Dienes siloxydienes

Coupling of alkenylcarbene complexes and siloxy-substituted 1,3-dienes affords vinylcyclopentene derivatives through a formal [3C+2S] cycloaddition process. This unusual reaction is explained by an initial [4C+2S] cycloaddition of the electron-poor chromadiene system as the 471 component and the terminal double bond of the siloxydiene as the dienophile. The chromacyclohexene intermediate evolves by a reductive elimination of the metal fragment to generate the [3C+2S] cyclopentene derivatives [73] (Scheme 26). 

Tetrahydro-2-pyridones are also produced by a [4+2] cycloaddition of l-aza-2-siloxydiene with simple dienes in a Lewis acid-catalyzed reaction (Equation 142) <2004S2222>. In an analogous manner, hydrazone derivatives have been in aza-[4+2] cycloadditions with reactive dienophiles which can be trapped with aldehydes to form highly functionalized piperidines (Scheme 88) <2004AGE2001, 2004JOC8429>. 

Danishefsky and co-workers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is used as an NMR shift reagent, promoted hetero Diels-Alder reactions [30] of aldehydes with siloxydienes and induced enantiomeric enrichment (Sch. 1) [31]. Suitable substituents on the dienes were introduced to improve the extent of asymmetric induction. The best result was obtained in the reaction of benzaldehyde with l-methoxy-2-methyl-3-(trimethyl-siloxy)- , 3-butadiene using 1 mol % Eu(hfc)3 the enantiomerie excess was, however, moderate (58%). The authors maintained that the major advantage of lanthanide catalysis lay in the survival of otherwise labile systems used as adducts. 

Trace amounts of complexes 3 and 20 promote the synthesis of optically pure, multiply functionalized, versatile intermediates such as pyrones or lactones from activated, acid-labile siloxydienes with aldehydes. The reagents typically work under mild conditions and therefore promote the survival of valuable functionality in the dienophile, the diene, and cycloadduct [105-107]. As a consequence this procedure is applied in the total synthesis of various natural products, often requiring an intramolecular Diels-Alder approach [106]. Specific interactivity of the chiral precatalyst Eu(hfc)3 (hfc = 3-(heptafluorpropylhydroxymethylene)-D-camphorate with Danishefsky s diene bearing a chiral auxiliary resulted in cycloaddition products of high diastereofacial excess (95 % eq. (8)) [105]. 

In the last decade a variety of catalytic asymmetric DA reactions wifh alkenes has been developed most, however, involve the use of a cychc diene, particularly cyclopentadiene. There are a few examples of catalytic asymmetric reactions of siloxydienes with alkenes. Corey et al. have reported enantioselective cycloaddition of sil-oxydiene 106 to mefhacrolein as the key step of fhe asymmetric synfhesis of cassiol (Scheme 10.116) [314]. Recently, Rawal et al. have demonstrated that Cr(III)-salen complex 108a catalyzes the cycloaddition of l-amino-3-siloxy-l,3-dienes to a, -unsa-turated aldehydes wifh high enantioselectivity [315]. The highly functionalized cyclohexene products have been used for alkaloid synthesis. Ghosez et al. have introduced asymmetric DA reaction of siloxy-substituted azadienes 109 under catalysis by Cu(II)-box complex 70a [316]. 

Since Danishefsky demonstrated that activated dienes, such as siloxydiene (commonly referred to as Danishefsky s diene) react with a wide spectrum of aldehydes to afford 5,6-dihydro-y-pyrones in 1982 [l],the hetero-Diels-Alder reaction has attracted a great deal of attention over the last two decades [2,3]. The use of asymmetric catalysis in these reactions is overwhelmingly associated with heterodienophiles. Especially, the cyclocondensations of activated dienes with aldehydes or their derivatives are of particular importance, providing a multitude of opportunities for the highly efficient regio- and stereoselective construe-... 

In the dienol silyl ether (63), where the 7-selectivity of the siloxy diene is enhanced by the second sil-oxy substituent, reactions with electrophiles occur exclusively in the 7-position as illustrated in Scheme 43.68 132 The same 7-selectivity is observed for the siloxydiene (58) derived from a 1,3-diketone.64... 

Carboxyl-substituted N-sulfonylimines have also been used in [4 + 2] cycloadditions, and some examples are shown in Scheme 2-11. - Imine 14 adds regioselectively to isoprene to give only one adduct, but diene 15 surprisingly afforder a 3 1 mixture of adducts. The major exo adduct produced from siloxydiene 16 was recently used in total synthesis of the piperidine alkaloids isoprosopinine B and deoxyprosopinine. The highly oxygenated diene 17 was found to react with both acyclic N-sulfonylimine 18 and cyclic imine 19 to afford cycloadducts. 

