Methyl iodide reductive elimination

Williams carried out a Julia coupling similar to the Keck example. With the removal of the acetal functionality, the coupling step of the Julia reaction was efficient, but the usual reductive elimination procedure failed. As an alternative to the acetylation and reductive elimination procedure, the P-sulfo-nyl xanthate was formed by quenching the addition reaction with carbon disulfide and methyl iodide. Reductive elimination was then carried out with tri-n-butyltin hydride to yield the desired ( )-alkene (399) in an 85 15 ratio with the (Z)-alkene in 83% overall yield (equation 91). 

Scheme 25 Proposed mechanism of the kinetically controlled methyl iodide reductive elimination from Pt(IV). Due to the reversibility of the reductive elimination step, the thermodynamic products of CH3-CH3 coupling are eventually formed as the major species...

The latter complex undergoes CO loss to generate coordinatively unsaturated 4.28. Conversion of 4.28 to 4.30 is the crucial step that is responsible for the formation of the branched isomer. Obviously this reaction is possible only when propylene is present as one of the reactants, or under reaction conditions where propylene from //-propanol is generated in situ. Conversion of 4.28 to 4.30 is an example of alkene insertion into an M-H bond in a Markovnikov manner (see Section 5.2.2 for a discussion on Markovnikov and anti-Markovnikov insertion). The anti-Markovnikov path leads to the formation of 4.29, which is in equilibrium with 4.24. Complexes 4.25 and 4.26 are analogues of 4.4 with //-butyl and /-butyl groups in the place of methyl. They reductively eliminate the linear and branched acid iodides. In the presence of water the acid iodides are hydrolyzed to give //-butyric and / -butyric acids. 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

The reductive elimination/oxidative addition is of practical importance in catalytic cycles, for example the rhodium/methyl iodide catalysed carbonylation of methanol. In organic synthesis the palladium or nickel catalysed cross-coupling presents a very common example involving oxidative addition and reductive elimination. A simplified scheme is shown in Figure 2.19 [17],... 

Reaction (9) generates methyl iodide for the oxidative addition, and reaction (10) converts the reductive elimination product acetyl iodide into the product and it regenerates hydrogen iodide. There are, however, a few distinct differences [2,9] between the two processes. The thermodynamics of the acetic anhydride formation are less favourable and the process is operated much closer to equilibrium. (Thus, before studying the catalysis of carbonylations and carboxylations it is always worthwhile to look up the thermodynamic data ) Under standard conditions the AG values are approximately ... 

Pseudo-first-order rate constants for carbonylation of [MeIr(CO)2l3]" were obtained from the exponential decay of its high frequency y(CO) band. In PhCl, the reaction rate was found to be independent of CO pressure above a threshold of ca. 3.5 bar. Variable temperature kinetic data (80-122 °C) gave activation parameters AH 152 (+6) kj mol and AS 82 (+17) J mol K The acceleration on addition of methanol is dramatic (e. g. by an estimated factor of 10 at 33 °C for 1% MeOH) and the activation parameters (AH 33 ( 2) kJ mol" and AS -197 (+8) J mol" K at 25% MeOH) are very different. Added iodide salts cause substantial inhibition and the results are interpreted in terms of the mechanism shown in Scheme 3.6 where the alcohol aids dissociation of iodide from [MeIr(CO)2l3] . This enables coordination of CO to give the tricarbonyl, [MeIr(CO)3l2] which undergoes more facile methyl migration (see below). The behavior of the model reaction closely resembles the kinetics of the catalytic carbonylation system. Similar promotion by methanol has also been observed by HP IR for carbonylation of [MeIr(CO)2Cl3] [99]. In the same study it was reported that [MeIr(CO)2Cl3]" reductively eliminates MeCl ca. 30 times slower than elimination of Mel from [MeIr(CO)2l3] (at 93-132 °C in PhCl). 

