Pyridinium dichromate allylic oxidation

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

Fluoro-oct-1-en-3-one (82) has been synthesized by allylic hydroxylation of vinyl fluoride (Scheme 31) [77,78], Oxidation of vinyl fluoride (83) using 0.5 equiv. of Se02 and 2 equiv. of ferf-butyl hydroperoxide with a catalytic amount of acetic acid followed by elimination formed to 2-fluoroalk-1-en-3-ols (84) in 32% overall yield for three steps. Subsequent pyridinium dichromate-oxidation of 84 yielded 2-fluoro-oct-1-en-3-one (83) in 81% (Scheme 31). 

Chromium-based oxidants tend to react quicker with unsaturated alcohols, although the difference of oxidation speed with saturated alcohols is normally not sufficient for synthetic purposes. Nevertheless, the chromium-based reagent pyridinium dichromate (PDC) possesses a mildness and, therefore, a relative greater selectivity that allows its occasional employment for selective oxidations of allylic and benzylic alcohols.134... 

Fused 2//-pyran-2-ones are formed in excellent yields and under mild conditions through a Ni-catalysed [2+2+2] cycloaddition of diynes and C02 <02JA15188>. Oxidative demetalation of 0i3-allyl)Mo complexes of pyran with pyridinium dichromate (PDC) introduces a carbonyl function at the allylic terminus offering access to dihydropyranones of high enantiopurity <02JOC5773>. 

Oxidation of alcohols. In the presence of catalytic amounts of pyridinium dichromate, this peroxide can oxidize primary and secondary alcohols to the corresponding carbonyl compounds in 70-100% yield. Reactions catalyzed by dichloro-tris(triphenylphosphinc)ruthenium are useful for highly selective oxidation of primary allylic and benzylic alcohols m the presence of secondary ones. 

The other Corey reagent, pyridinium dichromate (PDC), (C5H5NH )2Cr207 , dissolved in dimethylformamide (DMF) will oxidize allylic alcohols to a,)3-unsaturated aldehydes without oxidizing the aldehyde to the carboxylic acid. ... 

Pyridinium dichromate, prepared from chromium trioxide in a minimum amount of water and pyridine, forms a bright-orange solid and is soluble in water, dimethylformamide, dimethyl sulfoxide, and dimethyl-acetamide sparingly soluble in dichloromethane, chloroform, and acetone and almost insoluble in hexane, toluene, ether, and ethyl acetate. Allylic secondary alcohols are oxidized more rapidly than their saturated analogues. Oxidations are carried out in dichloromethane solutions at 25 °C, and ketones are obtained in high yields (equation 251) [603. ... 

Cyclohexadienones with a wide variety of alkyl substituents at C4 are readily available by alkali metal in ammonia reduction-alkylations" of methyl 2-methoxybenzoate to give cyclohexa-1,4-dienes followed by bis-allylic oxidation by pyridinium dichromate and /ert-butyl hydroperoxide. ... 

The avermectins also possess a number of allylic positions that are susceptible to oxidative modification. In particular the 8a-methylene group, which is both allylic and alpha to an ether oxygen, is susceptible to radical oxidation. The primary product is the 8a-hydroperoxide, which has been isolated occasionally as an impurity of an avermectin B1 reaction (such as the catalytic hydrogenation of avermectin B with Wilkinson s rhodium chloride-triphenylphosphine catalyst to obtain ivermectin). An 8a-hydroxy derivative can also be detected occasionally as a metabolite (42) or as an impurity arising presumably by air oxidation. An 8a-oxo-derivative can be obtained by oxidizing 5-O-protected avermectins with pyridinium dichromate (43). This also can arise by treating the 8a-hydroperoxide with base. 

The silylated methyl ester was then a-methylated with lithium diisopropylamide and methyl iodide in tetrahydrofuran. Reduction of methyl 10-( erl-butyldimethylsilyloxy)-2-methyldecanoate with DIBAL in ether at -78°C afforded the corresponding aldehyde. The 10- tert-butyldimethylsilyloxy)-2-methyldecanal was subsequently coupled in a Wittig reaction with 1-hexyltriphenylphosphonium bromide and n-butyllithium affording (Z)- and ( )-1 -(teri-butyldimethylsilyloxy)-9-methyl-10-hexadecene in a 9 1 ratio, respectively. Deprotection with tetrabutylammonium fluroride (TBAF) in tetrahydrofuran and final oxidation with pyridinium dichromate (PDC) in dimethylformamide resulted in a 9 1 mixture of (Z)- and ( )-9-methyl-10-hexadecenoic acid as shown in Fig. (7). As was also the case with acid 6, the stereochemistry at C-9 in 7 is not known. The key step in the synthesis of the allylic methyl group was a-methylation of a methyl ester, followed by reduction to the corresponding aldehyde, which was used in the subsequent Wittig reaction. 

The efficiency of this oxidation was also evaluated by comparison to other oxidations, such as the Dess-Martin, pyridinium dichromate and Swern oxidations. It was demonstrated that the hypervalent iodine(V)-catalyzed oxidation could be applied for almost all types of fluorinated alcohols and it was comparable to Dess-Martin oxidation, while pyridinium dichromate and Swern oxidations could not be employed for allylic and propargylic alcohols as well as the alcohols having an aliphatic side chain. Additionally, the hypervalent iodine-catalyzed oxidation could be applied for a larger scale reaction (Scheme 4.49) without any decrease in reaction efficiency [81]. 

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