Enol chemoselective carbonylation reactions

Chemoselective Carbonylation Reactions of Enol Triflates and lodoalkenes... 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

We have concentrated so far on two functional groups within the same molecule. The chemoselectivity problem is just as important when we want two molecules to react together in a certain way, but, because both molecules have similar functional groups, the reaction can occur the other way round, or one of the molecules may react with itself and ignore the other. This problem is particularly acute in reactions involving enolisation. The alkylation or acylation of ends or enolates and the reaction of one carbonyl compound with another, the aldol reaction, are classical and important examples summarised in the general scheme below. We shall concentrate in this chapter on the chemoselectivity of these processes, that is we shall look at the enolisation of esters, aldehydes, and the like. 

Triflates derived from phenols are carbonylated to form aromatic esters by using Pd-Ph3P. The carbonylation of triflates is 500 times faster if DPPP (XLIV) is used [219]. This reaction is a good preparative method of benzoates from phenols and naphthoates from naphthols [220]. Carbonylation of enol triflates derived from ketones and aldehydes affords a,/Cunsaturated esters. The enol triflate in 451 is more reactive than the aryl triflate and the carbonylation proceeds stepwise chemoselectively. At... 

Fig. 9.5. Comparison of sulfonium and sulfoxonium ylides II—chemoselectivity in the reaction with an a,/3-unsaturated carbonyl compound. The sulfoxonium ylide reacts through the enolate intermediate A, whereas the sulfonium ylide reacts through the alkoxide intermediate B.

Highly coordinated silyl enolates have been studied more than highly coordinated tin enolates and they are reported to accelerate the reactions with both organic halides and carbonyl compounds . Compared to the silyl moiety, the system using highly coordinated tin enolates has unique characteristics which can be applied to obtain chemoselective reactions. Baba and coworkers reported a computational study of the difference between uncoordinated and highly coordinated tin enolates and their reactivities toward organic halides and carbonyl compounds. 

Allylation. Tin enolates prefer reaction with allylic halides to carbonyl compounds in the presence of Bu NBr. Thus, the chemoselectivity is reversed by this salt. 

Reactions in which the enol or enolate (or equivalent) of one carbonyl compound reacts with an electrophilic carbonyl compound (usually both are aldehydes or ketones) are often loosely called aldol reactions. In the last chapter we saw how the use of lithium enolates and other specific enolate equivalents conquers the problem of chemoselectivity in enolisation of aldehydes and acid derivatives. In this chapter, we are going to use the same intermediates to solve the problem of regioselectivity in crossed aldol reactions in which the enolising component is an unsymmetrical ketone. 

The reaction, if not controlled, can give a very complicated mixture of products due to reactivity, chemoselectivity, regioselectivity, and stereoselectivity issues. The synthesis of aldols with defined stereocenters in an efficient diastereo- and enantio-controlled fashion can be achieved with nature s aldolaze enzymes [2]. Their ability to control the enantioselectivity of the direct aldol reaction led chemists to the development of one of the most important C-C bond formation reactions. In the modem aldol reaction, a preformed enolate is added to a carbonyl compound even though the direct cross-aldol reaction is a more attractive approach [3]. 

Second, functional group selectivity is observed - i.e. reactions with aldehydes proceed at —78 °C whereas those with ketones proceed at elevated temperatures (ca. 0 °C). Chemoselectivity is observed with acceptors having two different kinds of carbonyl function, for example aldehyde and ketone or ester, in the same molecule. Treatment of phenylglyoxal with silyl enol ether 38 at —78 °C affords a-hydroxy-y-diketone 39 (Eq. (20)) [20b]. The reaction of ketoesters 40 other than j5-ketoesters with silyl enol ether 38 gives hydroxyketoesters 41 as sole products (Eq. (21)) [23]. 

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