The main steps in the catalytic MeOH carbonylation cyde which were proposed for the Co catalysed process [2] have served, with some modification perhaps in the carbonylation of MeOAc to AC2O, to the present day and are familiar as a classic example of a metal catalysed reaction. These steps are shown in Eigure 5.1. They are of course, (i) the oxidative addition of Mel to a metal center to form a metal methyl species, (ii) the migratory insertion reaction which generates a metal acyl from the metal methyl and coordinated CO and (iii) reductive elimination or other evolution of the metal acyl spedes to products. Broadly, as will be discussed in more detail later, the other ligands in the metal environment are CO and iodide. To balance the overall chemistry a molecule of CO must also enter the cycle. 

The mechanism for the reaction is believed to be as shown in Eq. 15.170 (start with CH3OH, lower right, and end with CHjCOOH, lower left).180 The reaction can be initiated with any rhodium salt, e.g., RhCl3, and a source of iodine, the two combining with CO to produce the active catalyst, IRItfCO y. The methyl iodide arises from the reaction of methanol and hydrogen iodide. Note that the catalytic loop involves oxidative addition, insertion, and reductive elimination, with a net production of acetic acid from the insertion of carbon monoxide into methanol. The rhodium shuttles between the +1 and +3 oxidation states. The cataylst is so efficient that the reaction will proceed at atmospheric pressure, although in practice the system is... 

The complex tra//.s-[AuMe2-t-Bu(PPh3)], prepared by addition of methyl iodide to the mixed dialkylaurate(I), was found (230) to convert spontaneously to the corresponding isobutyl complex in solution. First-order kinetic behavior was observed, and the rate was diminished by the addition of free triphenylphosphine, and so a dissociative mechanism was proposed (Scheme 8). The isopropyl analog did not react similarly at room temperature, and heating caused reductive elimination. 

The carbonylation of methyl acetate to acetic anhydride is likely to become an industrial process in the near future 424,427 RhCl3-3H20 is typically used as catalyst precursor and an iodide promoter is used. A mechanistic study indicated that methyl iodide formed from the ester and HI is carbonylated as in acetic acid synthesis (Scheme 26). The resulting acyl, perhaps via reductive elimination of acetyl iodide, converts the acetic acid formed in the ester cleavage to acetic anhydride.428 430 [RhI(CO)(PPh3)2] also catalyzes the reaction though apparently more slowly than complex (95).430,431 The mechanism of this reaction is given in Scheme 27. 

Direct conversion of 14 to (+)-himbacine is achieved in a one-pot procedure by removing the BOC group with trifluoroacetic acid and reaction of the resulting free amine with aqueous formaldehyde and sodium cyanoborohydride. This reductive elimination furnishes the imine which is in situ reduced to the tertiary amine. Another common method for /V-methylation is the reaction with a base like sodium hydride and methyl iodide. But this method is not suitable for molecules with C-H acidic protons. 

Aldol-type products 301 with X = H have been transformed into xanthates (by reaction with CS2 and methyl iodide), which suffer radical reductive elimination by treatment with... 

Mankind has produced acetic acid for many thousand years but the traditional and green fermentation methods cannot provide the large amounts of acetic acid that are required by today s society. As early as 1960 a 100% atom efficient cobalt-catalyzed industrial synthesis of acetic acid was introduced by BASF, shortly afterwards followed by the Monsanto rhodium-catalyzed low-pressure acetic acid process (Scheme 5.36) the name explains one of the advantages of the rhodium-catalyzed process over the cobalt-catalyzed one [61, 67]. These processes are rather similar and consist of two catalytic cycles. An activation of methanol as methyl iodide, which is catalytic, since the HI is recaptured by hydrolysis of acetyl iodide to the final product after its release from the transition metal catalyst, starts the process. The transition metal catalyst reacts with methyl iodide in an oxidative addition, then catalyzes the carbonylation via a migration of the methyl group, the "insertion reaction". Subsequent reductive elimination releases the acetyl iodide. While both processes are, on paper, 100%... 

---