Organolithium compounds carbonylation

The reactions of organolithium compounds with carbonyl compounds, including carbon dioxide, may be interpreted as follows ... 

Organolithium compounds can add to a, (3-unsaturated ketones by either 1,2- or 1,4-addition. The most synthetically important version of the 1,4-addition involves organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is observed under some conditions even in the absence of copper catalysts. Highly reactive organolithium reagents usually react by 1,2-addition, but the addition of small amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation of the lithium ion, which attenuates its Lewis acid character toward the carbonyl oxygen.111... 

The most important reactions of Grignard reagents and organolithium compounds are the nucleophilic attack to the carbonyl group. 

The relative rates for various organolithium compounds are para-tolyl > phenyl > ethyl > isopropyl. As for the ketone, the rate is enhanced by electron-withdrawing substituents which increase the coordinating power of the carbonyl carbon. It therefore appears that the crucial step is the electrophilic attack by the carbonyl on the group R of the organolithium compound. 

Organolithium compounds are highly reactive and have been used in a variety of organic transformations. A major problem in the development of catalytic asymmetric conjugate additions of organolithium reagents to a,/3-unsaturated carbonyl compounds is that the high reactivity of RLi may cause both low chemoselectivity (1,2- vs. 1,4-addition) and low enantioselectivity. 

The principal disadvantage of this procedure is that the olefin must be used in at least three- to fourfold excess in order to obtain reasonable yields. In case of rare olefins, or of olefins containing groups such as the carbonyl group which add organolithium compounds, other methods might be more advantageous. The method is also limited to the preparation of secondary cyclopropanols. 

In this second case, the results of the calculations were in good agreement with the experimental data . The organolithium compound with the RC=0 coordinated in the proposed /rs fashion may now explain the significant shift of the carbonyl stretching mode from 2047 cm in n-BuLi—CO to 1635 cm in w-Bu—C(0)Li (equation 1). 

The reaction shown in Scheme 39 was also performed starting from a chiral carbamoyl chloride (91, Y = O) derived from (f )-iV-methyl-iV-(l-phenylethyl)amine, in order to study the possible asymmetric induction using prochiral carbonyl compounds. Thus, with pivalaldehyde or benzaldehyde the mixture of diastereomers obtained was ca 1 1. This behavior was also observed with other chiral functionalized organolithium compounds ". ... 

Another type of sp -hybridized S-oxido functionahzed organolithium compounds has been easily prepared from chloroacetic acid (149). After a double deprotonation with lithium diisopropylamide in THF at —78°C, a DTBB catalyzed (5%) hthiation in the presence of different carbonyl compounds as electrophiles at the same temperature followed by final hydrolysis afforded the expected S-hydroxy acids 151. The corresponding intermediate 150 was probably involved in the process (Scheme 54)" . 

Coldham and coworkers have shown that the asymmetric deprotonation protocol can be used to regioselectively alkylate the 5-position of imidazolidines (Scheme 35). The process is used as part of a sequence that results in asymmetric alkylation of 1,2-diamines with high stereoselectivity. The yields are limited, in this case, by the barrier to rotation around the carbamate C—N bond. Thus, only the amide rotamer having the carbonyl group syn to C-5 of the heterocycle is deprotonated. There are several examples in this review where this limitation is possible whether it is a factor or not may depend on the temperature at which amide bond rotation occurs versus the stability of the organolithium compound. In this case, the barrier to amide bond rotation was determined as 16.6 kcalmoD at 60 °C. 

Metalations with organolithium compounds, 8, 6 26, 1 27, 1 Methylenation of carbonyl groups, 43, 1 Methylenecyclopropane, in cycloaddition reactions, 61, 1... 

What about the applicability of organolithium compounds of type 29 with heavy organoelement groups in organic synthesis At present we can realize three modes of use (Scheme 39). The antimony compound is suitable as a reagent for nucleophilic halomethylation Nucleophilic lithiomethylation and carbonyl olefination, two other modes of application, are the objects of Sects. 4.4,4.5, and Chap. 5. 

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

An acyl group can be introduced into the 4 position of an a,p-unsaturated ketone by treatment with an organolithium compound and nickel" carbonyl.546 The product is a 1,4-... 

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