Diastereoselective Mukaiyama Research Articles

A Hetero-Diels−Alder Approach to Complex Pyrones: An Improved Synthesis of the Spongistatin AB Spiroketal

The conversion of a substituted dioxinone to a pyrone was used in an improved synthesis of the AB spiroketal subunit of the spongistatins. This transformation occurred via a hetero-Diels-Alder reaction of an acyl ketene with butyl vinyl ether. A double diastereoselective Mukaiyama aldol reaction is used to provide the hetero-Diels-Alder precursor.

Diastereoselective mukaiyama and free radical processes for the synthesis of polypropionate units.

[reaction: see text] Reported herein is the synthesis of 8 out of 16 polypropionates derived from our propionate units. A new strategy involving a stereoselective Mukaiyama aldol reaction followed by a stereoselective free-radical-based hydrogen transfer, both under Lewis acid control, is used. Of particular interest is the remarkable reactivity of (i-PrO)TiCl(3) in this context to give only the 3,4-anti bromoesters.

Variable strategy toward carbasugars and relatives. 6. Diastereoselective synthesis of 2-deoxy-2-amino-5a-carba-beta-L-mannopyranuronic acid and 2-deoxy-2-amino-5a-carba-beta-L-mannopyranose.

Efficient, total syntheses of novel 2-deoxy-2-amino-5a-carba-beta-L-mannopyranuronic acid (1) and 2-deoxy-2-amino-5a-carba-beta-L-mannopyranose (2), a positional stereoisomer of validamine, have been achieved in 28% and 24% overall yields and in 12 steps and 13 steps, respectively, from 2-[(tert-butyldimethylsilyl)oxy]furan (3) and (2S)-2,3-O-isopropylideneglyceraldehyde N-benzyl imine (4) via two highly diastereoselective Mukaiyama aldol-related chemical maneuvers. The strategy, which furnishes the targeted carbasugars in enantiopure forms, allows for complete control of the configuration at all five contiguous stereocenters of the targets by utilizing the sole element of chirality present in the aldimine progenitor 4.

Reexamination of CeCl3 and InCl3 as Activators in the Diastereoselective Mukaiyama Aldol Reaction in Aqueous Media.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reexamination of CeCl3 and InCl3 as activators in the diastereoselective Mukaiyama aldol reaction in aqueous media.

A search for suitable reaction conditions in Mukaiyama-type aldol condensations activated by CeCl(3) and InCl(3) revealed that the reaction proceeds best in i-PrOH/H(2)O (95:5). Contrary to literature precedent, no reaction was observed in pure water, and the encountered destruction of the starting silyl enol ether can be ascribed to initial hydrolysis of the Lewis acid. As anticipated from the dual parameter (pK(h), WERC value) characteristics of CeCl(3) and InCl(3), the former proved more efficient as Lewis acid-promoter, in terms of reaction speed and yield. Nevertheless, InCl(3) was a superior catalyst during evaluation of the diastereoselectivity of the process. In this regard, determination of diastereoselectivity as a function of time showed that the InCl(3)-catalyzed reaction is irreversible, whereas the CeCl(3)-catalyzed reaction is a reversible process. In both cases, formation of the syn product is kinetically preferred, although DeltaDeltaG(++)273K(InCl(3)) = 1.50 kcal/mol versus DeltaDeltaG(++)273K (CeCl(3)) = 0.38 kcal/mol. Molecular modeling (semiempirical PM3, ab initio HF/3-21G*, hybrid B3LYP/3-21G*, and B3LYP/LANL2DZ) of the diastereoselective aldol reaction promoted by InCl(3) supports a "closed", Zimmermann-Traxler transition state.

Asymmetric total synthesis of (-)-azaspirene, a novel angiogenesis inhibitor.

The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.

A straightforward strategy toward the construction of polypropionate frameworks, based on a sequence of diastereoselective Lewis acid-mediated aldol reaction and diastereoselective radical debromination reaction

An approach joining highly diastereoselective Mukaiyama aldol reaction (process A ) to the following radical debromination reaction (process B ) provides a reliable way to the stereoselective divergent synthesis of polypropionate frameworks. A practical and reliable synthesis of the complete set of propionate stereotetrads from enantiopure syn- and anti-2-methyl-3-methoxy-3-phenylpropanals was achieved by using the straightforward strategy.

ChemInform Abstract: Enantioselective and Diastereoselective Mukaiyama—Michael Reactions Catalyzed by Bis(oxazoline) Copper(II) Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by bis(oxazoline) copper(II) complexes.

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.

Total synthesis of the antiviral marine natural product (-)-hennoxazole A.

[structure:see text] The marine natural product hennoxazole A was synthesized by a convergent approach. The diastereoselective Mukaiyama aldol reaction with beta-alkoxy aldehyde was used to construct the tetrahydropyran segment, and the preparation of the nonconjugated triene moiety was accomplished via S(N)2 displacement of allylic bromide with vinyllithium and Takai's iodoolefination followed by palladium-catalyzed cross coupling with MeMgBr. The final steps involve an amide coupling using DEPC and oxazole synthesis via a oxidation/cyclodehydration process.

