Dihydropyran asymmetric reaction

A number of chiral 5,6-dihydropyran-2-ones and tetrahydropyran-2-ones have been prepared from key intermediates generated through an asymmetric reaction belonging to one of the following types [6] ... 

In this section, we will discuss a few other types of asymmetric reactions that have been used for the synthesis of 5,6-dihydropyran-2-ones in an enantioenriched form. One example is the recent synthesis of a pyrone isolated from R. crassifolia where organocatalytic a-hydroxylation of aldehydes via a-aminooxylation is used (Scheme 2.24) [39b]. Treatment of 5-phenyUiexanal with nitrosobenzene and l-proline at room temperature gave a-aminooxyhexanal 125, which was treated in situ... 

At low temperatures, the Zn enolate derived from dimethyl 3-methylpent-2-endioate 39 reacts with aldehydes in a one-pot aldolisation and cyclisation to yield the syn-dihydropyran-2-one 40. At the higher temperatures necessary to achieve reaction with a-aminoaldehydes, the anri-products predominate indicating thermodynamic control (Scheme 22) <99T7847>. An aldol condensation features in the asymmetric synthesis of phomalactone. The key step is the reaction of the enolate of the vinylogous urethane 41 with crotonaldehyde which occurs with 99% syn-diastereoselectivity and in 99% ee (Scheme 23) <99TL1257>. 

Diastereo- and enantio-selective cascade of Michael addition and lactonization between various silyl enolates derived from phenyl carboxylates and -unsaturated ketones were successfully carried out by using an efficient organic catalyst, a cinchoni- dine-derived chiral quaternary ammonium phenoxide. In this asymmetric domino reaction, the corresponding tnms-3,4-dihydropyran-2-oncs were obtained in high yields with almost complete diastereoselectivities and good to excellent enantioselectivities.161... 

Another landmark development in the area of hDA chemistry is the emergence of the tridentate chromium complexes 194 that can catalyze the reaction of njl-unsaturatcd aldehydes with vinyl ethers to afford dihydropyrans with high diastereo- and enantioselectivity (Equation 91) <2002AGE3059>. The same catalytic system can be used for the asymmetric synthesis of the 3,4-dihydropyran 195 from 3-boronoacrolein pinacolate and ethyl vinyl ether in quantitative yield (Equation 92) <2003JA9308, 2005JA1628>. 

Synthesis of a key 3,4-dihydropyran 196 during synthetic studies towards reveromycin B is achieved using an asymmetric hDA reaction. No chiral Lewis acid catalysts or auxiliaries are necessary as the stereochemistry at the spirocentre is controlled by the anomeric effect (Equation 93) <1997JOCl 196>. 

A catalytic asymmetric vinylogous Mukaiyama reaction between silyl dienolate 896 and aliphatic ketone 897 provides the 5,6-dihydropyran-2-one 898, a key intermediate during a formal synthesis of enantiopure taurospongin A (Equation 361) <2005JA7288>. 

The use of the zinc complex of the BINOL ligand 946 in the hDA reaction between Danishefsky s diene 947 and aldehydes proceeds in excellent yield and enantioselectivity to afford dihydropyran-4-ones 948 (Equation 370, Table 45) <2002OL4349>. An asymmetric diethyl zinc addition can occur in tandem with the cycloaddition reaction between Danishefsky s diene 947 and isophthalaldehyde using a related catalyst 949 (Equation 371) <20030L1091, 2005T9465>. 

Diazo-3,6-dihydropyran-2-one 21 is a stable vinylcarbene precursor. Its reaction with 1,4-cyclohexadiene is highly dependent on the chiral Rh catalyst used but results in both C-H insertion and cyclopropanation. Asymmetric cyclopropanation also occurs with various alkenes and reduction of the products provides a route to cycloheptadienes <06JA16038>. 

Hetero- Diels-Alder reactions that proceed with good to excellent asymmetric induction are well known. " Chiral 1-aza-dienes have been developed as substrates, for example. " Chiral catalysts have been developed. " Conjugated aldehydes react with vinyl ethers, with a chiral chromium catalyst, in an inverse electron demand cycloaddition that give a dihydropyran with good... 

The same group also studied the BF3 OEt2 catalyzed inverse reaction between chiral 2-oxybenzaldehyde 148 and Danishefsky s diene, showing a notable example of 1,5-asymmetric induction [110] (Scheme 10.48). After acidic workup, a 9 1 mixture of the 2-aryl-2,3-dihydropyran-4-ones 149S and 149/f was isolated obviously formed via an aldoTcyclocondensa-tion sequence. 

This process (hetero Diels-Alder reaction leading to a dihydropyran system) may be also conducted in an asymmetric version application of chiral transition-metal catalysts based on BINOL, BDMAP, bisoxazolines, etc. provides adducts in very high optical purity (ee up to 99%) [1,6], In a series of papers Jurczak reported recently a highly enantioselective cycloaddition of 1-methoxy-1,3-butadiene and butyl glyoxylate catalyzed with chiral salen complexes [21],... 

A library of chiral dihydropyrans (226) [241] was synthesized using asymmetric hetero-Diels-Alder reactions (HAD) on polymer-bound enol ethers (221) and a, 3-unsaturated oxalyl esters (222). A chiral Lewis acidic Cu -bisoxazoline complex was used because of its high efficiency, the high predictability of the reaction outcome, and its broad substrate tolerance [280]. Enol ethers were used as alkene components bearing a hydroxy function for attachment to the resin via a silyl linkage (Scheme 49). The diene components carried allyl-ester groups, which could be readily displaced by amino functions in subsequent steps of the combinatorial synthesis. 

New work on the asymmetric hetero DA reaction as a route to 2,3-dihydropyran-4-ones includes the use of axially chiral biaryl-based diols <05JA1336> and chiral Bronsted acids <05TL6355> which work through hydrogen bonding. Polymer-bound Danishefsky s diene derived from acetoacetate has been used in the hetero DA reaction with aldehydes. With a chiral BINOL-Ti(IV) complex, good yields of 2-aryl-5-methoxycarbonyl-5,6-dihydropyran-... 

Based on their early study in the enantioselective carbonyl-ene reaction [23], Nakai, Mikami, and Terada have found that the asymmetric hetero-Diels-Alder reaction of prochiral glyoxylate with methoxydiene can be catalyzed by the chiral titanium complex, producing the a s-dihydropyran carboxylate as a major product in high enantiomeric purity (Scheme 11) [24]. 

Asymmetric Diels-Alder reaction and its applications based on catalysis by bis(oxa-zoline)copper(II) complexes have been published in full details. This method has been further extended to the synthesis of 2,3-dihydropyran-6-ylphosphonates, 4-aminodihy-dropyrans, and piperidones. Note that both epimeric amines are accessible by merely changing the diene substrate, that is, ( )- versus (Z)-configuration. Diazolidi-none 75 serves as a chiral catalyst that also activates enals (actual dienophiles being the iminium ions)." ... 

Chiral boron complexes derived from tartaric acid derivatives and from P-aminoalcohols act as mild Lewis acids and asymmetric catalysts for the reaction of aldehydes (94T979) and methyl glyoxalate (94CC1563) with Danishefsky dienes. The resulting 2,3-dihydropyran-4-ones are obtained in high optic purity. 

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