Carbonyl compounds chemoselectivity

Addition to Carbonyl Compounds. Unlike Grignard and alkykitliium compounds, trialkylboranes are inert to carbonyl compounds. The air-catalyzed addition to formaldehyde is exceptional (373). Alkylborates are more reactive and can transfer alkyl groups to acyl halides. The reaction provides a highly chemoselective method for the synthesis of ketones (374). 

Chemoselective reduction of a,(3-epoxy carbonyl compounds to aldols and their analogs by organoseleniums and its application to natural product synthesis 98YGK736. 

Me- SiCl also affects the stereoselectivity of 1,2-additions to carbonyl compounds [ 133]. Witli the aid of suitable activators, these mildly reactive reagents show selec-tivities unattainable by the conventional reagents, as ilustrated below for Me- SiCl-dependent Chemoselectivity fEq. 10.13) [134]. 

It has been reported that an allylic C-Si bond can be cleaved by tetrabutylammonium fluoride to give an anionic allylic species, which chemoselectively adds to carbonyl compounds (nitriles, esters, and epoxides failed) to form homoallylsilyloxy compounds13. 

Ballini and coworkers have developed a new strategy for alkenylation of carbonyl compounds based on the Michael addition followed by elimination of HN02 (see Section 7.3). A variety of 2-alkylidene 1,4-dioles have been conveniently prepared, in two steps, by the Michael addition of a nitroalkane to the appropriate enedione derivatives under basic conditions, followed by chemoselective reduction with LiAlH4 (Eq. 4.123).170... 

The Chemoselective Conversion of Carbonyl Compounds to Nitriles Ethyl 4-Cyanopentanoate. 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

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 initially formed titanium enolate 80 adds, in a diastereoselective fashion, to the electrophilic center of the activated oxime. The generated adduct 81 cyclizes chemoselectively to afford the desired /f-azetine, which is converted, with retention of configuration, to the corresponding /3-amino carbonyl compounds 82 via 3V-acetylation followed by hydrolysis. 

Asymmetric reduction of carbonyl compounds can usually be achieved either through direct catalytic hydrogenation or by metal hydride reduction. It should be mentioned here that reduction of carbonyl compounds by catalytic hydrogenation may not be chemoselective. Other co-existing functional groups such as the C=C bond may also undergo hydrogenation. 

T. Akiyama, J. Iwai, Scandium Trifluoromethane-sulfonate-Catalyzed Chemoselective Allylation Reactions of Carbonyl Compounds with Tetraallylgermane in Aqueous Media Tetrahedron Lett. 1997,38, 853-856. 

A study of the influence of the nature of the solid support showed that silica, celite, cellulose or magnesium sulphate in combination with borohydride can also be used successfully in the microwave-assisted reduction of carbonyl compounds. The choice of the solid support has been reported to influence the chemoselectivity of the reduction of chalcone. Under optimised conditions the reduction of the alkene can be suppressed using borohydride on silica, whereas the use of cellulose as solid support seems to favour C=C reduction (Scheme 4.11 )27. 

An Example of Chemoselectivity Relative Reactivities of Carbonyl Compounds with Respect to Nucleophiles... 

Mannam S, Alamsetti SK, Sekar G (2007) Aerobic, chemoselective oxidation of alcohols to carbonyl compounds catalyzed by a DABCO-copper complex under mild conditions. Adv Synth Catal 349(14-15) 2253-2258... 

A. Padwa, D. J. Austin, Ligand Effects on the Chemoselectivity of Transition Metal Catalyzed Reactions of a-Diazo Carbonyl Compounds, Angew. Chem. Int. Ed. Engl. 1994, 33, 801-811. 

However, if one of the aforementioned nucleophiles and the acylating agent are reacted in a 1 1 ratio, it is under certain circumstances possible to stop the reaction chemoselectively at the stage of the carbonyl compound C. 

Accordingly, if one wants to react a nucleophile and carboxylic acid derivative to produce a carbonyl compound in a chemoselective fashion via the mechanism of Figure 6.2, then one should use acid chlorides or comparably strongly activated carboxylic acid derivatives. In addition, the reaction must be carried out with the weakest possible nucleophile because only... 

Chemoselectivity of the Addition of Hydride Donors to Carbonyl Compounds... 

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