Double Asymmetric Reactions Research Articles

ChemInform Abstract: (Diisopinocampheyl)borane‐Mediated Reductive Aldol Reactions of Acrylate Esters: Enantioselective Synthesis of anti‐Aldols.

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters 4 is described. Isomerization of the kinetically formed Z(O)-enolborinate 5Z to the thermodynamic E(O)-enolborinate 5E via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to anti-α-methyl-β-hydroxy esters 9 or 10 with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of 5E with several chiral aldehydes are also presented.

(Diisopinocampheyl)borane-Mediated Reductive Aldol Reactions of Acrylate Esters: Enantioselective Synthesis ofAnti-Aldols

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters 4 is described. Isomerization of the kinetically formed Z(O)-enolborinate 5Z to the thermodynamic E(O)-enolborinate 5E via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to anti-α-methyl-β-hydroxy esters 9 or 10 with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of 5E with several chiral aldehydes are also presented.

Regiodivergent Epoxide Opening: A Concept in Stereoselective Catalysis beyond Classical Kinetic Resolutions and Desymmetrizations

An approach to highly regiodivergent epoxide openings (REOs) is presented. The very popular kinetic resolutions of epoxides and openings of meso-epoxides constitute subclasses of such REOs. REOs are attractive for parallel resolutions, double asymmetric reactions of enantiomerically enriched epoxides, and for semisynthetic applications in the functionalization of natural products. They have been notoriously difficult to realize by means of SN2 mechanisms. Our titanocene-catalyzed radical REO addresses this issue by decoupling epoxide opening and radical trapping and is firmly based on a mechanistic study of the reductive epoxide opening.

Stereoselective Titanium‐Mediated syn‐Aldol Reaction from a Lactate‐Derived Chiral Ethyl Ketone.

Abstract Stereoselectivity of the titanium-mediated aldol process based on ( S )-2-benzyloxy-3-pentanone, 1 , is dramatically modified by the presence of a Lewis acid. Among the Lewis acids surveyed, TiCl 4 has given access to the corresponding 2,4- anti -4,5- syn aldol adducts with the highest diastereomeric ratios. The excellent stereocontrol exerted by the aforementioned ketone has been demonstrated in double asymmetric reactions involving chiral α-methyl-β-OTBDPS aldehydes.

Stereoselective titanium-mediated syn-aldol reaction from a lactate-derived chiral ethyl ketone

Stereoselectivity of the titanium-mediated aldol process based on (S)-2-benzyloxy-3-pentanone, 1, is dramatically modified by the presence of a Lewis acid. Among the Lewis acids surveyed, TiCl4 has given access to the corresponding 2,4-anti-4,5-syn aldol adducts with the highest diastereomeric ratios. The excellent stereocontrol exerted by the aforementioned ketone has been demonstrated in double asymmetric reactions involving chiral α-methyl-β-OTBDPS aldehydes.

Synthesis of the C(21)-C(26) fragment of superstolide A: concerning the stereochemistry of (E)-crotylboration reactions of alaninal derivatives.

A stereoselective synthesis of the C(21)-C(26) fragment of superstolide A has been completed. The absolute and relative stereochemistry of intermediate 14 has been conclusively proven by NMR and X-ray diffraction methods. In the course of this work, it was found that the stereochemistry of 3 had been misassigned in our previously reported synthesis of the C(18)-C(26) segment. This error stems from the unexpected diastereoselectivity in the double asymmetric reaction of N-acetyl-d-alaninal 1 and the tartrate ester modified (E)-crotylboronate (R,R)-2.

Diastereoselective Chloroallylboration of α-Chiral Aldehydes

Double asymmetric reaction of chiral (Z)-(γ-chloroallyl)borane, 2, with α-chiral aldehydes (3−7) provide a new practical method for the generation of 2,3-syn-3,4-anti and 2,3-syn-3,4-syn chiral vinylchlorohydrins (8−17) and vinyl epoxides (18−27). Both enantiomers of 2 exhibited excellent diatereoselectivity (≥90 de) for matched cases. The mismatched cases yielded moderate to good diastereoselectivity.

Total synthesis of (−)-epothilone B

The sixteen-membered ring macrolide (–)-epothilone B 1 has been synthesized by a route which features stereospecific methylation of an (E)-γ,δ-epoxy acrylate, the use of a double asymmetric reaction employing (R,R)-diisopropyltartrate and (E)-crotylboronate, and ring closure by means of an olefin metathesis reaction.

4,5-Diisopropyl-B-[(E)-[(3‘-menthofuryl)dimethylsilyl]allyl]-1,3,2- dioxaborolane, an Improved Chiral Reagent for the Anti α-Hydroxyallylation of Aldehydes: Application to the Enantioselective Synthesis of (−)-Swainsonine

