Enantiopure Aldehydes Research Articles

Meso-tetra(dioxanyl)porphyrins: Neutral, low molecular weight, and chiral porphyrins with solubility in aqueous solutions

The synthesis of the low-molecular weight, meso-tetra(dioxan-2-yl)porphyrin with considerable solubility in aqueous solution is described. The key intermediate dioxan-2-carbaldehyde is accessible in either racemic or in stereo-pure forms from commercially available starting materials in three steps. Using 4 × 1 or 2 + 2-type syntheses provide the porphyrin in modest yields. While the racemic aldehyde created an intractable mixture of diastereomers, the enantiopure aldehyde created a single enantiomer of the target porphyrin. The porphyrin was spectroscopically characterized. As its free base or zinc complex, it showed excellent solubility properties in organic and aqueous solvents, though free water-solubility was not achieved. The work expands on the availability of chiral porphyrins and neutral porphyrins with considerable solubility in aqueous solution.

Transition-Metal-Free Homologative Cross-Coupling of Aldehydes and Ketones with Geminal Bis(boron) Compounds.

We report a transition-metal-free coupling of aldehydes and ketones with geminal bis(boron) building blocks which provides the coupled, homologated carbonyl compound upon oxidation. This reaction not only extends an alkyl chain containing a carbonyl group, it also simultaneously introduces a new carbonyl substituent. We demonstrate that enantiopure aldehydes with an enolizable stereogenic center undergo this reaction with complete retention of stereochemistry.

Unified total synthesis of (+)-chinensiolide B and (+)-8-epigrosheimin.

An expedient synthetic approach has been developed for the unified total synthesis of (+)-chinensiolide B and (+)-8-epigrosheimin. The point of divergence was provided by the lactone aldehyde 6, in which four contiguous stereocenters were achieved by a stereocontrolled Evans syn-aldol reaction of a R-carvone derived enantiopure aldehyde and chiral N-succinyl-oxazolidinone. The lactone aldehyde 6 was synthesized in multigram quantity in three steps. Highly optimized chemo- and stereoselective reactions and functional group interconversion enabled us to assemble (+)-chinensiolide B and (+)-8-epigrosheimin from 6.

Diastereoselective Pictet–Spengler Reactions of a Tethered 2-Aminoimidazole

The diastereoselective Pictet–Spengler reaction of aminopropyl-2-aminoimidazole with enantiopure aldehydes has been investigated. With amino acid-derived aldehydes, anti stereochemistry is favoured, with a diastereoselectivity up to 92 % achievable. The absolute stereochemistry of the products was determined through synthesis of a rigid derivative and from NMR data in combination with molecular modelling. The diastereoselectivity was shown to be dependent on the steric bulk of the amino acid side chain and independent of the nitrogen protecting group. Lewis acids catalysed the reaction but did not affect the diastereoselectivity.

Direct asymmetric syntheses of chiral aldehydes and ketones via N-acyl chiral auxiliary derivatives including chiral Weinreb amide equivalents

This article covers N-acyl chiral auxiliary-based approaches to the asymmetric synthesis of enantiopure aldehydes and ketones. The use of diastereoisomerically pure N-acyl derivatives of chiral auxiliaries (including chiral Weinreb amide equivalents) and their conversion to the corresponding enantiopure aldehydes and ketones in a single synthetic operation by treatment with a hydride reducing agent or an organometallic reagent, respectively, are highlighted.

ChemInform Abstract: Formation of Multi‐Stereogenic Centers Using a Catalytic Diastereoselective Henry Reaction.

AbstractA diastereomeric Henry reaction of enantiopure aldehydes (V) is developed using a chiral sulfonyl diamine/CuCl complex as catalyst.

Isolation, Enantioselective Total Synthesis and Structure Determination of the Anthrapyran Metabolite SS 43405‐e

AbstractThe first enantioselective total synthesis of the anthrapyran metabolite SS 43405‐e, isolated from a marine‐derived streptomycete, is described, which also allows the determination of the so far unknown absolute (R) configuration of the natural product. For the synthesis the bromoanthracene derivative 3 is lithiated and coupled with the enantiopure aldehyde (S)‐4 to give 9, which is oxidatively transformed into the corresponding anthraquinone 10 and further into the ketone 2. The final step is the cyclization of 2 under acidic conditions to give the desired antibiotic (S)‐1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Stereoselective Synthesis of Vicinal Aminodiols, Diamines and Diaminols by the Use of Enantiopure Aldehydes in the Three‐Component Aromatic Mannich‐Type Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Stereoselective synthesis of vicinal aminodiols, diamines and diaminols by the use of enantiopure aldehydes in the three-component aromatic Mannich-type reaction

A short and stereoselective synthesis of vicinal aminodiols, diamines and diaminols obtained in good yields, through a three-component aromatic Mannich-type reaction, is reported. Enantiopure aldehydes containing stereogenic centres and functionalized with variously protected amino and hydroxy groups successfully afforded enantiopure aminoalkylnaphthols. Conformational analysis, compared with 1H NMR data of the products obtained, allows the attribution of the absolute configuration, also confirmed by X-ray analysis.

Uncatalyzed Mukaiyama–Michael Reaction: Rapid Access to Simple and Complex Enantiopure γ‐Butenolides

A simple start: A tungsten carbene 3, 2-trimethylsilyloxyfuran (4), and an enantiopure aldehyde 5 provide easy access to enantiopure butenolides 2. The metal carbene increases the accepting character of the CC bond and allows further transformations into butenolide structures such as 1.

