Macrolactonizations in the Total Synthesis of Natural Products

The aldol addition is one of the most important methods for stereoselective construction of carboncarbon bonds. New and powerful variants of these classical reactions have been developed in recent years.1 Two classes were mainly used for asymmetric induction in these reactions: the use of asymmetric modified enolates or electrophiles2 and the use of chiral Lewis acids.3 The chiral enolate or electrophile approach is much more general and gives high stereoselectivities due to the highly ordered nature of transition structures (“closed” transition models). The chiral center has to be removed after the completed aldol addition. To avoid this additional reaction step, a stategy is employed whereby achiral enolates can be reacted with achiral carbonyl compounds in the presence of additional chiral auxiliaries. This method requires the careful use of a chiral auxiliary.4 Unfortunately, however, stoichiometric amounts of the chiral information are necessary. Up to now and apart from enzymatic transformations, the so-called Mukaiyama reaction has opened an enantioselective and catalytic approach using chiral Lewis acids. This review covers the evolution of stereoselective Lewis-acid-mediated aldol-type addition up to the recent development of chiral Lewis acids. Mukaiyama et al. found that silyl enol ether reacts with carbonyl compounds in the presence of Lewis acids to give aldol products (for initial studies, see ref 5). The main advantages in the Mukaiyama approach are the chemoselectivity of the reaction and the possibility of stereoselective execution. Since the mid-1970s, the Mukaiyama reaction has become a useful method for chemoand regioselective carboncarbon bond formation.6 About 10 years later, investigations into stereochemical aspects of these reactions were initiated,7 and at the end of the 1980s, the development of chiral Lewis acids and thus the development of catalytic, enantioselective versions of the Mukaiyama reaction started.8 The reaction mechanism has not been explained yet. The most important fact is that Lewis acid enolates are not involved in this reaction.7 No transmetalation occurs. In this reaction, the Lewis acids coordinate with the carbonyl function leading to its activation.9 Two works published by Carreira and Shibasaki suggest the involvement of chiral metal enolates during the aldol addition (for copper enolates, see ref 10; for palladium enolates, see ref 11). Moreover, there is a marked stereochemical differRainer Mahrwald obtained his M.S. degree in chemistry from the MartinLuther-University, Halle, in 1973. In 1975 he joined the Institute “Manfred von Ardenne”, Dresden, where he obtained his Ph.D. in 1979 in the field of the synthesis of nuclesides. In 1980 he joined the Academy of Sciences in Berlin. There he worked in the field of total synthesis of prostaglandins. He pursued his formation as a postdoctoral fellow at Philipps-University, Marburg, in the group of Prof. M. T. Reetz (1991). Since 1994 he has been a lecturer at the Humbold-University. His main research interests have been associated with the development of catalytic stereoselective C−C bond formation. 1095 Chem. Rev. 1999, 99, 1095−1120

Diastereoselection in lewis-Acid-mediated aldol additions.

Synthesis of Polyquinane Natural Products: An Update.

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.

Modern aldol methods for the total synthesis of polyketides.

Financial support of the Spanish Ministry of Science and
Innovation (CTQ2012-38543-C03) and Generalitat Valenciana
(PROMETEO/2012/020) is acknowledged. V.M.-C. thanks the
Spanish Ministry of Science and Education for a predoctoral
fellowship (FPU AP2007-02562) and Generalitat Valenciana for
a VALi+d postdoctoral fellowship (APOSTD/2013/041).
M.D.P. thanks the Spanish Ministry of Education for a
postdoctoral fellowship and UGC India for a Startup Grant.

Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization

Enantio- and diastereoselective aldol reactions of achiral ethyl and methyl ketones with aldehydes: the use of enol diisopinocampheylborinates

Studies in Macrolide Synthesis: A Stereocontrolled Synthesis of Oleandolide Employing Reagent- and Substrate-Controlled Aldol Reactions of (S)-1-(Benzyloxy)-2-methylpentan-3-one

M. Anne Lister

Papers

Enantio- and diastereoselective aldol reactions of achiral ethyl and methyl ketones with aldehydes: the use of enol diisopinocampheylborinates

Studies in Macrolide Synthesis: A Stereocontrolled Synthesis of Oleandolide Employing Reagent- and Substrate-Controlled Aldol Reactions of (S)-1-(Benzyloxy)-2-methylpentan-3-one

Aldol condensations of chiral ethylketones: Control by chiral boron reagents.

Enantioselective aldol condensations: The use of ketone boron enolates with chiral ligands attached to boron.

Asymmetric aldol reactions using chiral boron reagents: Application to the synthesis of tirandamycin A