All these investigations also showed a distinct difference from reactions with the highly successful siloxydienes related to the Danishefsky diene. [25, 26] The hydrolysis of the final cycloadducts (enolethers or enami-nes) affords the preparatively valuable ketones in both cases (vide infra) but the trivalent aminosubstituent allows the attachment of chiral axiliaries at C-2 much more easily... 

Diels-Alder reaction. 1,3-Dialkoxy-l,3-butadienes are not readily available however, they are potentially useful dienes for (4 + 2] cycloadditions. The siloxydiene, on the other hand, is readily available and has been shown to be useful for organic syntheses. For example, (1) reacts with maleic anhydride at room temperature to give the adduct (2) work-up with HCl in THF gives the methoxyketo anhydride (3)in 93% yield ... 

De Meijere and co-workers have reported on the reactions of the parent vinyldiazomethane and chlorinated vinyldiazomethanes with oxygenated dienes. Rhodium(II) acetate catalyzed decomposition of these vinyldiazomethanes in the presence of 2-siloxydienes proceeds in good overall yields (Scheme 15). Because the vinylcarbenoid does not contain the donor/acceptor combination of the carbenoids derived from vinyldiazoacetates, the stereoselectivity of the cyclopropanation is poor and mixtures of the [344] annulation products and the trans-divinylcyclopropanes are formed. 

Danishefsky reported some years ago that acyclic, unactlvated imines undergo Lewis acid catalysed cycloaddition with siloxydienes to give six-membered nitrogen heterocycles. Two reports have now extended these observations to include the reaction of cyclic imines with dienes. Danishefsky s group has also described the cycloaddition of dihydro-B-carbolines with three siloxydienes to... 

Several groups exploited the power of the intermolecular Diels-Alder reaction early in their syntheses for the formation of substituted cyclohexenes. In his synthesis of platencin, Nicolaou used a Danishefsky-like diene in an asymmetric Diels-Alder reaction for the synthesis of a chiral cylohexenone. Kanai and Shibasaki developed a catalytic asymmetric Diels-Alder reaction promoted by barium isopropoxide for the first step in their synthesis of Tamiflu. Danishefsky constructed the cyclohexene ring in paecilomycine A by employing a highly e t/o-selective Diels-Alder reaction of siloxydiene 115 and enyne dienophile 116 to yield target 117. ... 

In the Diels-Alder reaction of siloxydiene with benzaldehyde in the presence of an organoaluminum compound having an optical active bulky binaphthol as shown in eq. (7.30), the reaction proceeds via the intermediate burst of aluminum coordinated with carbonyl oxygen of benzaldehyde. As the aluminum is bonded with two naphthalene bond with bulky Si(3,5-xylyl)3, the highly stereospecific product is obtained by the restriction of the reaction direction of dienes [44,45,49,49a]. 

Shibasaki et al. also developed a chiral baiium-catalyzed asymmetric Diels—Alder reaction of a siloxydiene with fumarate for the synthesis of an optically active Tamiflu precursor [104] for a review of asymmetric Diels—Alder reactions, see [105]. Metal exchange from silicon to barium occurred via activatitm by CsF to form an activated chiral diene, which reacted with fumarate with high enantioselectivity (Scheme 11). 

As usual there has been considerable activity in the field of siloxydiene cycliza-tion reactions, but probably the most significant developments in this area over the past twelve months have been in the use of such dienes to synthesize 2,3-dihydro-Y-pyrones (Scheme 16). 

Although phosphoric acid has been employed for the activation of carbon-nitrogen double bond, Yamamoto et at. designed a stronger chiral Bronsted acid in order to expand the scope of the chiral Bronsted acid catalyzed reactions. A N-triflyl phosphoramide (50), bearing BINOL backbone, catalyzed the Diels-Alder reaction of a,p-unsaturated ketone with electron-rich diene ((2, )-siloxydiene is major) to give cyclohexene derivatives in high ees (Scheme 2.106) [184]. 

The enantioselective hetero-Diels-Alder reaction of siloxydienes, such as Danishefsky s and Brassard s dienes, with imines provides an efficient route for the preparation of functionalized nitrogen-containing heterocycles in optically active forms. Akiyama and coworkers reported the first catalytic enantioselective hetero-Diels-Alder reaction of Danishefsky s diene (21) with aromatic imines 20 using chiral phosphoric acid catalyst la (Scheme 11.7a) [14]. The desired dihydropyridi-nones 22 were obtained in good yields with high enantioselectivities. Notably, the addition of an equimolar amount of acetic acid was effective in improving the enantioselectivity. Akiyama and coworkers also reported an enantioselective... 

Wender et al. reported an interesting example that appears to exhibit a cooperative or matched-matched case for the chiral Lewis acid-catalyzed HDA of an aldehyde bearing a chiral auxiliary and Danishefsky s diene (Scheme 65) [119]. Subjecting chiral aldehyde 245 and siloxydiene 231 to Jacobsen s catalyst resulted in the formation of 2,3-DHP 246 in 88 % yield with excellent diastereoselectivity (dr = 33 1). 

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