L-Methoxy-3-trimethylsilyloxy-1,3-butadiene

The hetero-Diels-Alder cyclization reaction of tra s-l-methoxy-3-trimethylsilyloxy-1,3-butadiene (Si) (= Danishefsky s diene) with benzaldehyde (S ) (Scheme 12.23) [217-221] is a promising reaction for evaluating the catalytic properties of Lewis acidic lanthanide centers, and has enormous potential for asymmetric synthesis of natural products (e.g., monosaccharides) [222-225]. 

Hybrid materials [Ln(fod) (THF)y] MCM-41.28o [Ln = Sc (18F), Y (19F) and La (26F)] and [Y(fod)3] MCM-41.28o (6) were used under standard conditions as catalysts for the Danishefsky transformation (Table 12.9). In these reactions 1.1 equivalents of benzaldehyde (Sj) were allowed to react with trans-l-methoxy-3-trimethylsilyloxy-1,3-butadiene (Si) in n-hexane at ambient temperature. The outcome of the reaction was highly dependent on the synthesis procedure used for the Ln-fod surface complexes. For materials [Ln(fod) ,(THF)y] MCM-41.28o. obtained by secondary ligand exchange from silylamide surface complexes 18,19 and 27 (via route C in Scheme 12.3 see also Table 12.3 and Scheme 12.8), the... 

Simple dienes react readily with good dienophiles in Diels-Alder reactions. Functionalized dienes are also important in organic synthesis. One example which illustrates the versatility of such reagents is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (.Danishefsky s diene) 1 Its Diels-Alder adducts are trimethylsilyl enol ethers which can be readily hydrolyzed to ketones. The /j-mcthoxy group is often eliminated during hydrolysis. 

CYCLOCONDENSATION (E,Z)-l-Methoxy-2-methyl-3-trimethylsilyloxy-l, 3-butadiene. (E)-l-Methoxy-3-trimethylsilyloxy-1,3-butadiene. 

Similarly, Keck [111] has used the Ti(0-i-Pr)4/BINOL complex (10 mol %) for the hetero Diels-Alder reaction of l-methoxy-3-trimethylsilyloxy-1,3-butadienes 2-10 and non-activated aldehydes. The lowest enantioselectivity was obtained with benzaldehyde and the best with phenylacetaldehyde and some aliphatic aldehydes to give the corresponding dihydropyrans with ee values ranging from 75 % up to 97%. 

One of the most popular dioxygenated dienes is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (109), the so-called Danishefsky diene (Scheme 30). The elegant application of this and related polyoxygen-ated dienes in synthesis was reviewed in 1981. ° [4 + 2] Cycloadditions of diene (109), wifo typical electron-poor dienophiles, display increased reactivity and legiochemical control owing to die synergism of die two oxygen atoms. Acidic hydrolysis of the initial cycloadducts readily affords cyclohexenones, phenols or cyclohexadienones (c/. Action 4.1.2, Schemes 12, 17,18 and 21). A pertinent example is the... 

Further extension of the reaction pool of Schilf bases 138 was achieved by their reaction with tran -l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene) to give 2-substituted 5,6-didehydro-piperidin-4-ones 164 [135,136] (Scheme 10.54). The reaction is considered to be a sequence of an initial Mannich reaction between the imine and the silyl enol ether, followed by an intramolecular Michael addition and subsequent elimination of methanol. If the reaction was terminated by dilute ammonium chloride solution, then the Mannich bases 163 could be isolated and further transformed to the dehydropiperidinones 164 by treatment with dilute hydrochloric acid. This result proved that the reaction pathway is not a concerted hetero Diels-Alder type process between the electron-rich diene and the activated imine. The use of hydrogen chloride as a terminating agent resulted in exclusive isolation of the piperidine derivatives 164 formed with... 