1,7-Asymmetric induction of chirality in a Mukaiyama aldol reaction using π-allyltricarbonyliron lactone complexes: highly diastereoselective synthesis of α-substituted β-hydroxy carbonyl compounds

Silyl enol ethers derived from ethyl ketone functionalised π-allyltricarbonyliron lactone complexes undergo highly diastereoselective Mukaiyama aldol reactions with a variety of achiral aldehydes, with control of both α- and β-stereogenic centres.

Total Synthesis of Dihydroclerodin from (R)-(−)-Carvone

The first total synthesis of the natural enantiomer of the insect-antifeedant dihydroclerodin (1) and lupulin C (40) has been achieved starting from (R)-(−)-carvone (2). In the applied strategy, the hexahydrofuro[2,3-b]furan moiety was introduced in an early stage of the synthesis. The correct configuration at C-9, C-11, C-13, and C-16 was established by application of a remarkably diastereoselective Mukaiyama reaction. The desired configuration at C-10 was obtained by catalytic reduction of the intermediate enone 21. After annulation of the second ring, the structural features at C-4, C-5, and C-6 were introduced. The successful finishing of the synthesis included a Chugaev elimination to give the exocyclic double bond at C-4 that is present in lupulin C. Oxidation of this double bond with m-CPBA afforded dihydroclerodin.

A New Magnesium-Catalyzed Doubly Diastereoselective anti-Aldol Reaction Leads to a Highly Efficient Process for the Total Synthesis of Lactacystin in Quantity

A new process is described for metal-catalyzed doubly diastereoselective Mukaiyama aldol coupling of a chiral tertiary α-amino aldehyde and an achiral silyl enol ether to form selectively an anti-aldol product. The metal requirement is strict, since of several salts tested only MgI2 functions as an effective catalyst. The MgI2-catalyzed aldol greatly facilitates the total synthesis of lactacystin (1) and the corresponding β-lactone (2), microbial products which are potent and selective inhibitors of proteasome function, cell cycle progression, and gene regulation. The method also allows the synthesis of analogues of 1 in which the 7β-methyl group of lactacystin is replaced by higher alkyl or aralkyl groups. Detailed experimental procedures are presented for the optimized synthesis of lactacystin on the scale required to meet the current needs of many hundreds of biological laboratories.

ChemInform Abstract: A Stereochemical Model for Merged 1,2‐ and 1,3‐Asymmetric Induction in Diastereoselective Mukaiyama Aldol Addition Reactions and Related Processes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Stereochemical Model for Merged 1,2- and 1,3-Asymmetric Induction in Diastereoselective Mukaiyama Aldol Addition Reactions and Related Processes

A systematic investigation of the direction and degree of stereoselectivity in aldol addition reactions is presented involving achiral unsubstituted metal enolate and enolsilane nucleophiles and chiral aldehydes. The BF3·OEt2 mediated Mukaiyama aldol reaction with α-unsubstituted, β-alkoxy aldehydes afforded good levels of 1,3-anti induction in the absence of internal aldehyde chelation. The level of 1,3-induction was found to be primarily dependent on the electrostatic nature of the aldehyde β-substituent. A revised model for 1,3-asymmetric induction is presented to account for these results based primarily on minimization of internal electrostatic and steric repulsion between the aldehyde carbonyl moiety and the β-substituents. A full conformational analysis, corroborated by semiempirical (AM1) calculations, is presented to support the proposed model. The merged impact of α and β aldehyde substituents was also systematically investigated, and an integrated 1,2- and 1,3-asymmetric induction model is proposed that incorporates the salient features of the Felkin−Anh and revised 1,3-model. In accordance with this integrated model, uniformly high levels of Felkin, 1,3-anti diastereofacial selectivity are observed in Mukaiyama aldol reactions with anti substituted α-methyl-β-alkoxy aldehydes, which contain stereocontrol elements that are in a stereoreinforcing relationship. In contrast, variable levels of aldehyde facial induction were observed in the corresponding reactions with syn substituted aldehyde substrates, which contain stereocontrol elements in a non-reinforcing relationship. The direction of aldehyde facial induction in Mukaiyama aldol additions to the syn substituted aldehydes was found to be primarily dependent on the size of the enolsilane, with the first known examples of anti-Felkin selective Mukaiyama aldol reactions observed under conditions known to preclude chelation for the addition of the enolsilane of acetone. We conclude that dominant 1,2-stereoinduction will be found in those reactions proceeding with the reactants in an antiperiplanar relationship, favored by sterically encumbered enolsilane substituents, while dominant 1,3-stereoinduction will be manifest from a synclinal transition state, preferred for less bulky enolsilane substituents. By inspection, the synclinal transition state may be destabilized by an increase in the steric bulk of the Lewis acid, and in accordance with this prediction the trityl perchlorate mediated enolsilane addition resulted in a dramatic reversal of facial selectivity relative to the BF3·OEt2 mediated reaction. These trends were also documented in the mechanistically related addition of allylstannanes to anti and syn disubstituted chiral aldehydes.