Asymmetric Construction of Quaternary Carbon Stereocenters: High Stereoselection in Mukaiyama Aldol Reactions of 2‐Siloxyindoles with Chiral Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Construction of Quaternary Carbon Stereocenters: High Stereoselection in Mukaiyama Aldol Reactions of 2-Siloxyindoles with Chiral Aldehydes

[reaction: see text] A new synthesis of enantiopure 3,3-disubstituted oxindoles by stereoselective Mukaiyama aldol reaction of 3-substituted 2-siloxyindoles and chiral, enantiopure aldehydes having nitrogen or oxygen substituents at the alpha carbon is described. When the C3 substituent of the prochiral nucleophile is aryl or heteroaryl, stereoselectivity is high (10-80:1).

Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals: Synthesis and Characterization

AbstractA synthetic route to a series of homochiral (and achiral) nitronyl nitroxides derived from rac‐(and meso)‐3,4‐dimethyl‐3,4‐dinitrohexane is described. The two forms of this precursor, meso and rac, were identified unambiguously and reduced to the corresponding meso‐ and rac‐diamines. The rac‐diamine was condensed with an enantiopure aldehyde specifically designed to give a diastereomeric mixture of imidazolidines easily separated by flash chromatography. Both enantiopure diamines were then obtained by acidic hydrolysis of these imidazolidines. The absolute configurations of the diamino precursors were determined by X‐ray crystallography of single crystals of a manganese(II) complex [(R,R,R)‐5E·Mn(hfac)2] of a nitroxide containing a third chiral center of known configuration. A series of homochiral nitronyl nitroxides was then prepared from the enantiopure diamino precursors by condensation with aldehydes, followed by oxidation. Their structural properties were compared to those of their achiral meso counterparts and it was found that the puckering of the five‐membered ring is dependent on the chirality of the imidazolyl unit. The radicals show marked optical activity, as explored by polarimetry and circular dichroism spectroscopy. These paramagnetic building blocks of known absolute configuration include chiral centers adjacent to the oxyl groups, and since they exhibit C2 symmetry they are well suited for coordination chemistry studies because stereochemical complexity is minimized. They have been specifically designed for further developments of the metal‐radical approach to molecular magnetic materials. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Synthesis of new chiral alkenyl Fischer carbene complexes

New chiral group 6 Fischer alkoxycarbene complexes 1 and 2 have been synthesized by condensation of enantiopure aldehydes 6 and 7, respectively, with methylcarbene complexes 5. The corresponding aminocarbene complexes 3 and 4 were accessible from 1 and 2 by methoxypyrrolidine exchange. The chromium carbene 1b underwent the benzannulation reaction with alkynes affording chiral substituted phenols 11.

First Enantioselective Total Synthesis of (8S,12R,15S)‐Prostaglandin J2.

AbstractFor Abstract see ChemInform Abstract in Full Text.

First enantioselective total synthesis of (8S,12R,15S)-prostaglandin J(2).

Enantioselective synthesis of natural PGJ(2) has been accomplished for the first time starting from the commercially available enantiopure aldehyde 7 in 10% overall yield. The key reaction was a novel prostaglandin class interconversion, i.e., an allylic 1,3-transposition across alcohol 9 derived from compound 14 in 73% overall yield. In principle, the unnatural enantiomer of PGJ(2) could be obtained starting from the commercially available enantiopure monobenzoate 7a following our strategy.

Addition of silanethiols to aldehydes and ketones: a simple route to homochiral α-siloxyalkanethiols

In the presence of imidazole as a catalyst, silanethiols R 3SiSH react by addition with aldehydes and with ketones that carry electron-withdrawing substituents to give α-siloxyalkanethiols R 1R 2C(SH)OSiR 3. Diastereoselective addition of a silanethiol to an enantiopure aldehyde or ketone provides a convenient route to a homochiral α-siloxyalkanethiol R 1R 2C*(SH)OSiR 3.

Enantioselective synthesis of a key intermediate aldehyde toward the polyene macrolide filipin III, based on a chiral oxazaborolidinone-promoted asymmetric aldol reaction

A versatile preparation of an enantiopure aldehyde useful for the asymmetric total synthesis of filipin III was developed using a chiral oxazaborolidinone-promoted asymmetric aldol reaction with a dithiolane silyl nucleophile. The sign and magnitude of the specific rotation of the aldehyde, (4 R,5 R)-2,2-dimethyl-5-formyl-4-pentyl-1,3-dioxane, were reconfirmed.

Origins of Stereocontrol in the [2 + 2] Cycloaddition between Achiral Ketenes and Chiral α-Alkoxy Aldehydes. A Pericyclic Alternative to the Aldol Reaction

Ab Initio calculations predict that the thermal [2 + 2] cycloaddition reaction between C2v-symmetric ketenes and enantiopure aldehydes takes place with high enough stereocontrol for preparative purposes. The sense of induction is predicted to be non-Felkin. It is also found that the [2 + 2] cycloaddition involving nonactivated ketenes is facilitated by using 5 M solutions of lithium perchlorate in diethyl ether. It is found that both the purely thermal and lithium-assisted [2 + 2] cycloadditions result in the same type of stereocontrol. This method constitutes a general route for the synthesis of homochiral 2-oxetanones and related compounds, thus providing a pericyclic alternative to the aldol reaction.

Stereoselective synthesis of novel cyclobutane dehydro amino acids from (+)-α-pinene

Several title compounds have been synthesized in good overall yields through highly stereoselective Wittig-Horner condensations of suitable phosphonates with enantiopure aldehydes easily obtained from α-pinene as chiral precursor. These products, presenting two asymmetric carbons, two or four prochiral centers, and appropriate chemical functions, are versatile precursors to a variety of cyclobutane amino acid derivatives.