Siloxydiene

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). 

Karachine (505) (253), the first natural protoberberine incorporating an acetone unit, was synthesized from berberine (15) (254). Heating of 15 with siloxydiene 503 in dimethyl sulfoxide afforded karachine (505) in 66% yield through Mannich condensation, intramolecular Michael addition, and then further Mannich condensation via 504 (Scheme 106). 

The key chiral intermediate 4, highly functionalized hydroisoquinoline, was obtained by a Diels-Alder reaction between siloxydiene 5 and chiral dienophile 6 which was prepared from Z-serine [4]. Ruche reduction of enone 4 gave allyl alco-... 

Past methods used to synthesize 7-pyrones consist of the acylation of methoxy-butyne9 or 4-methoxy-3-buten-2-one10 followed by acid-catalyzed hydrolysis and cyclization. Addition of ketenes to siloxydienes followed by acid-catalyzed elimination has also been employed.11 The present method is superior to these procedures because of the greater diversity of substituted 7-pyrones that can be constructed, and because of the fact that the previous methods demand the use of strong base and low temperatures that make them less suited for scale up. 

The three-phase test has been used to distinguish between associative and dissociative mechanisms. Thus, in this case the negative results in the trapping of the intermediate with dienic polymers seem to support a stepwise mechanism in the formation of cyclocondensation adducts with siloxydienes and l-azetin-4-one. 

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>. 

Table 6.37 Taddol-catalyzed HDA reactions of 1-amino-3-siloxydienes.

Taddol-Catalyzed Diels-Alder Reactions of l-Amino-3-Siloxydienes [88] (p. 242)... 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

Zinc(II) chloride is also the best Lewis acid for the cycloaddition of hemiacetal 3. a di-fluoroacetaldehyde equivalent, with siloxydienes. Only one regioisomer 4 is obtained, in agreement with the prediction from orbital coelTicients. ... 

Siloxydiene 341 was specifically designed for the preparation of 1,3-methoxy-hydroxy substituted aromatic fragments. The initially formed adducts, for example 342, are prone to easy hydrolysis and elimination of methanol to lead eventually to aromatic derivatives such as 343, used further as a key intermediate in the synthesis of the plant growth inhibitor lasiodiplodine. " ... 

Aldehydes and siloxydienes undergo cyclocondensation with Bp3-Et20 to form pyranones (Eq. 58) [104]. The stereoselectivity is influenced by the solvent. 

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]. 

Kerwin, J. F., Jr., Danishefsky, S. On the Lewis acid catalyzed cyclocondensation of imines with a siloxydiene. Tetrahedron Lett. 1982, 23, 3739-3742. 

Bednarski, M., Maring, C., Danishefsky, S. Chiral induction in the cyclocondensation of aldehydes with siloxydienes. Tetrahedron Lett. 1983,24,3451-3454. 

Oxazolidinone-substituted siloxydiene 105b also is applicable in DA reactions with electron-deficient alkenes under slightly vigorous conditions (Scheme 10.108)... 

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]. 

Hetero-Diels Alder Reaction of Aldimines with Siloxydienes... 

The enantioselective hetero Diels Alder (D A) reaction of siloxydienes, such as... 

Scheme 3.24 Enantioenriched nitrogen heterocycles by hetero D A reaction of siloxydienes.

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-... 

Casiraghi, G., Rassu, G., Spanu, P and Pinna, L., J. Org. Chem., 1992, 57, 3760 idem, Tetrahedron Lett, 1994, 35, 2423 Furan-, pyrrole-, and thiophene-based siloxydienes for synthesis of densely functionalised homochiral compounds , Casiraghi, G. and Rassu, G., Synthesis, 1995, 607. 

Similar y-regioselectivity has been observed in the reaction of the steroidal siloxydiene (115) with the Eschenmoser s salt (116) to give the Mannich adduct (117). 

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