Trimethylsilyloxy-1,3-butadienes, Diels-Alder

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. 

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]. 

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]. 

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. 

By allowing Cjq to react with 2-trimethylsilyloxy-1,3-butadiene in toluene at reflux [38, 94], another stable Diels-Alder adduct was obtained (Scheme 4.14). The ketone 93 is formed after hydrolysis of the uncharacterized intermediate silyl enol ether under flash chromatographic conditions. 

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. 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

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%. 

A clear two step formation of a pyrone by an enantioselective Mukaiyama-aldol and acid catalysed aldol dihydropyrone annulation using aliphatic and aromatic aldehydes and l-methoxy-3-trimethylsilyloxy-l,3-butadiene in the presence of a tryptophan-derived oxazaborolidine was described by Corey et al. [115]. The resulting pyrone which could be assigned as a formal Diels-Alder adduct was obtained with a 67-82% ee and 57 -100% yield. 

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... 

A select set of useful [4 + 2] cycloaddition reactions of simple 2-aza-1,3-butadienes have been detailed (Table 11), " and in most instances the 2-azadienes employed are substituted with strong electron-donating substituents responsible for enhancing its Diels-Alder reactivity toward electron-deficient dienophiles. The ease with which the l,3-bis(t-butyldimethylsilyloxy)-2-aza-1,3-butadienes may be prepared from imides, and the demonstrated facility with which they participate in HOMOdiene-controlled [4 + 2] cycloaddition reactions, may prove exceptionally useful their use constitutes the most general approach to implementing the 477 participation of 2-aza-1,3-butadienes (Scheme 12). With the recent introduction of a convenient preparation of 3-trimethylsilyloxy-2-aza-1,3-butadienes, their comparable synthetic utility may be anticipated. ... 

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... 

The octosyl acids are isolated from Streptomyces cacaoi they are part of a broader group of polyoxin antifungal nucleosides [349]. Danishefsky and co-workers [350] have reported a total synthesis of octosyl acid A featuring the hetero-Diels-Alder addition of ( )-l-methoxy-3-(trimethylsilyloxy)butadiene to a protected D-ribose-derived aldehyde. 

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... 

Kametani and co-workers have demonstrated what may prove to be the most convenient and effective approach to the utilization of l-aza-1,3-butadienes for intramolecular [4 + 2] cycloadditions.37 Treatment of a,j3-unsaturated enamides with trimethylsilylchloride-zinc chloride provides in situ generation of 2-trimethylsilyloxy-l-aza-1,3-butadienes which are capable of effective intramolecular [4 + 2] cycloaddition (Table 9-II, entries 12-14). Selected conditions have permitted this in situ generation and subsequent intramolecular Diels-Alder cycloaddition of 2-trimethy-lsilyloxy-l-aza-1,3-butadienes to be conducted at 25°C,37b and these observations have found application in the total syntheses of ( )-epilupinine and ( )-tylophorine [Eqs. (14) and (15)].37c,b... 

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. 

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