Article

The condensation of methyl 2-methlylpropanoate with chiral aldehydes. X-ray crystal structure of (3rs,4sr) 3-hydroxy-4-phenyl-2,2,4-trimethylpentanoic acid

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The lithium enolate derived from methyl 2-methylpropanoate reacts stereoselectively with 2-phenylpropanal and 2-(cyclohexyl)propanal, affording mainly the β-hydroxy ester in both cases. With 2-ethylhexanal, no selectivity was observed.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

Chapter
Beim Studium der Carbonyladditionen haben wir bereits an zwei Stellen (Kapitel 5, Formeln 279 und 304) die Problematik der konjugierten Additionen1–10) gestreift. In beiden Fällen war deutlich die Unentschlossenheit des Nucleophils angesichts eines konjugierten delokalisierten Acceptorsystems sichtbar geworden. Zweifellos verlockt der höhere δ⊕-Charakter der Carbonylgruppe zur spontanen 1,2-Attacke (2). Wird jedoch nicht sofort durch weitgehend homöopolar gebundenes Gegenkation, unpolares Solvens und raschen Zugriff des Elektrophils bei tiefer Temperatur die Falle geschlossen (4) und der Rückweg abgeschnitten, so mag das bei der Wiederherstellung des konjugierten Systems herausgedrängte Nucleophil bei einem der folgenden Anläufe gelegentlich auch resignierend unter 1,4-Addition mit der etwas geringeren Ladungsdichte der ß-Position vorliebnehmen und somit über das Enolat 3 nach Fixierung der negativen Ladung im thermodynamisch stabilen Produkt der sogenannten Michael-Addition (5) zur Ruhe kommen. Daß dabei höher resonanzstabilisierte, bessere Fluchtgruppeneigenschaften aufweisende „weiche“ Nucleophile diesen Rückzug aus 2 leichter antreten können und somit aussichtsreichere Kandidaten für konjugierte Additionen sind, versteht sich von selbst und wird durch das Pearson-Reglement11) generalisiert (zu den Formeln 1–5 vgl. Schema I).
Article
Traditionally, aldol reactions were carried out under protic conditions, such that the enolate was formed reversibly. 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 three 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, boron and magnesium, and there now exists a considerable literature documenting certain aspects of lithium, boron and magnesiumenolate 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.
Article
Lithium enolates derived from the title esters show high diastereoface selectivity in their reactions with chiral aldehydes. The resulting 2,2-dithioaldols are desulfurized in good yield with Ni2B-H2 (EtOH, 20°C). With this mild desulfurization protocol, complete retention of stereochemical integrity was observed for all isolated aldols.
Article
Full-text available
A simple versatile enantiospecific synthetic route from camphor to the C,D ring system and side-chain unit of steroids has been developed.
Article
The level of 1,2-asymmetric induction in the BF3·OEt2-promoted addition of silyl ketene thioacetals to α-asymmetric aldehydes is affected by the bulk of the silyl group; unprecedented Cram-type selectivity is given by the triisopropylsilyl derivative 8a.
Article
Chiral enones show good to excellent diastereofacial preference in their TiCl4-mediated reactions with achiral and chiral enolsilanes; the method is shown to be useful for the preparation of acyclic 1,5-diketones and 1,5-keto acids having two or three stereocenters.
Article
BF3-OEt2 mediated thioester silylketene acetal additions to aldehydes are stereoconvergent and give high anti-syn ratios and good chemical yields. An acyclic transition state model was hypothesized in order to account for the observed selectivity. Theoretical methods (MNDO) were used to evaluate the ground-state conformations of thioester silylketene acetals and to model the acyclic transition states. Lewis acid mediated additions of thioester silylketene acetals to 2-phenylpropion-aldehyde (BF3-OEt2), O-benzyl lactic aldehyde (SnCl4), 2,3-0,O-dibenzyl glyceraldehyde (SnCl4), and 3-benzyloxy-2-methylpropionaldehyde (TiCl4) were found to be highly diastereoface selective so that three contiguous stereocenters could be established. With α-, β- , or α,β-alkoxy aldehydes, relative stereoselection (chelation) effectively controls internal stereolection. The ground state conformations of the chiral aldehydes were studied using molecular mechanics (MM2).
Article
