Siloxy diene syntheses with

Asym. diene synthesis with l-alkoxy-3-siloxy-1,3-dienes... 

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 HDA reaction allows for rapid access to chiral six-membered heterocyclic structures that serve as valuable intermediates in organic synthesis. The first highly enantioselective HDA reaction promoted by a chiral hydrogen bond donor was reported from the Rawal laboratory. While investigating the cycloaddition reactions of amino-siloxy diene 115, it was observed that this diene was exceptionally reactive to heterodienophiles, and underwent HDA reactions with various aldehydes at room temperature, even in the absence of any added catalyst (Scheme 6.14). Subsequent treatment of the intermediate cycloadducts (116) with acetyl chloride afforded the corresponding dihydro-4-pyrones (117) in good overall yields [101]. Further studies of this reaction revealed a pronounced solvent effect,... 

Recently, a few examples of imino Diels-Alder reactions using azetinones as dienophiles have been described in work aimed at synthesis of carbapenems. In one sequence of reactions, acetate (34) was treated with a Lewis acid in the presence of a siloxy diene to afford adduct (36) (equation ll). This transformation presumably involves imine (35) which reacts both regio- and stereo-selectively with the diene. Adduct (36) was converted in a few steps to carbapenem (37). 

The three-step procedure above illustrates the usefulness of a 1-amino-3-siloxy diene for the synthesis of functionalized cyclohexenones and is representative of the general usefulness of the dienes. The first step in the sequence, the Diels-Alder reaction between the parent aminosiloxy diene nd methyl acrylate, cleanly produces the cycloadduct as a mixture of endo and exo diastereomers. This diene also reacts with many other dienophiles and the results are summarized in Table I.3 The cycloadducts are generally obtained as mixtures of endo-exo diastereomers, except for the reactions with N-phenylmaleimide and methacrolein, which proceed with high endo selectivity, and with dimethyl maleate, which gives predominantly the exo adduct. 

Siloxy dienes have been shown to be highly effective in both the Diels-Alder reaction and the hetero Diels-Alder (diene-aldehyde cyclocondensation) reactions. Diene 3 has been used in the synthesis of several important naturai products including zincophorin, rifamycin, and the Prelog-Djerassi laclone. Recently, under the aegis of chiral catalysts, 3 has been shown to participate in the diene-akJehyde cyclocondensation reaction with several aldehydes to afford cycloadducts of very high enantiomeric excess. ... 

Danishefsky et al. have achieved a synthesis of a methyl peracetyl-oc-hikosaminide (216), an undecose degradation product of the anthelmintic hikizimycin, in which use is twice made of the siloxy-diene aldehyde Diels-Alder reaction. Thus, the reaction between the diene (211) and furfural with [EuCfod) ] catalysis leads to the pyrone (212) which, after elaboration to (213), is again condensed with (211), but this time with magnesium bromide catalysis, which causes addition of the remaining four carbon atoms of the undecose in a chelation-controlled and, notably, a topically exo reaction. Elaboration of (215) to the required protected hikosamine (216) then follows in a straightforward manner. 

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 intriguing application reported by Scettri was the trans- and enantiose-lective synthesis of 2,3-disubstituted 2,3-dihydropyran-4-ones through the 2-catalyzed aldol reaction of the siloxy diene with aldehydes followed by acidic treatment for the subsequent ring closure (Scheme 7.7) [9]. 

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>. 

Stereospeeific synthesis of IJ-dieues. Corey el al. have described a new synthesis of 1,3-dienes based on the highly stereospeeific cis addition of alkylcopper reagents to a,p-acctylenic carbonyl compounds (3, 108). Thus the reaction of methyl 4-trimethyl-siloxy-2-nonynoate (I ) in THF with divinylcopperlithium (1.25 cq.) at - 90° and then at — 78° affords the pure madduct (2) in > 90% yield. Treatment of (2) with melhanolic hydrochloric acid effects cleavage of the trimethylsilyl ether and lactonization to give (3). 

BICYCLOPROPYLIDENE possesses unique reactivity toward a wide range of electrophiles and nucleophilic carbenes. (E)-I-DIMETH YLAMINO-3-tert-BUTYLDIMETHYL-SILOXY-1,3-BUTADIENE is a highly reactive diene for Diels-Alder reactions, as described in an accompanying procedure for the synthesis of 4-HYDROXYMETHYL-2-CYCLOHEXEN-1-ONE via the Diels-Alder reaction with methyl acrylate. Finally, this section concludes with the preparation of DIETHYL [(PHENYLSULFONYL)METHYL]PHOSPHONATE, a reagent that is very useful for synthesis of [Pg.285]

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]. 

Danishefsky used a variety of silyloxybutadienes in Diels-Alder reactionsin place of alkoxy and acetoxy derivatives. Treatment of these cycloadduct siloxy derivatives with fluoride (sec. 7.3.A.i) will unmask an enol moiety, which tautomerizes to the carbonyl under very mild conditions. Silyloxy dienes have become very popular for this type of reaction. In Weinreb s synthesis of phyllanthine,150 imine 144 reacted with diene I43151 in the presence of Yb(OTf)3 to give 145. Hydrolysis converted this functionality to the conjugated ketone 146 in 84% overall yield. The previous development of 143 as a reagent was due to several unsuccess-... 

An alternative method for incorporating a sulfone moiety into a carbon framework for the RBR involved an elegant four-component coupling between sulfur dioxide, silyl enol ethers 19 and 20, and iodide 21 (Scheme 8.71. The mechanism presumably comprises addition of 1-siloxy-1,3-diene 19 to sulfur dioxide, reaction of the resulting aldehyde with silyl enol ether 20, and then attack of the resulting sulfinate on the a ky iodide 21. The product 22, obtained as four diastereomers, was converted by the RBR to an intermediate that comprised a formal total synthesis of apoptolidin (see Section R.fiT... 

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