Deoxygenation of the Carbonyl Group

Examine the structure of the actual enamine product One hydrogen is missing from the carbon adjacent to the one bearing the nitrogen (the a-carbon). This hydrogen can be lost as a proton from the iminium intermediate, giving the final product. 

Write the product, in addition to the mechanism of its formation, for the following acid-catalyzed reaction. 

Write the products of reactions (a) and (b) and explain the outcome of reaction (c), all occurring under acid-catalyzed conditions. 

In Summary Primary amines attack aldehydes and ketones to form imines by condensation. Hydroxylamine gives oximes, hydrazines lead to hydrazones, and semicarbazide results in semicarbazones. Secondary amines react with aldehydes and ketones to give enamines. 

In Section 17-5 we reviewed methods by which carbonyl compounds can be reduced to alcohols. Reduction of the C=0 group to CH2 (deoxygenation) also is possible. Two ways in which this may be achieved are Clemmensen reduction (Section 16-5) and thioacetal formation followed by desulfurization (Section 17-8). This section presents a third method for deoxygenation—the Wolff-Kishner reduction. 

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Several other procedures are available for the deoxygenation of the carbonyl groups of aldehydes and ketones to the corresponding methyl and methylene groups, respectively, as outlined below. 

Deoxygenation of the carbonyl group of aldehydes and ketones via the intermediacy of their hydrazone derivatives, known as the Wolff-Kishner reduction,offers an alternative to the thioacetal desulfurization method. The Wolff-Kishner reduction in the presence of hydrazine and NaOH (or KOH) has been replaced largely by the Huang-Minlon method,where the deoxygenation is carried out with hydrazine in refluxing ethylene glycol. 

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

A milder approach for the deoxygenation of aldehydes and ketones involves treatment of the preformed hydrazone with t-BuO K in DMSO at room temperature. Alternatively, conversion of the carbonyl group of aldehydes and ketones into the corresponding tosylhydrazone and reduction of these with NaBH3CN ° or with (RC02)2BH produces the desired methylene compounds in good yields. 

In an early publication [16] the carbonylation of nitroaromatics was described as a stepwise deoxygenation of the nitro group, generating an excited singlet nitrene (probably stabilized by coordination on a metal center). Based on this description, the formation of a metal-imido intermediate was usually assumed in most of the proposed mechanisms until the mid-1980s [5, 34-38]. 

At 120 °C and 1 atm, AH =18 Kcal mol and AS = -30 cal mol K have been calculated [112]. In nonpolar solvents such as decane the reaction does not proceed. The deoxygenation of the nitro group to nitroso is considered to be the rate determining step of the reaction, since the subsequent carbonylation of the nitroso compounds to give the isocyanate derivative is about ten times faster than the one of the nitro compound in the presence of [Rh(CO)2Cl]2 as catalyst [114, 115], a reaction which is accelerated by M0CI5. The mechanism of this reactions is discussed in more detail in Chapter 6 we mention here that side-on rhodium nitrosoarene complexes were proposed as intermediates. However, which really are the coordination modes of the nitrosoarene to rhodium(I) in this system is still a question to be solved. As a matter of fact, the known arylnitroso complexes of mononuclear rhodium(I) complexes have a nitrogen-o-bonded nitroso group [116], and some of them can catalyse the carbonylation of nitrosobenzene to PhNCO[117]. 

The authors have suggested the intermediate formation of a nitrene species by deoxygenation of the nitro group by carbon monoxide. An wtra-molecular methatesis-like reaction of the nitrene complex with the carbonyl group of the amide should yield the corresponding quinazolinone and a transition metal oxo complex (Scheme 19) ... 

Disproportionation complexes are formed by thermal reaction of either trialkyl or triarylphosphine oxides with Fe(CO)s in polar or nonpolar solvents (H. Alper and E. C. H. Keung, unpublished). Irradiation of PhaPO and Fe(CO)5 at 80° gave similar products (Hieber and Lipp, 1959). Treatment of phosphineimines with Fe(CO)5 in THF results in a unique deoxygenation of a carbonyl group of the metal carbonyl to give PI13PO and isonitrile complexes (Alper and Partis, 1972). 

In a study of the deoxygenation of carbonyl compounds by atomic carbon, Dewar and coworkers (8UA2802) presented experimental and theoretical evidence that the carbonyl group can react with carbon atoms to form a carbenaoxirane. 

Reduction to Alkanes. Carbonyl groups can be reductively deoxygenated to methylene functions if both of the two steps represented by Eqs. 1 and 2 proceed to completion. With aldehydes, this process leads to the transformation of the CHO group into a CH3 group. 

The transformation of L-arabinose (58) to lactone 57 was based on a route developed by Marquez and Sharma [51] Selective protection of the primary hydroxy group with TBDPSCl and oxidation of the lactol moiety with bromine afforded lactone 59. Subsequent selective deoxygenation a to the carbonyl group proceeded under Barton-McCombie conditions providing lactone 57 in 21% yield (Scheme 14). 

The Tafel rearrangement only occurs in acid medium. Simultaneous reduction of both carbonyl groups leads to interaction and formation of a cyclopropane. Acid catalysed cyclopropane ring opening follows to yield an a-diketone 28 which undergoes the electrochemical Clemmensen reduction step to the hydrocarbon. Side products include the two monoketones derived by partial deoxygenation of the a-diketone and the secondary alcohols from reduction of these raonoketones. Separate experiments show that the a-diketone 28 can be reduced to the hydrocarbon. 

When the trifluoromethylation occurs on aketonic carbonyl (such as position 2 or 3 in furanose series), it must be followed by a Barton-McCombie deoxygenation of the hydroxyl. It thus leads to the 2- or 3-C-trifluoromethyl deoxyfuranoses. The transformation of these latter compounds into deoxynucleosides has been reported. Trifluoromethyl 2, 3 -dideoxynucleosides and A-2 3 -vinylic nucleosides have also been prepared according to this approach (Figure 6.34). The CF3 group protects the glycosyl base bound from proteolysis in acidic medium, especially in the case of A-2 3 compounds. ... 

This reductive coupling involves two steps. The coupling is induced by single electron transfer to the carbonyl groups from alkali metal, followed by deoxygenation of the 1,2-diol with low-valent titanium to yield the alkene. 

Reduction of aldehydes and ketones usually occurs by the addition of hydrogen across the carbon-oxygen double bond to yield alcohols, but reductive conversion of a carbonyl group to a methylene group requires complete removal of the oxygen, and is called deoxygenation. 

The inter- and intramolecular coupling of two carbonyl groups of aldehydes or ketones in the presence of a low-valent titanium species produces a C-C bond with two adjacent stereocenters, a 1,2-diol (a pinacol). These may be further elaborated into ketones by the pinacol rearrangement or be deoxygenated to alkenes (McMurry reaction). 

In the laboratory of V. Singh a novel and efficient stereospecific synthesis of the marine natural product capnellene from p-cresol was developed. After rapidly assembling the desired carbon framework, it was necessary to remove the carbonyl group from the tricyclic intermediate which was accomplished using Barton s deoxygenation procedure. 

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