Danishefsky trimethylsilyloxy dienes

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]. 

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 with 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky s dienes) exhibit abnormal exo-selectivity. Electrostatic repulsion between the nitro and the silyloxy group of the diene induces this abnormal exo-selectivity (Eq. 8.10).17 This selective reaction has been used for the asymmetric synthesis of various natural products as shown in Scheme 8.6. 

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]. 

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. 

Danishefsky s diene l-methoxy-3-trimethylsilyloxy-l,3-butadiene DBN 1,5-diazobicyclo [4.3.0]non-5-ene... 

The reaction of N-(terf-butoxycarbonyl)leucinal 2-41 a by Danishefsky et al. with l-methoxy-3-trimethylsilyloxy-l,3-butadiene 2-10 gave the pyrones 2-42 and 2-43 with an induced diastereoselectivity of 9 1 in favour of the syn-com-pound in the presence of Eu(hfc)3 [96]. Later Garner [97] used a N-Boc-serine derived aldehyde 2-41 b and Danishefsky s diene 2-10. In both cases a chelation-control forming a complex between the nitrogen and the oxygen could explain the obtained selectivity. In the presence of HMPA chelation is minimized to give a higher extent of the anfi-product 2-43 (Fig. 2-12) [97]. 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

Further extension of the reaction pool of Schilf bases 138 was achieved by their reaction with tran -l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene) to give 2-substituted 5,6-didehydro-piperidin-4-ones 164 [135,136] (Scheme 10.54). The reaction is considered to be a sequence of an initial Mannich reaction between the imine and the silyl enol ether, followed by an intramolecular Michael addition and subsequent elimination of methanol. If the reaction was terminated by dilute ammonium chloride solution, then the Mannich bases 163 could be isolated and further transformed to the dehydropiperidinones 164 by treatment with dilute hydrochloric acid. This result proved that the reaction pathway is not a concerted hetero Diels-Alder type process between the electron-rich diene and the activated imine. The use of hydrogen chloride as a terminating agent resulted in exclusive isolation of the piperidine derivatives 164 formed with... 

Among the more reactive and synthetically useful dienes are doubly and triply activated alkoxy- and amino-substituted dienes, such as ( )-l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene),( )-l-(dimethylamino)-3-(fert-butyldimethylsilyloxy)-1,3-butadiene (Rawal s diene)-, and 1,3-dimethoxy-l-(trimethylsilyloxy)-1,3-butadiene (Brassard s diene). As illustrated below, the cyclo-addition products arising from these dienes can either be hydrolyzed or treated with fluoride ion to remove the silyl group, which is followed by (3-elimination to provide conjugated cyclohexenones. 

Dienes substituted with RO and R2N groups (e.g., Danishefsky s diene, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene) are particularly good substrates for Diels-Alder reactions, but alkyl-substituted dienes and even butadiene itself are common substrates. Benzene rings are very poor dienes in Diels-Alder reactions,... 

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. 

Enantiomerically pure ruthenium complexes [CpRuLL (CH2=Cll2)]PF6 17, where LL is (S,S)-Chiraphos or (-)-Diop, catalyze the cyclocondensation of benzaldehyde (2 a) with ( )-l-methoxy-3-trimethylsilyloxy-l,3-butadiene (16. Danishefsky s diene), albeit with low optical yields of 25% and 16% ee (18 as a major isomer), respectively39. 

The application of Lewis acids, such as the europium salt Eu(fod)3, in [4+2] cycloadditions of carbonyl compounds (e.g. glyoxylates and aldehydes) with 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene) has been intensively examined by Danishefsky et al. and employed in natural product synthesis. ... 

Danishefsky and coworkers have used the racemic P-phenylsulfinyl-a,P-unsaturated ketone (160) as an a,P-ethynyl carbonyl synthetic equivalent and found that the phenylsulflnyl group did not compete with the carbonyl group in determining the regioselectivity of cycloaddition with the l-methoxy-3-trimethylsilyloxy-1,3-butadiene (161), now known as Danishefsky s diene [140] (Scheme 5.54). Loss of methanol and phenyl sulfenic acid from the initial cycloadduct (162) gave the aromatic product (163). 

We assumed that electron-rich dienes should allow for aza-Diels-Alde reactions with the imines 2 5 at lower temperature and with highei stereoselection. Therefore, the aldimine 2 9 generated from the galactosylamine 24 and pyridine-3-aldehyde, was treated with l-methoxy-3-trimethylsilyloxy-butadiene (Danishefsky s diene ). Two equivalents of zinc chloride in tetrahydrofuran must be applied for the reaction to proceed. The first obviously is coordinated to the pyridine nitrogen and, thus, completely inactivated. The second initiates the cyclocondensation to give the N-galactosyl-dehydro-piperidinone derivative 30 in high yield and with a diastereoselectivity of more than 20 1 (eq. 14) 1. 

In 1995, Katsuki and Yamashita [11a] found that Mg-salen complex and Co- or Cr-salen complexes served as Lewis acid catalysts for asymmetric Diels-Alder reactions and hetero Diels-Alder (HDA) reaction of Danishefsky s diene (l-methoxy-3-trimethylsilyloxy-l,3-butadiene) with aldehydes. Later on, they found that second-generation (R,S)-(ON )Ru-salen complex bearing chiral binaphthyl and ethylenediamine units also served as a catalyst for asymmetric HDA reaction between Danishefsky s diene and benzaldehyde [llbj. Recently, in 2001 they reported that (R,S)-Ru(II)-salen complex served as a good catalyst for... 

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