The stereochemistry of the aldol condensation of preformed lithium enolates of a variety of ethyl ketones and propionic acid derivatives with aldehydes has been investigated. It is found that certain compounds give completely or nearly completely one diastereomeric enolate and that the stereostructure of the resulting aldol is correlated with the stereostructure of the enolate from which it is formed. The observed stereochemistry may be understood in terms of an ordered transition state in which both oxygens are oriented in more or less the same direction. It is shown that the observed stereochemistry is kinetically controlled. In many cases, the initial aldol adduct equilibrates to furnish predominantly a threo isomer. The rate of equilibration varies widely, ranging from very fast at -60°C with the propiophenone-benzaldehyde adduct to slow at 25°C for the ethyl tert-butyl ketone-benzaldehyde adduct. The equilibration behavior of lithium ketolates is compared with that of the zinc ketolates, and some differences are noted. A method for achieving erythro-threo equilibration via a chloral hemiacetal is presented. A new reagent is introduced (trimethylsilyloxy ketone 36) which may be used to stereoselectively homologate an aldehyde to an erythro α-methyl-β-hydroxy acid. As an application of the use of stereoselective aldol condensations in synthesis, (±)-ephedrine (48) has been synthesized from benzaldehyde in 71% overall yield.
Article
High Cram rule selectivity was observed in the zinc chloride catalyzed reaction of (E)-1-methoxy-3-[(trimethylsilyl)oxy]-1,3-butadienes with glyceraldehyde acetonide and with N-Boc-substituted leucinal. Conversion of the resultant dihydropyrones to other products of interest is described.
Article
The stereochemistry of the reaction of benzaldehyde with the magnesium enolate of phenylacetic acid has been studied. In addition to the known 178° isomer of 2,3-diphenyl-3-hydroxypropionic acid, its diastereomer, m.p. 144°, was isolated as a minor product. By means of a stereospecific degradation the former was shown to be the threo isomer while the latter was found to have the erythro configuration. The ratio of the diastereomeric reaction products was determined and a hypothesis advanced to account for the preferential formation of the threo isomer.
Article
A rule is proposed to correlate and predict the stereochemical direction of asymmetric induction in reactions of acyclic systems in which a new asymmetric center is created adjacent to an old: "In non-catalytic reactions of the type shown (Formulas), that diastereomer will predominate which would be formed by the approach of the entering group from the least hindered side of the double bond when the rotational conformation of the C-C bond is such that the double bond is flanked by the two least bulky groups attached to the adjacent asymmetric center." This rule successfully correlates the configurations of thirty-five compounds prepared by six different reactions of the above type, in each case the stereochemical relationships between the asymmetric carbons of the substances having been demonstrated by some independent means. This rule has been used to predict the configurations of fifty compounds whose stereochemical structures have been hitherto unknown.
Article
This manuscript describes a simple empirical model on the basis of which semiquantitative predictions of product stereospecificity, resulting from chemical additions to carbonyl groups directly bonded to asymmetric carbon atoms, are feasible. The model is based on the following assumptions, (a) Little bond breaking and making marks the diastereomeric transition states. The arrangement of the three groups of the asymmetric carbon atom with respect to the carbonyl is thus as in aldehydes and ketones, i.e., one group eclipsing the carbonyl. (b) The two low-energy diastereomeric transition states that control product stereospecificity have the smallest group of the asymmetric carbon atom closest to the incoming bulky group, (c) The diastereomeric ratio is then evaluated from the relative magnitudes of the carbonyl-eclipsed group interactions. With correspondence between calculated and experimentally determined product diastereomeric ratios being fairly good, several difficulties encountered with previous models are adequately rationalized.