Diisopropyl tartrate-modified (E)-[γ-(furyldimethylsilyl)allyl]boronates 10 and 11 were designed for the enantioselective synthesis of substituted anti-3,4-dihydroxy-1-butenes 9 via the anti-α-hydroxyallylation of aldehydes. The reactions of aldehydes with 10 and 11 provided furyldimethylsilyl-substituted anti-1,2-silanols 12 and 13 with good enantioselectivity (74−82% ee), and the silanols were oxidized to the corresponding anti-1,2-diols 9 by a modified Fleming−Tamao oxidation protocol. The high reactivity of the (menthofuryl)silane unit toward electrophilic substitution allowed complete protodesilylation of menthofuryl-substituted silanols 13 and subsequent oxidation to diols 9 in a one-pot operation without competing protodesilylation of the allylsilane unit. However, a two-step protocol was required for the protodesilylation−oxidation of the less reactive 2-(5-methyl)furyl-substituted silanols 12. Reagents 10 and 11 exhibited similar diastereoselectivity in double asymmetric reactions with three chiral aldehydes 23−25 (80 to >92% de, with the exception of the mismatched reactions with aldehyde 25, which were essentially unselective). However, [[[2-(5-methylfuryl)]dimethylsilyl]allyl]boronate 10 could only be synthesized in ≤15% yield, and oxidations of the 2-(5-methylfuryl)-substituted silanols 12 were lower-yielding than oxidations of the corresponding menthofuryl-substituted silanols 13. Thus, diisopropyl tartrate-modified (E)-[γ-[(menthofuryl)dimethylsilyl]allyl]boronate 11 proved to be the more useful of the two reagents. As a demonstration of the utility of 11 in the synthesis of polyhydroxylated natural products, this new reagent was used in a brief and highly stereoselective synthesis of the naturally occurring alkaloid (−)-swainsonine (42).

Synthesis of the C(3)C(15) segment of rutamycin B via a C(8)C(9) fragment assembly aldol reaction: Metal dependence of the aldehyde and enolate diastereofacial selectivities

The diastereofacial selectivities of aldehyde 2b and ketone 3 are metal dependent, and their fragment assembly aldol coupling is a matched double asymmetric reaction when a chlorotitanium enolate is used.

Diisopropyl tartrate modified (E)-γ-[(cyclohexyloxy)dimethylsilyl]- and (E)-γ-(dimethylphenylsilyl)allylboronates: Chiral Reagents for the Enantio- and Diastereoselective synthesis of anti 1,2-diols and 2-butene-1,4-diols via the formal α- and γ-hydroxyallylation of aldehydes

Enantioselective synthesis of 4-substituted (E)-2-butene-1,4-diols and anti 1,2-diols are described. Highly diastereoselective reactions of aldehydes and the chiral PhMe 2Si- and (C 6H 11O)Me 2Si- substituted allylboronates 25 and 26 provide anti homoallylic 29 and 50, respectively. Epoxidation of 29 with dimethyl dioxirane followed by acid catalyzed Petersen rearrangement of the intermediate epoxysilanols provides butene-1,4-diols 27 with excellent enantioselectivity (81–87% e.e.). Tamao oxidation of 50 provides anti diols 22 (64–72% e.e). These procedures give excellent results especially in matched double asymmetric reactions with a range of oxygenated, chiral aldehydes (Figures 1 and 2). These methods promise to find application in diastereoselective syntheses of carbohydrates from acyclic precursors.

ChemInform Abstract: Acyclic Diastereoselective Synthesis Using Tartrate Ester Modified Crotylboronates. Double Asymmetric Reactions with α‐Methyl Chiral Aldehydes and Synthesis of the C(19)‐C(29) Segment of Rifamycin S.

AbstractThe enantiomeric title crotylboronates (Ia) and (Ib) react stereoselectively with chiral aldehydes, e.g. (II) and (V), to give the products (III) and (VI), resp., with anti and syn relationship between the branching methyl groups.

Acyclic diastereoselective synthesis using tartrate ester-modified crotylboronates. Double asymmetric reactions with .alpha.-methyl chiral aldehydes and synthesis of the C(19)-C(29) segment of rifamycin S

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcyclic diastereoselective synthesis using tartrate ester-modified crotylboronates. Double asymmetric reactions with .alpha.-methyl chiral aldehydes and synthesis of the C(19)-C(29) segment of rifamycin SWilliam R. Roush, Alan D. Palkowitz, and Kaori AndoCite this: J. Am. Chem. Soc. 1990, 112, 17, 6348–6359Publication Date (Print):August 1, 1990Publication History Published online1 May 2002Published inissue 1 August 1990https://doi.org/10.1021/ja00173a024RIGHTS & PERMISSIONSArticle Views2656Altmetric-Citations245LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts Get e-Alerts

Asymmetric synthesis using tartrate ester modified allylboronates. 2. Single and double asymmetric reactions with alkoxy-substituted aldehydes

Les substituants α- et β-alkoxy aldehydes de conformation non restreinte ont un effet negatif sur la stereoselectivite des allylborations asymetriques, contrairement aux formes chirales contenant un groupement alkoxy a conformation restreinte. Presentation d'un modele presentant «l'effet alkoxy»

Diisopropyl tartrate modified (E)-γ-[(cyclohexyloxy)dimethylsilyl-allylboronate, a chiral reagent for the stereoselective synthesis of anti 1,2-diols via the formal α-hydroxyallylation of aldehydes

An enantioselective synthesis of anti 1,2-diols via the reactions of aldehydes and the tartrate ester modified γ(alkoxysilyl)allylboronate 2 has been developed. This method is most effective in double asymmetric reactions with chiral aldehydes.

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

AbstractThis account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions‐the aldol, Diels‐Alder, catalytic hydrogenation, and epoxidation‐it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.