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.

The preparation, analysis, and reactions of novel, highly stereoselective cyclopentadienyldialkoxyallyltitanium reagents, available in both enantiomeric forms, are described. Chiral monochlorotitanates are readily prepared from CpTiCl 3 or Cp.TiCl 3 and chiral 1,4-diols, which in turn are obtained from tartrate ester acetals by Grignard addition. The resulting stable seven-membered titanacycles have been analyzed by 1 H, 13 C, and 49 Ti NMR spectroscopy. The structures of two representatives, the complexes 15 and 20, are confirmed by X-ray diffraction

Enantioselective syntheses with titanium carbohydrate complexes. Part 7. Enantioselective allyltitanation of aldehydes with cyclopentadienyldialkoxyallyltitanium complexes

The SAMP-/RAMP-hydrazone methodology in asymmetric synthesis

More with boron: The development of catalytic enantioselective 1,2-diboration of 1,3-dienes enables a new strategy for enantioselective carbonyl allylation reactions (see scheme). These reactions occur with outstanding levels of stereoselection and can be applied to both monosubstituted and 1,1-disubstituted dienes. The carbonyl allylation reactions provide enantiomerically enriched functionalized homoallylic alcohol products.

Catalytic Enantioselective 1,2-Diboration of 1,3-Dienes: Versatile Reagents for Stereoselective Allylation

The reactions of Hoppe’s lithiated carbamates with vinylboranes and boronic esters give allylic boranes/boronic esters, and subsequent addition of aldehydes provides a new route to enantioenriched homoallylic alcohols with high enantiomeric ratios and diastereomeric ratios Specifically, reactions of sparteine-complexed lithiated carbamates with trans-alkenyl-9-BBN derivatives followed by addition of aldehydes gave (Z)-anti-homoallylic alcohols in greater than 95:5 er and 99:1 dr However, in the special case of the methyl-substituted lithiated carbamate, diamine-free conditions were required to achieve high selectivity Reactions of sparteine-complexed lithiated carbamates with (Z)-alkenyl pinacol boronic esters and (E)-alkenyl neopentyl boronic esters gave (E)-syn- and (E)-anti-homoallylic alcohols, respectively, in greater than 96:4 er and 98:2 dr In these reactions, a Lewis acid (MgBr2 or BF3·OEt2) was required to promote both the 1,2-metalate rearrangement and the addition of the intermediate allyli

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Application of the lithiation-borylation reaction to the preparation of enantioenriched allylic boron reagents and subsequent in situ conversion into 1,2,4-trisubstituted homoallylic alcohols with complete control over all elements of stereochemistry.

Pentenylboronates, either >90% Z (4) or >95% E (3), can be obtained by reaction of the pentenyl Grignard reagent with different borates. The Z-pentenylboronates 4 add to aldehydes under high simple diastereoselection to give the diastereomerically pure syn-homoallyl alcohols 10. The corresponding addition of the E-pentenylboronates leads to the anti-homoallyl alcohols as E-(15)/Z-(17) mixtures.



Stereoselektive Synthese von Alkoholen, XXX. — E- und Z-Pentenylboronsaureester, Reagenzien, die sich unter einfacher Diastereoselektivitat an Aldehyde addieren



Durch Reaktion des Pentenyl-Grignard-Reagenzes 2 mit verschiedenen Borsaureestern erhalt man Pentenylboronsaureester entweder zu >90% als Z-Isomer 4 oder zu >95% als E-Isomer 3. Addition der Z-Pentenylboronsaureester 4 an Aldehyde ergibt die diastereomerenreinen syn-Homoallylalkohole 10. Entsprechende Addition des E-Pentenylboronsaureesters 3 fuhrt zu anti-Homoallylalkoholen als E-(15)/Z-(17)-Gemische.

Stereoselective synthesis of alcohols, XXX: E‐ and Z‐pentenylboronates, reagents for simple diastereoselection on addition to aldehydes

The total synthesis of the denticulatins 1 is described. Key feature is the efficient generation of the C-1-to-C-9 building block 37 by three consecutive stereoselective carbon - carbon bond-forming steps using chiral allylboronates. The C-10-to-C-17 building block was obtained by kinetic Sharpless resolution of an allylic alcohol followed by an Ireland-Claisen rearrangement.

Stereoselective Synthesis of Alcohols, XXXVIII Stereoselective Total Synthesis of the Denticulatins

The stereotriad D has been the most elusive one to obtain in the course of the synthesis of polyketide derived natural products. Many research groups involved in such endeavours have contributed original approaches to this seemingly simple structural unit. The most popular approach is to generate a building block that contains all the stereocenters of the triad D. The molecular skeleton may then be extended from such a buil- ding block in two directions. We describe here our own route to such building blocks, being based on an enantioselective crotylboration of methacrolein followed by a diastereoselective hydroboration reaction

Marc W. Andersen

Papers

Stereoselective synthesis of alcohols, XXX: E‐ and Z‐pentenylboronates, reagents for simple diastereoselection on addition to aldehydes

Stereoselective Synthesis of Alcohols, XXXVIII Stereoselective Total Synthesis of the Denticulatins

Stereoselective Synthesis of Alcohols, XLV:1Recent Developments in the Generation of the Stereotriad "D"

Efficient Stereoselective Total Synthesis of Denticulatins A and B

Effiziente stereoselektive Totalsynthese der Denticulatine A und B