Clayton H. Heathcock

Acyclic Stereocontrol Through the Aldol Condensation

For the scientist who wishes to synthesize complex organic compounds, the most difficult problem is often establishing the correct configuration at the various chiral centers as the synthesis is being carried out. In the past decade, there has been an increasing effort to find direct solutions to this problem, which is particularly acute in the synthesis of acyclic and other conformationally flexible molecules. One of the oldest organic reactions, the aldol condensation, is emerging as a powerful tool for use in achieving such stereocontrol.

Acyclic stereoselection—13 : Aryl esters: reagents for threo-aldolization

Abstract Preformed Li enolates of hindered aryl esters condense with aldehydes to give predominantly threo aldols. The method has been explored with esters 3 (DMP propionate), 4 (BHT propionate), and 5 (DBHA propionate). DMP propionate reacts with benzaldehyde and α-unbranched aliphatic aldehydes to give threo:erythro ratios of about 6.5:1. However, with α-branched aliphatic aldehydes, ester 3 gives only threo-aldols. BHT propionate and DBHA propionate give only threo-aldols with all aldehydes studied. The DMP aldols may be converted into β-hydroxy acids by simple hydrolysis with KOH in aqueous methanol. BHT aldols cannot be hydrolyzed without retroaldolization. However, these aldols can be reduced to diastereomerically pure 1,3-diols. The DBHA aldols can be converted into β-hydroxy acids by a method involving oxidation with ceric ammonium nitrate (CAN) in aqueous acetonitrile. Threo-selectivity is also seen in the condensations of DMP butyrate (15), DBHA butyrate (16), DMP pentenoate (17), and BHT pentenoate (18). The approach has been utilized in a stereoselective synthesis of racemic methyl corynomycolate (30).

The synthesis of mevinic acids

Article de synthese en 3 parties: synthese totale des mevinoline et compactine; synthese des fragments «hexaline» et «octaline» des composes precedents et de leurs derives dihydrogenes; synthese de la partie lactone

Acyclic stereoselection. XXXII: Synthesis and characterization of the diastereomeric (4S)-pentane-1,2,3,4-tetrols

Stereochimie de la reaction entre les enolates de lithium du benzyloxy acetate de methyle, du benzyloxy cetene bis-trimethylsilyl acetal et le benzyloxy-2 propanal

Acyclic stereoselection. 27. Simple diastereoselection in the lewis acid mediated reactions of enolsilanes with aldehydes.

Abstract The Lewis acid mediated reactions of enolsilanes 1–11 with benzaldehyde and isobutyraldehyde have been investigated. With the exception of compound 4, essentially no stereoselectivity is observed.

Total synthesis of (−)-mirabazole C

The tetrathiazoline marine alkaloid (-)-mirabazole C (7) has been synthesized by cyclization of a diamide derivative of the tripeptide derived from (R)-2-methylcysteine

1.5 – The Aldol Reaction: Acid and General Base Catalysis

An ‘aldol’ reaction is the reaction of one carbonyl compound, acting as a nucleophile in the form of its enol or enolate derivative, with another, acting as an electrophile. The two carbonyl compounds may or may not be the same. The general reaction is subject to either acid or base catalysis. The initial product is a β-hydroxycarbonyl compound. Under some conditions, this primary product undergoes dehydration, resulting in an α,β-unsaturated carbonyl compound. In this chapter, we summarize the aldol reaction from a historical perspective and point out the limitations of the reaction as it was generally used prior to about 15 years ago.1 Succeeding chapters treat the aldol reaction as it is usually practiced today, in a ‘directed’ manner, using ‘preformed’ enolates.2 As will be seen in the sequel, an understanding of the factors regulating the stereochemistry of the aldol reaction has been largely responsible for the rebirth of this venerable reaction in the last 15 years.3

Synthesis, structure, and carbon-carbon bond-forming reactions of carbon-bound molybdenum, tungsten, and rhenium enolates. Detection of an .eta.3-oxaallyl intermediate

Preparation des enolates des metaux de transition lies par C et caracterisation. Observation des reactions photochimiques aldoliques pour les complexes de W et Mo. Structure moleculaire

Fluoride-catalyzed conversion of acylsilanes to aldehydes and ketones

Abstract Acylsilanes undergo efficient protodesilylation upon treatment with fluoride ion in moist DMSO, HMPT, or THF. The reaction is also catalyzed by methoxide ion in methanol or DMSO, but not by chloride ion or bromide ion. Fluoride-catalyzed desilylation in the presence of alkyl halides, aldehydes, or ketones results in modest yields of the corresponding alkylated products.

1.6 – The Aldol Reaction: Group I and Group II Enolates

Traditionally, aldol reactions were carried out under protic conditions, such that the enolate was formed reversibly (see Volume 2, Chapter 1.5). An added measure of control is possible if one uses a sufficiently strong base that the enolate may be quantitatively formed prior to addition of the electrophile. The renaissance that has occurred in the aldol reaction in the last two decades has been mainly due to the development of methods for the formation and use of preformed enolates. The simplest enolates to prepare are those associated with lithium and magnesium, and there now exists a considerable literature documenting certain aspects of lithium and magnesium enolate aldol chemistry. This chapter summarizes the aldol chemistry of preformed enolates of these Group I and Group II metals. Other chapters in this volume deal with boron enolates, zinc enolates, transition metal enolates and the related chemistry of silyl and stannyl enol ethers.