Strategies carbonyl replacement

Recent developments have impressively enlarged the scope of Pauson-Khand reactions. Besides the elaboration of strategies for the enantioselective synthesis of cyclopentenones, it is often possible to perform PKR efficiently with a catalytic amount of a late transition metal complex. In general, different transition metal sources, e.g., Co, Rh, Ir, and Ti, can be applied in these reactions. Actual achievements demonstrate the possibility of replacing external carbon monoxide by transfer carbonylations. This procedure will surely encourage synthetic chemists to use the potential of the PKR more often in organic synthesis. However, apart from academic research, industrial applications of this methodology are still awaited. 

It is now nearly 40 years since the introduction by Monsanto of a rhodium-catalysed process for the production of acetic acid by carbonylation of methanol [1]. The so-called Monsanto process became the dominant method for manufacture of acetic acid and is one of the most successful examples of the commercial application of homogeneous catalysis. The rhodium-catalysed process was preceded by a cobalt-based system developed by BASF [2,3], which suffered from significantly lower selectivity and the necessity for much harsher conditions of temperature and pressure. Although the rhodium-catalysed system has much better activity and selectivity, the search has continued in recent years for new catalysts which improve efficiency even further. The strategies employed have involved either modifications to the rhodium-based system or the replacement of rhodium by another metal, in particular iridium. This chapter will describe some of the important recent advances in both rhodium- and iridium-catalysed methanol carbonylation. Particular emphasis will be placed on the fundamental organometallic chemistry and mechanistic understanding of these processes. 

From a commercial viewpoint potential benefits can accrue from operating the methanol carbonylation process at low water concentration, provided that catalyst stability can be maintained. Strategies to achieve this include (i) addition of iodide salts to stabilise the Rh catalyst, (ii) heterogenisation of the Rh catalyst on a polymer support to restrict the catalyst to the reactor and (iii) replacement of Rh by a more robust Ir catalyst. These strategies, along with others for improving catalyst activity, will be discussed in the following sections. 

A second strategy is to replace one atom by another close to it in the Periodic Table to reveal analogies and patterns of reactivity. For example, replacing a nitrogen atom by an oxygen atom may reveal analogies between the reactivity of nitriles and carbonyl compounds and between enamines and enols. It may also provide some useful ideas for synthetic methods. 

Some industrially important polymeric materials can be prepared using the basic strategies discussed earlier. A representative example can be found in the synthesis of polyesters using the carbonylative polycondensation of aromatic dibromides and diols (Fig. 1-30) [237]. The underlying principle is no different from the fundamentals of carbonylative coupling presented earlier in Section 1.5.1.3. Replacement of the diols with hydrazides 86 similarly yields poly(acylhydrazide)s 87 [238]. The catalytic... 

Strategy A ketone or aldehyde reacts with a phosphorus ylide to yield an alkene in which the oxygen atom of the carbonyl reactant is replaced by the =CR2 of the ylide. Preparation of the phosphorus ylide itself usually involves 8 2 reaction of a primary alkyl halide with triphenylphosphine, so the ylide is typically primary, RCHP(Ph)j. This means that the disubstituted alkene carbon in the product comes from the carbonyl reactant, while the mono-substituted alkene carbon comes from the ylide. 

Strategy Acid-catalyzed reaction of an aldehyde or ketone with 2 equivalents of a monoalcohol or 1 equiv alent of a diol yields an acetal, in which the carbonyl oxygen atom is replaced by two -OR groups from the alcohol. 

Because of the wide occurrence of proteolytic hormones involved in various diseases, peptidomimetic inhibitors based on incorporation of a transition-state analog with a tetrahedral carbon to replace the carbonyl carbon of the sessile amide bond have been a dominant strategy. The simplest analog replaces the amide with a methylene amine, or a reduced amide bond. 

An intramolecular allyl silane/N-sulfonyl iminium ion cyclization has also been used as a pivotal step in an approach to the tricyclic core of the unique marine alkaloid sarain A [46]. The starting material was aziridine ester 129 (Scheme 25) which was elaborated to amide 130. An important step in the synthetic strategy was thermolysis of 130 to an azomethine ylide, which underwent stereospecific intramolecular 1,3-dipolar cycloaddition with the Z-alkene to produce bicyclic lactam 131 [47]. This compound was then elaborated into allyl silane 132. It was then possible to replace the lactam N-benzyl functionality with a tosyl moiety, leading to 133, and subsequent reduction of the carbonyl group afforded the desired cyclization precursor a-hydroxy sulfonamide 134. Exposure of 134 to ferric chloride promoted cyclization to a single stereoisomeric tricyclic amino alkene 136 having the requisite sarain A nucleus. It is believed that the intermediate N-sulfonyl iminium ion cyclizes via the conformation shown in 135. 

Aminoheterocycle bioisosteric approaches to amide groupings are exemplified in a report on soluble epoxide hydrolase inhibitors [5j. The replacement of the amide grouping in 1 by adoption of the tethering strategy of linking the carbonyl to adjacent side chains or benzene rings produced 2 (Figure 3.2). 

Boron carbonyl (BCO) fragment is isolobal to a CH group. This relationship predicts BCO might mimic the aromaticity of their hydrocarbon counterparts. In 2003, Schleyer et al. applied this strategy to convert delocalized structure of SBV into bishomoaromatic minima by BCO replacement at appropriate positions (Fig. 4.11). 

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