Among the more reactive and synthetically useful dienes are doubly and triply activated alkoxy- and amino-substituted dienes, such as ( )-l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene),( )-l-(dimethylamino)-3-(fert-butyldimethylsilyloxy)-1,3-butadiene (Rawal s diene)-, and 1,3-dimethoxy-l-(trimethylsilyloxy)-1,3-butadiene (Brassard s diene). As illustrated below, the cyclo-addition products arising from these dienes can either be hydrolyzed or treated with fluoride ion to remove the silyl group, which is followed by (3-elimination to provide conjugated cyclohexenones. 

Lewis acid catalysts increase the reactivity of dienophiles in Diels-Alder reactions by complexing to basic sites on the dienophile.10 The Lewis acid lowers the LUMO of the adjacent ir-system, which strengthens the overlap between the LUMO of the dienophile and the HOMO of the diene. In 1979 Scheeren reported that ZnCh catalyzes the cyclocondensation reaction of unactivated aldehydes with l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene.22 Experimental details of this reaction, however, were not fully documented. In 1982 Scheeren also reported the use of aluminum alkoxydichlorides as catalysts... 

Org. Synth. 6I IA1 (1983) l-methoxy-3-trimethylsilyloxy-1,3-butadiene is commercially available. 

Danishefsky and coworkers have used the racemic P-phenylsulfinyl-a,P-unsaturated ketone (160) as an a,P-ethynyl carbonyl synthetic equivalent and found that the phenylsulflnyl group did not compete with the carbonyl group in determining the regioselectivity of cycloaddition with the l-methoxy-3-trimethylsilyloxy-1,3-butadiene (161), now known as Danishefsky s diene [140] (Scheme 5.54). Loss of methanol and phenyl sulfenic acid from the initial cycloadduct (162) gave the aromatic product (163). 

The aldehyde group in tricarbonyl(Ti -2,4-hexadien-l-al)iron can undergo a hetero-Diels-Alder reaction with l-methoxy-3-trimethylsilyloxy-1,3-butadiene to give di-hydropyranones with moderate diastereoselectivity depending on the Lewis acid applied. ... 

The imino function adjacent to (diene)iron complexes can be employed in a hetero-Diels-Alder reaction with l-methoxy-3-trimethylsilyloxy-1,3-butadiene. This leads to tetrahydropyridinones pendent to the (diene)iron system. The biologically active piperidine alkaloid SS20846 A has been synthesized using this procedure. Ketones adjacent to the tricarbonyl(diene)iron unit can be reacted with nucleophiles using the stereodirecting effect of the tricarbonyliron moiety. Spiroketals are formed in good diastereoselectivity from appropriately functionalized 1- and 2-sulfinyl l,3-dien-5-ones under the stereodirecting influence of the tricarbonyliron moiety (Scheme 4-139). ... 

Dichlorobis(diisopropoxy)titanium(IV). Titanium(IV) chloride. Zinc iodide. DIELS-ALDER REACTIONS 2-Acetoxy-I-methoxy-3-trimethylsilyloxy-1,3-butadiene. 4-Acetoxy-1 -trimethylsilyl-1,3-butadiene. Benzyl irans-l,3-butadiene-l-carbamate. 1,3-Bis(/-butyldimethylsilyloxy)-2-aza-1,3-diene. 2,3-Bis(trimethylsilyl)methyl-1.3-buladiene (10-1,3-Dimethoxybutadiene 4-I)iniethyhnnino 1,1,2... 

Danishefsky s diene l-methoxy-3-trimethylsilyloxy-l,3-butadiene DBN 1,5-diazobicyclo [4.3.0]non-5-ene... 

The reaction of N-(terf-butoxycarbonyl)leucinal 2-41 a by Danishefsky et al. with l-methoxy-3-trimethylsilyloxy-l,3-butadiene 2-10 gave the pyrones 2-42 and 2-43 with an induced diastereoselectivity of 9 1 in favour of the syn-com-pound in the presence of Eu(hfc)3 [96]. Later Garner [97] used a N-Boc-serine derived aldehyde 2-41 b and Danishefsky s diene 2-10. In both cases a chelation-control forming a complex between the nitrogen and the oxygen could explain the obtained selectivity. In the presence of HMPA chelation is minimized to give a higher extent of the anfi-product 2-43 (Fig. 2-12) [97]. 

