Silyl enol ethers, reactions with dienes

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>. 

Cyclopropanation of l,3-dienes. a,0-Unsaturated carbenes can undergo [4 + 2]cycloaddition with 1,3-dienes (12, 134), but they can also transfer the carbene ligand to an isolated double bond to form cyclopropanes. Exclusive cyclopropanation of a 1,3-diene is observed in the reaction of the a,(3-unsaturated chromium carbene 1 with the diene 2, which results in a frans-divinylcyclopropane (3) and a seven-membered silyl enol ether (4), which can be formed from 3 by a Cope rearrangement. However, the tungsten carbene corresponding to 1 undergoes exclusive [4 + 2]cycIoaddition with the diene 2. 

A similar enantiomer-selective activation has been observed for aldol " and hetero-Diels-Alder reactions.Asymmetric activation of (R)-9 by (/f)-BINOL is also effective in giving higher enantioselectivity (97% ee) than those by the parent (R)-9 (91% ee) in the aldol reaction of silyl enol ethers (Scheme 8.12a). Asymmetric activation of R)-9 by (/f)-BINOL is the key to provide higher enantioselectivity (84% ee) than those obtained by (R)-9 (5% ee) in the hetero-Diels-Alder reaction with Danishefsky s diene (Scheme 8.12b). Activation with (/ )-6-Br-BINOL gives lower yield (25%) and enantioselectivity (43% ee) than the one using (/f)-BINOL (50%, 84% ee). One can see that not only steric but also electronic factors are important in a chiral activator. 

The first reference to 2-trimethylsilyloxy-l,3-butadiene (1) was a report2 of its reaction with tetracyanoethylene by Cazeau and Frainnet without mention of any experimental details. Later, Conia3 reported its synthesis in 50% yield with only a reference made to the usual House procedure4 for silyl enol ethers. The diene 1 has also been prepared using lithium diisopropylamide as base and chlorotrimethylsilane in tetrahydrofuran-ether (1 1) in yields up to 65%, but on a smaller scale.s... 

A short access to retinal was reported by Duhamel et al. [54,55] via the enolate of prenal, prepared from the corresponding silyl enol ether or enol acetate. The diene reacted with P-ionylideneacetaldehyde to give the dihydropyranol as the single reaction product. The dihydropyranol was... 

In another attempt, we reached the tetracyclic structure 42 via two consecutive [4 + 2] cycloaddition reactions. Reaction of 3-cyano-4-benzopyrone 31 with Danishefsky s diene 38 in toluene at 300 °C for 96 h provided the desired cycloadduct 39 in 80% yield with an endo exo ratio of 1 2 [Scheme 8]. Hydrolysis of the silyl enol ether in 39 using TMSBr in CH3CN at room temperature proved to be feasible but slow, and afforded the enone 40 in 90% yield. Reaction of diene 41 with enone 40 in the presence of 2.5 equiv of BF3-Et20 yielded tetracycle 42 in 25% yield with an endo exo ratio of 1 1 after 120 h at room temperature.49... 

A very useful intermediate for the attachment of further functionalities to Cgo is obtained by reaction of the fullerene with 2-[(trimethylsilyl)oxy]buta-1,3-diene, followed by hydrolysis of the resulting silyl enol ether under formation of a fullerene-fused cyclohexanone (214) which is reduced to the racemic alcohol ( )-215 (Scheme 1.18).374 Because of their great synthetic potential, silyloxy-substituted dienes, such as Danishefsky diene type systems,375-377 have been widely used in the preparation of fullerene derivatives, mostly in the form of stereoisomeric mixtures.378-383... 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

In the presence of 10 mol % Sc(OTf)3, A-benzylideneaniline reacts with 2-trans-l-methoxy-3-trimethylsiloxy-l, 3-butadiene (Danishefsky s diene) [23] to afford the corresponding aza Diels-Alder adduct, a tetrahydropyridine derivative, quantitatively (Eq. 7) [24]. In the reaction of A -benzylideneaniline with cyclopentadiene under the same conditions, on the other hand, the reaction course ehanged and a tetrahydroqui-noline derivative was obtained (Eq. 8). In this reaction, the imine aeted as an azadiene toward one of the double bonds of cyclopentadiene as a dienophile [25]. In the reaction with 2,3-dimethylbutadiene a mixture of tetrahydropyridine and tetrahydroqui-noline derivatives was obtained. A vinyl sulfide, a vinyl ether, and a silyl enol ether worked well as dienophiles to afford the tetrahydroquinoline derivatives in high yields [26,27]. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Compounds with an additional 2-vinyl group, easily available in two steps from a,J -unsaturated ketones, are of special interest. If the reactive vinyl ketone moiety is liberated, it can be trapped in situ by suitable nucleophiles, e.g. CH-acids, generating polyfunctional compounds or by a diene unit which undergoes an intramolecular Diels-Alder reaction (equation 93). Besides, radical additions to the vinylcyclopropane are also possible giving silyl enol ethers as ring-opened products . Future synthetic applications of theses processes are obvious. 

Two homo Diels-Alder reactions and a hetero Diels-Alder reaction, each using a silyloxydiene, have been used in a total synthesis of vinemycinone methyl ester (236) by Danishefsky (84JA2453 85JA1285). Ketoaldehyde 231, prepared by two Diels-Alder cycloadditions, reacted with diene 230 in chloroform in the presence of Eu (fod)j to produce the silyl enol ether... 

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... 

The most obvious methods of activating the y-position would involve enamines19 and silyl enol ethers.20 These are the more stable of the various specific enol equivalents (chapter 10) and thus are more suited to thermodynamic control. Extended enamines 55 are easy to make and are excellent electron-rich dienes for the Diels-Alder reaction but react in the a-position with most alkylating agents. 

This unsaturated acid was made by a Diels-Alder reaction, but not the one you might have expected. Danishefsky invented a special diene Danishefsky s diene 159 for the introduction of enone functionality in the Diels-Alder reaction and here you see an application. The Diels-Alder adduct 161 is a silyl enol ether with a leaving group in the (1-position and it hydrolyses easily to the enone 162. 

---