Aldehydes dienolates, alkylation

For the reaction of 1,3-dioxin -ones with electrophiles, activation by deprotonation of the side-chain alkyl group is required. Typically lithium diisopropylamide (LDA) is used as a base. The resulting lithium dienolates react with aldehydes <2002EJ0718> or with allyl bromides in the presence of Ar,Ar -dimethylpropyleneurea (DMPU) <2005AGE820, 2006CEJ2488> exclusively at the side-chain double bond, albeit in modest yields (Equation 25). 

Oxamborolidenes. There are noteworthy advances in the design, synthesis, and study of amino acid-derived oxazaborolidene complexes as catalysts for the Mukaiyama aldol addition. Corey has documented the use of complex 1 prepared from A-tosyl (S)-tryptophan in enantioselective Mukaiyama aldol addition reactions [5]. The addition of aryl or alkyl methyl ketones 2a-b proceeded with aromatic as well as aliphatic aldehydes, giving adducts in 56-100% yields and up to 93% ee (Scheme 8B2.1, Table 8B2.1). The use of 1-trimethylsilyloxycyclopentene 3 as well as dienolsilane 4 has been examined. Thus, for example, the cyclopentanone adduct with benzaldehyde 5 (R = Ph) was isolated as a 94 6 mixture of diastereomers favoring the syn diastereomer, which was formed with 92% ee, Dienolate adducts 6 were isolated with up to 82% ee it is important that these were shown to afford the corresponding dihydropyrones upon treatment with trifuoroacetic acid. Thus this process not only allows access to aldol addition adducts, but also the products of hetero Diels-Alder cycloaddition reactions. 

In a synthesis of PGEt reported by Corey 89) for the preparation of the 0,S-acetal-protected dienol thioether aldehyde 122, the ylide generated from phosphonium salt 119 was used as an electrophile in the alkylation of 118. The following Wittig reaction of the resulting phosphonium salt 120 with the thioenolether aldehyde 121 in the presence of phenyllithium as the base gave intermediate 122 in 35% yield. 

Other efforts have been focused on a conceptually new, directed aldol condensation [54]. Mixed aldol condensations between two different carbonyl compounds with several possible sites for enolization are extremely difficult and there is a variety of undesired pathways involving proton transfer and over-alkylation. The aldol reaction of an a,/ -unsaturated carbonyl compound with an aldehyde was investigated in the presence of ATPH. The reaction first involves fhe demand for control of reactivity and selectivity of the a, -unsaturated carbonyl compound, which upon deprotonation leads to the corresponding extended dienolate of ATPH. A second carbonyl compound aldehyde which serves as an electrophile is activated electronically (but sterically deactivated) by complexation with ATPH. This activation would enable rapid in-situ capture of fhe extended dienolate. ATPH was the reagent of choice, because it could effectively make a strong coordination bond upon encapsulating a number of a, -unsaturated carbonyl compounds. 

A variation on a literature procedure draws attention to a useful method for the synthesis of tetrolic acid. Copper dienolates derived from a,jS-unsatur-ated acids undergo y-alkylation with a regioselectivity of 91%. A full paper has appeared from Mulzer and his co workers on the control of 1,2-/1,4-regioselectivity in the additions of carboxylic acid dianions to a,jS-unsaturated carbonyl compounds. The addition of phenyl acetate dianion (23) (Scheme 20) to a,/3-un aturated aldehydes leads to the f/ireo-unsaturated /S-hydroxy-carboxylic acid (24) the threo and erythro ratio of 5 examples was >9 1. 

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