Trimethylsilyloxy-1,3-dienes

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

The cycloaddition reaction is applicable to various derivatives of 3-trimethylsilyloxy-1,3-diene, including 1-alkyl derivatives, thus providing stereoselective routes to various derivatives of 4-pyranone. ... 

Anthracyclines Benzyltrimethylammonium hydroxide. Chromium carbene complexes. l-Methoxy-3-trimethylsilyloxy-1,3-dienes. 

Rubottom, G. M., Gruber, J. M. m-Chloroperbenzoic acid oxidation of 2-trimethylsilyloxy-1,3-dienes. Synthesis of a-hydroxy and a-acetoxy enones. J. Org. Chem. 1978, 43, 1599-1602. 

Compared to cyclic dienes, acyclic dienes are less commonly used in aryne Diels-Alder reactions, although one example has been reported by Sarandeses et al. in the synthesis of helicenes (Scheme 12.48) [89]. Functionalized [4]/[5]heli-cenes 166 have been synthesized in five steps starting from 164, using a synthetic approach based on a Diels-Alder reaction between the l,3-bis(trimethylsilyloxy)-1,3-dienes 165 and benzyne [90]. 

Ibuka, T. Mori, Y. Inubushi, Y. "A New Stereoselective Synthesis of c//-Pumiliotoxin C Usrg Novel 1,3-Bis(trimethylsilyloxy)-1,3-dienes" Tatrahedron Lett. 1976,3169-3172. 

Likewise, addition of enol silyl ethers such as 980 to the intermediate 977 a furnish the 5-trimethylsilylmethylisoxazolidine 981 in 61% yield and 15% isoxazoline 982 [73, 74] whereas addition of 2-trimethylsilyloxyfuran 827 to 977 a affords, via the intermediates 983, on work-up with CF3CO2H, 96% yield of a mixture of lactones 984 and 985 [75] (Scheme 7.23). More recently it has also been reported that Danishefsky (trimethylsilyloxy)dienes add to intermediates such as 977 to give the corresponding products [76]. 

On transforming the cyclopentenone 1431 into the trimethylsilyloxy diene 1432 the ensuing Diels-Alder cyclization gives rise to 69% tricychc compound 1433 [10] (Scheme 9.8). For Diels-Alder-reactions of thioaldehydes, selenoaldehydes, or unsaturated nitroso compounds with cyclopentadiene, see the reactions of 602 to 603 and of 605 to 606 in Scheme 5.48 and of 1092 to 1093 in Scheme 7.43. For Diels-Alder-reactions of silyloxyazadienes such as 510 with maleic anhydride to give 511, see Scheme 5.29. 

Trimethylsilyloxy dienes 142-147 °4 2) have been used m the ring synthesis... 

Danishefsky and coworkers have synthesized the algylcon of avermectin based on a hetero Diels-Alder reaction between trimethylsilyloxy diene (8) and chiral aldehyde (175 Scheme 49). The pyrone must come from an anti Cram-Felkin addition, so MgBr2 is used as the catalyst in this reaction. The cycloaddition reaction gives the expected product (176) and the CF diastereomer in a ratio of 3 1. The target compound (178) is obtained after a series of reactions outlined in Scheme 49. - ... 

Danishefsky and coworkers employed two hetero Diels-Alder reactions in a total synthesis of the ansa bridge of rifamycin S (Scheme 52) The first cyclocondensation reaction uses the trimethylsilyloxy diene (14) and a preincubated solution of 3-(benzoyloxy)-2-methyl-1-propanal (188) with an excess of TiCU in CHCh. The product is exclusively the syn-ACF pyrone (189). Through a Ferrier rearrangement and a sequence of oxidation-reduction steps followed by functional group manipulations aldehyde (190) is obtained. 

In the second hetero Diels-Alder reaction an anti pyrone derived from Cram-Felkin addition was needed, so trimethylsilyloxy diene (14) was allowed to react with aldehyde (190) in CH2CI2 using BF.vOEt2 as the catalyst. Under these conditions, anti-CF pyrone (191) is obtained in 57% yield, accompanied by 13% of the syn-CF pyrone. Through further manipulations compound (192), a key intermediate in the Kishi synthesis of the ansa bridge of rifamycin S, was obtained. 

