1.3- dienes siloxy-substituted

Reaction with Electron-Rich Siloxy-Substituted 1,3-Dienes. 79... 

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). 

Diels-Alder Reactions of Siloxy-substituted 1,3-Diene... 

In the nineteen-eighties stoichiometric amounts of conventional Lewis acids such as TiCl4, AICI3, SnCU, BFs-Olt,., Mgl r, and ZnCU were frequently used for HDA reactions of siloxy-substituted dienes with heterodienophiles [286, 287]. Danishefsky et al., however, found that a lanthanide shift reagent such as Eu(fod)3 can promote the cycloaddition catalytically [294]. Several Bronsted and Lewis acids have recently been shown to have high catalytic activity in the DA reaction of siloxy-substituted dienes in non-aqueous or aqueous media, and elaboration of Lewis acids has achieved unique chemo- and regioselectivity. 

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]. 

In most of the successful Diels-Alder reactions reported, dienes containing no heteroatom have been employed, and enantioselective Diels-Alder reactions of multiply heteroatom-substituted dienes, e.g. Danishefsky s diene, are rare, despite their tremendous potential usefulness in complex molecular synthesis. Rawal and coworkers have reported that the Cr(III)-salen complex 15 is a suitable catalyst for the reaction of a-substituted a,/ -unsubstituted aldehydes with l-amino-3-siloxy dienes [21] (Scheme 1.28, Table 1.12). The counter-ion of the catalyst is important and good results are obtained in the reaction using the catalyst paired with the SbFg anion. 

The present homoallylation with siloxy- and methoxy-substituted dienes may be of great synthetic use. The product 42 is easily converted to anti-5-phenyl-5-hydroxy-3-methylpentanal (Scheme 9) hence the diene 41f may be regarded as a synthetic equivalent of a bis-homoenolate of 3-methylbutanal, being capable of introducing 1,3-anti relationship between the methyl and hydroxy groups in the product. 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Little quantities of iodotrimethylsilane catalyse the rearrangement of 2-siloxy cyclopropanes to their isomeric silyl enol ethers (equation 102), whereas an equimolar amount of this silylating agent gives a highly donor substituted diene. Both product types are promising intermediates, yet their chemistry still remains to be explored. 

Nucleophiles other than hydrides can be used, such as aUylsilanes, siloxy-dienes, or silyl enol ethers, to access substituted THPs from cyclic ketals. Rych-novsky et al. and Wipf et al. synthesized one THP of leucascandrolide A from ketal 76 by using a nucleophilic addition of aUylsilane in the presence of BF3 Et20. The diastereoselectivity of the reaction was explained by an axial attack on the half-chair oxocarbenium intermediate. The double bond was then transformed into the corresponding aldehyde by ozonolysis to afibrd further functionalizations (Scheme 38) (2001JA8420 2002CC2066). 

Domino metathesis of siloxy-tethered dienynes offers attractive opportunities for the synthesis of stereochemically defined 1,3-dienes after desilylation [21]. These reactions also allow the efficient preparation of highly substituted cycloolefins, which is illustrated in Scheme 2.43 [21b,c]. Selective double cydization of silaketal 118 via initiation at the monosubstituted alkene led to a fused 6/7-bicychc product which was subsequently desilylated to afford the triol 119 in high overall yield. 

Synthesis of Vinylogous Esters.—The versatility of 3-ethoxycyclohex-2-enone as a starting material for the synthesis of substituted cyclohexanones has again been demonstrated. A range of vinylogous esters are obtained by the Lewis-acid-catalysed cyclocondensation of siloxy-dienes with saturated and ap-unsaturated aldehydes (Scheme 80). The reactions are applied to the synthesis of several compounds of biological interest. 

Another cycloaddition, in which this time the silyl enol ether functions as a dienophile, is the SnCl4-catalysed addition of butadiene to (180 R = Me) giving (181). If R = H in the starting material a 4 + 3 reaction takes place, producing the seven-membered ring (182). Flash-vacuum thermolysis of P-keto-trimethylsilyl enol ethers has been used in a substituted furan synthesis, and the same process has been used to prepare a-allenic acids (183) from siloxy-dienes. ... 

Siloxyindenes add to heterodienophiles to give azaC103annulenes, 3-siloxy buta-1,3-dien-1-yl substituted glucopyranosides add to benzoquinones as does l-MeO-l-fie siO butadienes to naphthaquinone to give anthraquinones.All trans 1-siloxy cunjugated trienes add dienophiles across C(3)-C(6) while the... 

Aungst and Funk reported studies on the related a-siloxy- 3-substituted acroleins such as 84 almost contemporaneously (Scheme 18.17) [23]. Siloxyacrolein 84 was prepared by a retro-hetero-Diels-Alder reaction of dioxin derivative 83. Compared with 79, compound 84 bears an additional carbon substituent that would further stabilize siloxyallyl cation 85 and favored its formation, with the result that even acyclic dienes like butadiene underwent [4+3] cycloaddition effectively. 

---