Diels-Alder reactions 2- trimethylsilyloxy-1,3-butadiene

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... 

Ohfune and coworkers78 used Diels-Alder reactions between 2-trimethylsilyloxy-l,3-butadiene (63) and acrylate esters 64 to synthesize constrained L-glutamates which they intended to use for the determination of the conformational requirements of glutamate receptors. The reactions between 63 and acrylate esters 64a and 64b did not proceed. Changing the ethyl and methyl ester moieties into more electron-deficient ester moieties, however, led to formation of Diels-Alder adducts, the yields being moderate to good. In nearly all cases, the cycloadducts were obtained as single diastereomers, which is indicative of a complete facial selectivity (equation 22, Table 1). Other dienes, e.g. cyclopentadiene and isoprene, also showed a markedly enhanced reactivity toward acrylate 64g in comparison with acrylate 64a. 

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. 

Butadienes substituted with alkoxy groups in the 2-position, e.g., 2-ethoxy-1,3-butadiene,6 have been prepared from methyl vinyl ketone, but they required several conversions and a tedious spinning-band distillation to purify the product. This slight modification of the House procedure has been used to conveniently prepare 2-trimethylsilyloxy-l,3-butadiene from the readily available methyl vinyl ketone. This one-step procedure has provided large amounts of a new and reactive diene for Diels-Alder reactions, as illustrated in Table I. 

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. 

Diels-Alder reactions with aldehydes.2 This catalyst is superior to zinc chloride3 for promoting [4 + 2]cycloaddition of aldehydes with l-alkoxy-3-trimethylsilyloxy-1,3-butadienes to form 2,3-dihydro-4//-pyrane-4-ones. The catalyst prepared from bornyl alcohol is somewhat more effective than similar catalysts from simple alcohols, and may be of value for asymmetric induction. 

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... 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

The Diels-Alder reactions of a-aminonitriles with l-methoxy-3-trimethylsilyloxy-l,3-butadiene in the presence of a Lewis acid gave, after acidic hydrolysis, cyanohydroisoquinolines 33 <1998TL5417>. When no Lewis acid was used, the reaction did not proceed apparently showing that the 2,3-dihydropyridinium salt is the active species and that cyanide ion is reintroduced after the Diels-Alder reaction (Scheme 7). 

Butadienes with alkyl substituents in the 2-position favor the formation of the so-called para-products (Figure 15.25, X = H) in their reactions with acceptor-substituted dienophiles. The so-called mefa-product is formed in smaller amounts. This regioselectivity increases if the dienophile carries two geminal acceptors (Figure 15.25, X = CN). 2-Phenyl-1,3-butadiene exhibits a higher para -selectivity in its reactions with every unsymmetrical dienophile than any 2-alkyl-1,3-butadiene does. This is even more true for 2-methoxy- 1,3-butadiene and 2-(trimethylsilyloxy)-l,3-butadiene. Equation 15.2, which describes the stabilization of the transition states of Diels-Alder reactions in terms of the frontier orbitals, also explains the para "/"meta "-orientation. The numerators of both fractions assume different values depending on the orientation, while the denominators are independent of the orientation. 

Steric control of the Diels-Alder reaction of the enone 56 has been reported (82H2053). The ene adduct 57 (4.5%) was obtained in a reaction with 1,3-bis(trimethylsilyloxy)butadiene at 180°C, together with the main product 58 (39.5%) resulting from an ene addition. Under the same conditions, the analogous indolizidine derivative 59 gave only ene adducts. 

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%. 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

DIELS-ALDER REACTIONS 3-Acetyl-4-oxazoline-2-one. 1,3-Bis(trimethylsilyl-oxy)-l,3-butadiene. 1-Chloro-l-di-methylaminoisoprene. 1,3-Dihydroiso-thianaphthene-2,2-dioxide. 4,6-Di-methoxy-2-pyrone. Furane. trans -Methoxy-3-trimethylsilyloxy-l,3-butadiene. Trichloroethyl trans-1,3-butadiene-1-carbamate. Trichloro-1,2,4-triazine. 

Monoalkoxy- and trimethylsilyloxy-l,3 butadienes are electron-rich dienes and have been extensively used in Diels-Alder reactions with electron-poor dienophiles, as already shown in Section 4.1.2 (Schemes 8 and 25). A very recent example is the synthesis of the labdane diterpenoid ( )-erigerol (105), which centers on the key step (102) + (103) (104) (Scheme 28). Diene (102) features, apart firom the... 

Dienes substituted with RO and R2N groups (e.g., Danishefsky s diene, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene) are particularly good substrates for Diels-Alder reactions, but alkyl-substituted dienes and even butadiene itself are common substrates. Benzene rings are very poor dienes in Diels-Alder reactions,... 

