Dimerization, oxidative reagents

Using a different dimerization method, namely phenolic oxidation, chiral substrates react in a more stereoselective manner than under reductive conditions. The choice of oxidizing reagent may drastically affect the stereochemical outcome of the reaction. Thus, when potassium hexacyanoferrate(III) is used (17 )-l,2,3,4-tetrahydro-6-methoxy-l,2-dimethyl-7-isoquino-linol couples to give a mixture of atropisomers 3 in 38 % yield and with a d.r. (M)I(P) of 45 553,4. Only one single atropisomer, namely (A/)-3, is formed, in a 66% yield by anodic oxidation, which is attributed to electrode surface effects3. 

Scheme 6.15 Synthesis of precatenane 56 by carbonate-templated oxidative dimerization [64]. Reagents and conditions (a) KOH, EtOH, THF (b) CuCl, CuCl2, py, rt. 

The oxidative dimerization of a,o -dithiols carried out by a large number of oxidizing reagents is a well-known and widely used method for the synthesis of cyclic disulfides. An alternative one-step conversion of the acyclic bisthio-cyanates 297 using TBAF in dry THF at room temperature to form cyclic disulfides in moderate yields, including a limited number of 1,2-dithiolanes 298 (Scheme 54), has been developed <1999TL6489>. The available mechanistic information indicates that the process, induced by so-far-unreported nucleophilic attack by fluoride, tolerates ester and ketal groups, while silyl ethers are cleaved. 

Note that catechols (1,2-dihyroxybenzenes) are readily oxidized to o-quinones, l5 but the products are often sensitive to the electrophilic or nucleophilic species in the reaction medium. Catechol itself gives 125. Dimerization is as much a problem with catechols as with monophenols (see Table 3.4). The conversion of catechol to 125 used silver carbonate and it is noted that silver salts are the classical oxidation reagent for such transformations. Other reagent have been used to oxidize catechol derivatives, including ceric sulfate, lead tetraacetate, DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone), iodate, and periodate. ... 

Osuka and coworkers prepared diporphyrins with direct meso-meso links by oxidation of 5,10,15-trisubstituted porphyrins using AgPFe or AgPp6/l2 as the chemical oxidant (Fig. 20a) [148]. Afterward, several reports also addressed the synthesis of such meso-meso-linked dimers using other oxidizing reagents... 

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

With two equivalents of an organomagnesium hahde, a Gtignard reagent is formed, capable of use in further syntheses (35,36). Cuprous salts cataly2e oxidative dimerization of propargyl alcohol to 2,4-hexadiyne-l,6-diol [3031-68-3] (37). 

The oxidative dimerization of the anion of methyl phenyl sulfone (from a Grignard reagent) in ethereal solution in the presence of cupric chloride in 5% yield has been reported47. Despite the reported48 poor stability of the a-sulfonyl C-centered radicals, Julia and coworkers49 provoked the dimerization (in 13 to 56% yields) of the lithiated carbanion of alkyl phenyl sulfones using cupric salts as oxidants. The best results are obtained with cupric triflates in THF-isobutyronitrile medium (56% yield for R = H). For allyl phenyl sulfones the coupling in the 3-3 mode is predominant. 

Lithium dialkylcopper reagents can be oxidized to symmetrical dimers by O2 at -78°C in THF. The reaction is successful for R = primary and secondary alkyl, vinylic, or aryl. Other oxidizing agents (e.g., nitrobenzene) can be used instead of O2. Vinylic copper reagents dimerize on treatment with oxygen, or simply on standing at 0°C for several days or at 25°C for several hours, to yield LS-dienes." ... 

The general reluctance of reagents to reduce O2 in one-equivalent states is further exemplified in the cases of V(II) and Cr(II). Autoxidation of V(1I), ultimately to V(III), produces ° an intermediate dimer, VOV ", identified spectrally and a known product of the reaction between V(II) and Clearly one path involves an initial two-equivalent oxidation of V(ri) to V(IV) and Swinehart ° calculates that 60 % of the oxidation follows this route. Cr(Il) perchlorate produces a species containing two Cr(III) species linked by one 0x0-or two hydroxo-bridges and Cr(lV) is proposed as the first intermediate F... 

Ketones are oxidatively cleaved by Cr(VI) or Mn(VII) reagents. The reaction is sometimes of utility in the synthesis of difunctional molecules by ring cleavage. The mechanism for both reagents is believed to involve an enol intermediate.206 A study involving both kinetic data and quantitative product studies has permitted a fairly complete description of the Cr(VI) oxidation of benzyl phenyl ketone.207 The products include both oxidative-cleavage products and benzil, 7, which results from oxidation a to the carbonyl. In addition, the dimeric product 8, which is suggestive of radical intermediates, is formed under some conditions. 

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