The 1-azadiene and the dienophilic character of 2-alkenyl-5,6-dihydro-4//-l,3,4-oxadiazines (150 Section 6.17.6.2) have been explored (Scheme 21) <93TL457>. Attempts to effect cycloaddition with DMAD, dimethyl fumarate, and acrylonitrile failed, whereas with maleic anhydride and A-methylmaleimide unexpected noncyclic adducts (e.g. 151) are obtained. The alkenyl oxadiazines also fail to give cycloadducts with l-methoxy-3-trimethylsilyloxy-l,3-butadiene with or without the presence of a Lewis acid catalyst. However, with methyl penta-2,4-dienoate mixtures of diastereo-isomeric products (e.g. 152) are formed, albeit slowly, by [4 + 2] cycloaddition at the alkenyl side chain, rather than at the C2—N3 imine bond. 

There have been few mechanistic studies of Lewis acid-catalyzed cycloaddition reactions with carbonyl compounds. Danishefsky et ah, for example, concluded that the reaction of benzaldehyde 1 with trans-l-methoxy-3-(trimethylsilyloxy)-l,3-di-methyl-1,3-butadiene (Danishefsky s diene) 2 in the presence of BF3 as the catalyst proceeds via a stepwise mechanism, whereas a concerted reaction occurs when ZnCl2 or lanthanides are used as catalysts (Scheme 4.3) [7]. The evidence of a change in the diastereochemistry of the reaction is that trans-3 is the major cycloaddition product in the Bp3-catalyzed reaction, whereas cis-3 is the major product in, for example, the ZnCl2-catalyzed reaction - the latter resulting from exo addition (Scheme 4.3). 

Node and co-workers have found that the Diels-Alder reaction of nitroalkenes v/ith 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s dienesi exhibit abnormal exo-se-lecdvity Electrostadc repulsion between the nitro and the silyloxy group of the diene induces this abnormal exc-selecdvity (Tq 8 10 This selecdve reacdon has been used for the asymmetric synthesis of various naniral products as shovm in Scheme 8 6... 

Ln = Sc, Y, La), and have been tested as heterogeneous catalyst in the Diels-Alder cyclization of terH-methoxy-3-trimethylsilyloxy-l,3-butadiene with benzaldehyde (Danishefsky transformation of 1,3-dienes), and proved active [51]. The surface yttrium bis-dionate has also been synthesized directly from the molecular precursor [Y( Bu-COCHCO-"C3F7)3] by reaction with MCM-41 surface silanols [51]. 

Diels-Alder reactions.1 This highly substituted silyloxydiene is comparable to 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (6, 370 9, 303-304) in reactivity in Diels-Alder reactions. 

The application of Lewis acids, such as the europium salt Eu(fod)3, in [4+2] cycloadditions of carbonyl compounds (e.g. glyoxylates and aldehydes) with 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene) has been intensively examined by Danishefsky et al. and employed in natural product synthesis. ... 

We assumed that electron-rich dienes should allow for aza-Diels-Alde reactions with the imines 2 5 at lower temperature and with highei stereoselection. Therefore, the aldimine 2 9 generated from the galactosylamine 24 and pyridine-3-aldehyde, was treated with l-methoxy-3-trimethylsilyloxy-butadiene (Danishefsky s diene ). Two equivalents of zinc chloride in tetrahydrofuran must be applied for the reaction to proceed. The first obviously is coordinated to the pyridine nitrogen and, thus, completely inactivated. The second initiates the cyclocondensation to give the N-galactosyl-dehydro-piperidinone derivative 30 in high yield and with a diastereoselectivity of more than 20 1 (eq. 14) 1. 

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