In the conrse of their research about drugs with oncologic activity, Martinez and Iglesias examined the Diels-Alder reaction between 1-trimethylsilyloxy-l,3-butadiene (50) and nitroalkene 51 which afforded, after hydrolytic work-up, a mixture of two regioi-someric pairs of endo/exo isomers 52/53 and 54/55 in a ratio of 52/53/54/55 = 78 17 ... 

Lewis acid catalysts increase the reactivity of dienophiles in Diels-Alder reactions by complexing to basic sites on the dienophile. ° 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)-l,3-butadiene. Experimental details of this reaction, however, were not fully documented. In 1982 Scheeren also reported the use of aluminum alkoxydichlorides as catalysts... 

The synthesis of Ilia starts from the unknown 4-nitrocyclohexanone, which was achieved by a Diels-Alder reaction between nitroethylene and 2-(trimethylsilyloxy)-l,3-butadiene, and following the sequence depicted in Scheme 34, vinyl bromide 112a was obtained. This amino-tethered ketone vinyl halide was treated with 0.2 equiv of Pd(PPh3)4 and 1.5 equiv of KOt-Bu at reflux temperature (THF) for 30 min to give the azatricyclic compound 111a in 54% yield. 

In a synthesis of the tricychc skeleton of FR901483 (45), Bonjoch and Sole reported a TMG (3) promoted conjugate addition reaction of nitroalkane to methyl acrylate. Reaction of methyl acrylate (40) and nitro acetal 41 [9,10], obtained from Diels-Alder reaction between nitroethylene and 2-(trimethylsilyloxy)-l,3-butadiene, gave nitro ester 42 in 71% yield. The ester 42 was further converted to the spiro compound 43, and a palladium promoted cyclization reaction led to the azatricyclic skeleton 44 (Scheme 7.7). 

DIELS-ALDER CATALYSTS Aluminum chloride. Boron trifluoiide etherate. DIELS-ALDER REACTIONS 2,3-Bis-(trimethylsilyloxy)-l,3-butadiene. 

DIELS-ALDER REACTIONS l,3-Bis(trimethylsilyIoxy)-l,3-butadiene. trans, rnms-1,4-Diacetoxybutadiene. 1,2-Dicyanocyclobulene. Ethyl /fans-1,3-butadiene-I-carbonate. Furane. 2-(2-MethoxyFallylidene-l,3-dithiane. 2-Methoxy-3-phenyIthiobuta-l,3-diene. l-Methoxy-3-trimcthylsilyloxy-l,3-butadiene. Sulfur dioxide. 1-Trimethylsily 1-1,3-butadiene. 2-Trimethylsilyloxy-l, 3-butadiene. 

In 1995, Katsuki and Yamashita [11a] found that Mg-salen complex and Co- or Cr-salen complexes served as Lewis acid catalysts for asymmetric Diels-Alder reactions and hetero Diels-Alder (HDA) reaction of Danishefsky s diene (l-methoxy-3-trimethylsilyloxy-l,3-butadiene) with aldehydes. Later on, they found that second-generation (R,S)-(ON )Ru-salen complex bearing chiral binaphthyl and ethylenediamine units also served as a catalyst for asymmetric HDA reaction between Danishefsky s diene and benzaldehyde [llbj. Recently, in 2001 they reported that (R,S)-Ru(II)-salen complex served as a good catalyst for... 

Although commercially available, 1-trimethylsilyloxy-1,3-butadiene (1) can be easily prepared by silylation of crotonaldehyde. It has often been used as a reactive diene in Diels-Alder reactions. For example, reaction with dimethyl acetylenedicarboxylate (2) affords the cyclohexadiene diester (3) in 68% yield. This initial Diels-Alder adduct can be converted into two different aromatic products by the proper choice of conditions namely, thermal elimination affords the phthalate (4), while oxidation produces the phenol (5), hoth in good yield (eq 1). Reaction with methyl 3-nitroacrylate (6) followed hy hydrolysis of the initial adduct (7) and elimination of the -nitro group leads to the cyclohexadienol (8) (eq 2). Many other Diels-Alder reactions of this type have been carried out using (1), as shown in Table 1. In general, the endo adduct is favored, especially at lower temperatures. 

Diels-Alder Reactions. Although commercially available, 2-trimethylsilyloxy-1,3-butadiene (1) can be easily prepared by sily-lation of methyl vinyl ketone. It has been often used as a reactive diene in Diels-Alder reactions. In nearly all cases with a strongly activated dienophile, the trimethylsilyloxy group ends up 1,4 to the activating group in the adduct. Several representative examples are shown in Table 1. The initial Diels-Alder adduct is a... 

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