Modern Aldol Methods for the Total Synthesis of Polyketides

Abstract

The aldol reaction is one of the most important methods for the stereoselective construction of polyketide natural products, not only for nature but also for synthetic chemistry. The tremendous development in the field of aldol additions during the last 30 years has led to more and more total syntheses of complicated natural products. This Review illustrates by means of selected syntheses of natural products the new variants of the aldol addition. This includes aldol additions with various metal enolates, as well as metal-complex-catalyzed, organocatalytic, and biocatalytic methods.

Nickel‐Catalyzed Formation of a Carbon–Nitrogen Bond at the β Position of Saturated Ketones

“…[7] 1,3-Diphenylpropan-1-one (6) also failed to be converted into the b-enaminone (< 3 %), but the reaction afforded a 1:1 mixture of a,b-unsaturated ketone 7 and b-aminoketone 8 [Eq. (2)]. This observation suggests that the catalytic transformation of ethyl ketones 1 into b-enaminones 3 may proceed through the oxidation of 1 to an a,b-unsaturated ketone and the subsequent 1,4-addition of amine, as speculated in our working hypothesis.…”

Efficient Asymmetric Synthesis of Long‐Chain Polyketides Containing up to Ten Contiguous Stereogenic Centres by Double Chain Elongation

“…[1] Most applied synthetic approaches to polypropionates have been reviewed recently. [2][3][4] They all are multistep syntheses once functional group construction, semi-protection steps and stereogenic centre installation are taken into account. For practical, environmental and economic reasons it is desirable to reduce numbers of chemical operations to a minimum.…”

Acid controlled diastereoselectivity in asymmetric aldol reaction of cycloketones with aldehydes using enamine-based organocatalysts

“…13,14 Asymmetric aldol reactions of cycloketones with aldehydes provide an attractive strategy for the construction of b-hydroxy cycloketones which are important synthons for biological active molecules. 15 Highly enantioselective and diastereoselective reactions generating chiral compounds with two stereocenters in one step are valuable for asymmetric synthesis. [16][17][18][19][20][21][22] However, it is still a challenge to control the diastereoselectivity in such reactions, which is a vital task in pharmaceutical and bioorganic chemistry to supply any of the possible stereoisomers of the chiral product.…”