ketoamides showed an 80% average purity (Scheme 2.17). 

Cysteine proteases play key roles in the pathogenesis of a variety of disease states including osteoporosis [49], muscular dystrophy [50] and several CNS-related disorders [51]. A 100-member library of a-ketoamides 50 was generated via a two-step one-pot synthesis, in which the initial condensation was followed by a pyridinium dichromate (PDC) oxidation (Scheme 11.9). Yields were respectable, ranging from 53 to 75%. Note that a-ketoamides are potential reversible inhibitors with the ability to form hemi-thioacetals with the active thiol of cysteine residues. 

Initially, Corey and Schmidt found that by addition of pyridinium trifluoroacetate (0.4 equiv.) to their reactions, there was an increase in rate and the amount of PDC needed for complete oxidation diminished. Subsequently, several other techniques have been devised to improve the rate and efficacy of PDC oxidations (most frequently in the field of carbohydrate research). 

When used in DMF, PDC oxidizes aldehydes and primary alcohols to carboxylic acids. However, allylic primary and secondary alcohols are oxidized only to the a ,j3-unsaturated carbonyl compounds. All these oxidations proceed in high jrield. 

The reaction of a a-phenylselanyl enolate derived from 15-pentadecanolide and fSj-propylene oxide furnished a 1 1 mixture of lactones [50] (Scheme 41). The butyrolactone, resulting from a partial trans lactonization, led to (+)-Squa-mostanal-A in 55 % yield after selenoxide syn elimination and PDC oxidation of the hydroxy group. 

In DMF solution, however, PDC oxidizes nonconjugated primary alcohols to the corresponding carboxylic acids.Oxidations of 2° alcohols by PDC in DMF proceed to give the corresponding ketones. 

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