In the synthesis of zincophorin, two cyclocondensation reactions are also used. In the first cyclocondensation reaction, trimethylsilyloxy diene (14) reacts with aldehyde (193) using anhydrous MgBr2 as the catalyst to give the anti-ACF pyrone (194) in 80% yield (Scheme 53). The syn.anti ratio in this reaction is 7 1. After a series of standard manipulations aldehyde (19< ) is obtained. In the second cyclocondensation reaction, anti-CF pyrone (197) results from reaction of the (4 )-r-butyidimethylsilyloxy diene (195) with aldehyde (19< ) under BF3-OEt2 catalysis (197) and its syn-CF isomers are obtained in a ratio of 4 1 and overall yield of 68%. The anti-CF aldol product is purified and cyclized to anti-CF pyrone (197) in benzene using pyridinium p-toluenesulfonate as a catalyst. Pyrone (197) converted into zincophorin (198) by a sequence of steps shown in Scheme 52. 

The power of the intramolecular Schmidt reaction is demonstrated in the concise synthesis of the Stemona alkaloid stenine. Reaction of trimethylsilyloxy diene 79 with cyclohexenone 80 and tin(IV) tetrachloride brings about a tandem Diels-Alder/Schmidt reaction to give adducts 82 and 83 in 52% and 17% yields, respectively, with the exo addition product 83 predominating. Adduct 83 contains three rings and four stereocenters present in stenine. The intramolecular Schmidt reaction is also employed as a key step in the total syntheses of 251 F (84 to 85) and (+)-aspidospermidine (87 to 88). ... 

A similar transformation results when trimethylsilyloxy-substituted allylic halides react with silver perchlorate in nitromethane. The resulting allylic cation gives cycloaddition reactions with dienes such as cyclopentadiene. The isolated products result from desilyla-tion of the initial adducts ... 

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). 

Yamamoto et al. were probably the first to report that chiral aluminum(III) catalysts are effective in the cycloaddition reactions of aldehydes [11]. The use of chiral BINOL-AlMe complexes (R)-S was found to be highly effective in the cycloaddition reaction of a variety of aldehydes with activated Danishefsky-type dienes. The reaction of benzaldehyde la with Danishefsky s diene 2a and traws-l-methoxy-2-methyl-3-(trimethylsilyloxy)-l,3-pentadiene 2b affords cis dihydropyrones, cis-3, as the major product in high yield with up to 97% ee (Scheme 4.6). The choice of the bulky triarylsilyl moiety in catalyst (J )-8b is crucial for high yield and the en-antioselectivity of the reaction in contrast with this the catalysts derived from AlMe3 and (J )-3,3 -disubstituted binaphthol (substituent = H, Me, Ph) were effective in stoichiometric amounts only and were less satisfactory with regard to reactivity and enantioselectivity. 

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. 

An outstandingly reactive diene is l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene ( Danishefsky s diene ) 4, prepared by the action of trimethylsilyl chloride on the ketone 3 in the presence of zinc chloride/triethylamine (equation 7)6. The reaction of diethyl mesoxalate with Danishefsky s diene gives the dihydropyran 5 with the (trimethylsily-loxy)dienes 6 and 7, mixtures of dihydropyrans are obtained, in which the meta-isomers predominate (equations 8 and 9)7. 

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. 

Based on bis-silylated dienes another approach to quinoxaline derivatives such as 80 (Scheme 4.10) was found [97]. Fast [4+2] cycloaddition takes place by treatment of Cgo with 2,3-bis(trimethylsilyloxy)butadiene 98, yielding the acyloin-fused fullerene derivative 100 in good yields (Scheme 4.16). The silylated diene is formed in situ by treatment of 98 at 180 °C in o-dichlorobenzene. Controlled bromination of the intermediate 99 leads to the transient diketone 101, which reacts readily in a one-pot reaction with various o-diaminoarenes to yield the quinoxaline-fused fullerenes 102. 

The reaction of carbohydrate-derived imines with the Danishefsky diene, ( )-1 -methoxy-3-(trimethylsilyloxy)butadiene, to form heterocycles via the open-chain adducts (for assignment, see pp 456 and 478)130. 

Some attention has been paid in our group to 1,3-diazadienes while working with trimethylsilyl imines, since these reagents allowed us to readily prepare a variety of 2-trimethylsilyloxy- and 2-trimethylsilylthio-1,3-dienes 357 (89S228) (Scheme 79). We first tested their potential as heterodienes toward aromatic isocyanates and found that treatment of a dichloromethane solution of 357 and isocyanate at room temperature resulted in a clean conversion into triazinedione and 4-thioxotriazinone derivatives 358 in 84-96% yield. 

Fluorinated dienes have been described, though again, the incidence is rare. Treatment of an a,/ -unsaturated-a-fluoroaldehyde with chlorotrimethyl silane afforded [369] the l-trimethylsilyloxy-2-fluorobutadiene which underwent [4 + 2] cycloadditions with dienophiles, though more slowly than its non-fluori-nated counterpart, and with lower regioselectivity (Eq. 148). 

---