A-heteroatom-substituted carbonyl

A variety of methods are available for the stereochemical construction of these optically active a-heteroatom-substituted carbonyl compounds, and in recent years a large number of new procedures have been developed applying asymmetric catalysis to carbonyl compounds, or their equivalents, as substrates [1]. The trick to these reactions is the direct C-H to C-Het transformation, as outlined in... 

Tetradentate chiral proton donors have been used for the asymmetric protonation of samarium enolates formed by the Sml2 reduction of a-heteroatom-substituted carbonyl compounds. For example, Takeuchi examined the reduction of a-heterosubstituted cyclohexanone 12 using Sml2 and the BINOL-derived chiral proton source 13.41 Ketone 14 was obtained in good yield and high enantiomeric excess (Scheme 2.11). Coordination of the proton source to samarium is key to the success of the transformation.41... 

The Reduction of a-Heteroatom-substituted Carbonyl Groups with Sml2... 

The reduction of a-heteroatom-substituted carbonyl compounds is an excellent method for the generation of Sm(III) enolates that can be used in carbon-carbon bond-forming reactions (see Chapter 5, Section 5.5). 

In 1986, Molander carried out the first detailed study on the reduction of a-heteroatom-substituted carbonyl compounds with Sml2.29 It was shown that Sml2 could reduce a range of a-oxygenated ketones under mild conditions to give the parent ketone in good yields and with no over-reduction of the ketone carbonyl (Scheme 4.23). 

Representative procedure,29 To a solution of Sml2 in THF (2 equiv) at -78 °C was added the a-heteroatom-substituted carbonyl compound (1 equiv) in... 

A number of other (1-elimination processes have been developed by Concellon that are based on the reduction of a-heteroatom-substituted carbonyl compounds (Scheme 4.35).7... 

Intramolecular Sml2 aldol-type reactions involving a-heteroatom-substituted carbonyl compounds where the group expelled from the starting material is not a halogen have also been carried out. 

The origin of selectivity with the tartrate-based allylboronates is believed to result from the minimization of unfavorable electronic interactions. The two transition structures shown in Fig. 10-5 illustrate the interactions that contribute to the major and minor pathways. The electronic interactions are reasonable as they would arise from a favored conformation of the a-heteroatom-substituted carbonyl system, i.e. one in which the heteroatom and the carbonyl group are. yn-coplanar. It is interesting to note that the selectivity which would be predicted on steric grounds is opposite to that observed with the tartrate-based reagents. 

Deprotonation of a-heteroatom-substituted carbonyl compounds (at the carbon bearing the substituent) has been less studied. In several cases it has been observed that, if chelation of the counterion by the enolate is possible, the (Z)-enolate is the preferred compound. Garst and coworkers reported two examples in which an a-dialkylamino ketone gives ( )-enolates selectively, whereas die corresponding... 

The Mizoroki-Heck reaction promoted by microwave irradiation was first described by Laihed and Hallberg [205]. For easy catalyst recovery, solid-supported systems were often used. An a-heteroatom-substituted carbonyl linker has been utilized in solid-phase approaches to oxinolines by Pummerer cyclization [206]. The reaction performed with s/c = 20 in the presence of phosphine ligands (ratio ligand/palladium-precursor = 1 1) in 88-99% yield at 7 h reaction time. 

The development of suitable linkers is a continuous area of interest in solid-supported synthesis. Based on their previously explored traceless linking strategy using HASC (a-heteroatom-substituted carbonyl) linkers employing Smb, Procter and coworkers have demonstrated the use of a novel sulfur-based linker for the synthesis of the tetra-... 

Enolates from Conjugate Additions to a,fi-Unsaturated Carbonyl Compounds I.62J Enolates from Reduction of a-Heteroatom-substituted Carbonyl Compounds... 

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