C549.M. Williams xidations in ynthetic rganic Chemistry The Moffat and wern xidation eactions The classical Moffat oxidation (see: Pfitzner, K.E.; Moffatt, J.G., J. Am. Chem. oc. 1963, 85, 3027~3028), which employs DCC as the dehydrating reagent for DM that is subsequently utilized for the oxidation of primary and secondary alcohols, has formed the basis for a series of related oxidations using DM. The wern modification is perhaps the most popular (see: uang,.l.; mura, K.; wern, D., J. rg. Chem. 1976, 41, 3329~3331 and uang,.l.; wern, D., J. rg. Chem. 1978, 43, 4537~4538). The mechanism for each is given below: mechanism of the Moffat oxidation: C CF 3 C C Et 3 DM: dimethylsulfide DCU: dicyclohexylurea wern oxidation: C 2 C Et 3 DM: dimethylsulfide These two oxidation reactions are related by the common dimethylsulfoxonium ion intermediate which is formed by the net dehydration of DM; base-induced elimination provides the carbonyl product (aldehyde or ketone) and DM. Additional variations on this theme include the use of DM/TFAA and 3 -pyridine complex. The 3 -pyridine system was first described by Parikh and Doering ( ulfur trioxide in the xidation of Alcohols by Dimethylsulfoxide, Parikh, J..; Doering, W. von E., J. Am. Chem. oc. 1967, 89, 5505~5507). The Corey-Kim xidation eaction The use of C (-chlorosuccinimide) and dimethyl sulfide followed by treatment of the alkoxysulfonium salt provides the corresponding aldehyde or ketone from the respective primary or secondary alcohol. (see: Corey, E.J.; Kim, C.U., J. Am. Chem. oc. 1972, 94, 7886). 2 The Dess-Martin Periodinane xidation 1 2 1 2 1 2 Et 3 DM Dess & Martin described a very useful, stable oxidizing agent for the conversion of primary and secondary alcohols to aldehydes and ketones, respectively (see: J. rg. Chem. 1983, 48, 4155~4156). As shown below, the reagent, commonly referred to as Dess-Martin periodinane (a 12-I-5 hypervalent iodine species) is
conveniently prepared from 2-iodobenzoic acid. It rapidly and efficiently oxidizes alcohols to the corresponding carbonyl derivative. I Kr 3 2 4 I 2 Ac, Ac 2 100 o C I Ac Ac Ac Dess-Martin periodinane I Ac Ac Ac Dess-Martin periodinane I Ac Ac I Ac PDC and PCC Chromium-based oxidants have been extensively utilized for the mild and selective oxidations of alcohols and related substrates. The complex of Cr 3 and pyridine is generically known as the arrett oxidations. PDC (pyridinium dichromate) and PCC (pyridinium chlorochromate) are both easily prepared reagents that are stable to storage and handling. In addition, the Cr 3 -pyridine complex is also a very mild and useful reagent. These are shown below. The general reaction of Cr(VI)-based oxidants is shown below and involves a two-electron oxidation of the substrate and a corresponding two-electron reduction of the Cr(VI) species to a Cr(IV) species. owever, the end-product of these oxidations is actually a Cr(III) species since the Cr(IV) oxidation state is labile and further redox disproportionation events ensue. Cr Cr(VI) fast Cr slow Cr Under conditions that favor hydration of the aldehyde (polar solvents such as DMF), the aldehyde hydrate can undergo further oxidation to the acid. 2 Cr Cr(VI) fast Cr slow Cr(IV) Cr Cr(IV) Cr V I Cr IV Cr VI 2 C 2 C= 2 Cr IV 2 Cr V Cr V 2 C 2 C= 2 Cr III PDC Pyridinium dichromate (see: Corey, E.J.; chmidt, G., Tetrahedron Lett. 1979, 399~402) has proven to be a useful alternative to the Collins reagent since, the reagent is easily prepared from Cr 3 and pyridine in water giving a stable crystalline solid. The reactivity of the oxidant can be modulated by the solvent chosen. PDC as a suspension in C 2 2 is mild and oxidizes primary alcohols to aldehydes. n the other hand, PDC in DMF (soluble) is much more reactive and will oxidize the aldehyde up to the acid. ) 2 Cr 2 7 ) 2 Cr 2 7 DMF 84%
Cr 3 C 2 2 C Collins eagent The Collins reagent is a mild oxidizing agent that can be used effectively for the conversions of primary alcohols to aldehydes. It is neither acidic nor basic. owever, it is inconvenient to prepare and requires a large excess for the reaction to go to completion typically. -Cr 3 - Jones eagent Collins eagent The Jones oxidation reaction consists of adding aqueous chromic acid (Cr 3 in 2 4 ) is added to a solution of the alcohol in acetone (see: owers, A.; alsall, T.G; Jones, E...; Lemin, A.J., J. Chem. oc. 1953, 2548. Cr 3, 2 4 i-pr acetone (added to consume excess Jones reagent) ayer-villiger eaction The ayer-villiger reaction is an excellent method for converting ketones to lactones (and thus, w- hydroxy acids). The more substituted group migrates from the tetrahedral intermediate. peracid m-cpa F 3 CC 3 r r The arton eaction The arton reaction is a radical-based method to remotely functionalize an unactivated C- bond as shown below: Ac Ac 1. C 2. hn 3. 3
The general reaction involves the formation and photochemical rearrangement of a nitroxyl intermediate that tautomerizes to an oxime; hydrolysis affords the corresponding aldehyde of ketone. 1. 2. hn 3. 3 hn - 3 oxime Criegee Glycol eavage below. Vicinal (1,2-) diols can be cleaved with Pb(Ac) 4 to the corresponding di-carbonyl compound as shown 1 3 2 4 Pb(Ac) 4 1 2 3 4 Pb(Ac) 4 Pb(Ac) 4 C C 2 Et Et offman-loffler-freytag eaction The offma-loffler-freytag reaction is related to the arton reaction in that, an unfunctionalized C- bond can be oxidatively activated for the formation of cyclic amines. 2 3 1 C or 2 or t-u 2 3 1 1. hn 2. base 2 1 3 2 1 3 2 1 3 2 3 1
2 Et 2 90% 2 Et t-u 99% Et hn (g lamp) 2 4 2 Et 1. a, p=7 2. (C) 2 K 2 C 3, 2 dioxane 53% Et t-c 1. Li, TF, 2 2. TFA, C 2 2 3. Dowex 50W X-100 90% Pummerer earrangement The Pummerer rearrangement is a net oxidation of an alcohol-bearing carbon atom to the corresponding aldehyde or ketone. 1 2 2 1 Ph [ox] 1 2 Ph 1 Ph TFAA hydrolysis 2 2 1 or Ac 2 Ph 1. TFAA tu t-u 2 C C 2 2. g, CdC 3, TF 2 81% 2 C C 2 The Fenton xidation The Fenton reaction involves the reduction of 2 2 by Fe(II) which generates hydroxyl radical. This is typically a non-selective oxidant since, hydroxyl radical is an extremely reactive oxidant capable of oxidizing non-activated C- bonds. 1 2 2 2, Fe 2 1 2 Fe(III) 2 Fe(II) 2 aber-weiss eaction Fe(II) 2 2 Fe(III) 2 Fenton eaction iley xidation The ene reaction between e 2 and an activated C 2 group gives the corresponding ketone. 1 2 Ac Ac e 2 2 1 1., 2 2. e 2, Et
L-selectride: lithium tri-sec-butylborohydride Li K-selectride: potassium tri-sec-butylborohydride K L-selectride: lithium trisiamylborohydride Li irch eduction ouveault-lanc eduction osenmund eduction tephen eduction Wolff-Kishner eduction educing Agents