1 - Methoxy-3-trimethylsiloxy-1,3-butadiene

METHOXYPHENYL)-1,2,5,6-TETRAHYDROPYRIDINE, 68, 188 N-(4-Methoxyphenyl)-Z-4-(trimethylsilyl)-3-butenamine, 68,188 a-Methoxy-o-trifluoromethylphenylacetyl chloride, (S)-(+)-, 69, 15 1-Methoxy-3-(trimethylsiloxy)-1,3-butadiene Silane, [(3-methoxy-1-methylene-... 

C. 5 -Methoxycyclohexan- -one- > A -dicarboxylic acid anhydride. To 3.00 g (0.174 mol) of 1-methoxy-3-trimethylsiloxy- 1,3-butadiene at 0°C (ice bath) is added a total of 980 mg (0.01 mol) of freshly sublimed maleic anhydride in portions of 70-80 mg each over a period of 25 min. When the addition is complete, the ice bath is removed and the clear solution is stirred for 15 min at room temperature (Note 7). Three 5-mL portions of a solution of tetrahydrofuran (35 mL) and 0.1 N hydrochloric acid (15 mL) are added and the solution is stirred for 1 min. The remaining acid solution (35 mL) is added all at once and the resulting solution is poured into 100 mL of chloroform and treated with 25 mL of water. The organic layer is separated and the aqueous layer is extracted four times with 100-mL portions of chloroform. The extracts are combined and dried over anhydrous magnesium sulfate. The solvent is then removed under reduced pressure (Note 8) to provide 2.0 g of an oil which solidifies. Pentane (10 mL) is added to the oily solid and small portions... 

The procedure described here is a scale-up of the published method2 for the preparation of 1 -methoxy-3-trimethylsiloxy-1,3-butadiene (2) from readily available reagents. The preparation of this diene has recently been complemented by a report of the preparation of l,3-bis(trimethysiloxy)-l, 3-butadiene,3 and earlier by a reported synthesis of a 1,3-dialkoxy-l, 3-butadiene.4... 

The second step in the above sequence, deprotonation followed by silylation of the resulting enolate, was not successful under standard lithium diisopropylamide (LDA) conditions, presumably because silylation of the lithium enolate was slow. The deprotonation/silylation can be carried out effectively using KHMDS, which is available from Aldrich Chemical Company, Inc., as a 0.5 M solution in toluene. This protocol is quite general for the preparation of various dienes containing different silyl and amino groups as illustrated in Table I.5-7 For preparative scale reactions, such as that described above, the use of NaHMDS was preferred as it is available from Aldrich Chemical Company, Inc., as 1.0 M solution in THF. The procedure described here also provides a convenient and high-yielding preparation of Danishefsky s diene (1-methoxy-3-trimethylsiloxy-1,3-butadiene).8... 

Interestingly, the reactions of (i )-2,3-0-isopropyUdene-D-glyceraldehyde (35) with l-methoxy-2,4-dimethyl-3-(trimethylsiloxy)butadiene, catalyzed by (-f)-34 and (-)-34, respectively, involved a high degree of double stereodifferentiation. The matched combination of (-)-34 with R)-35 gave one of the four possible diastereomeric pyrone products in 93.1% selectivity. On the other hand, the mismatched pair showed almost no selectivity (Scheme 21) [38]. 

Examples of Dienes and Dienophiles. The synthetic value of D-A reactions can be enhanced in various ways. In addition to hydrocarbon dienes, substituted dienes can be used to introduce functional groups into the products. One example that illustrates the versatility of such reagents is l-methoxy-3-trimethylsiloxy-l,3-butadiene... 

The electron-donating nature of this diene confers high reactivity and orientational specificity in its reaction with unsymmetrical dienophiles.5 This fact, coupled with the readily available conversion to the a,(3-un-saturated ketone from the imparted functionality, makes l-methoxy-3-trimethylsiloxy-1,3-butadiene (2) a potentially very valuable reagent in organic synthesis. The general reaction scheme is illustrated below ... 

B. Preparation of -methoxy-3-trimethylsiloxy-. 3-butadiene. Tri-ethylamine (575 g, 5.7 mol) is stirred mechanically in a three-necked flask (Note 1). To it is added 10.0 g (0.07 mol) of zinc chloride prepared as described above. The mixture is stirred at room temperature under nitrogen for 1 hr. A solution of 250 g (2.50 mol) of 4-methoxy-3-buten-... 

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]. 

PREPARATION AND DIELS-ALDER REACTION OF A HIGHLY NUCLEOPHILIC DIENE fra s-l-METHOXY-3-TRIMETHYLSILOXY-l,3-BUTADIENE... 

Slight modifications of the dienophile or the diene molecule can influence the stereochemical outcome of the reaction substantially. Enone 27, when reacted under thermal conditions with simple dienes produces cycloadducts with diastereoselectivities matching those obtained from 2132. The very similar methyl 2,3,6-trideoxy-x-D-ervt/w-< -hex-2-enopyranoside-4-ulose (28), in the thermal [4 + 2] cycloaddition to ( )-l-methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky s diene, 29), yields adduct 30 in 93% yield and with complete diastereoselectivity33. The adduct has been further converted into (+)-A -acetyldesalanylactinobolin (31)34 ... 

The diastereoselective hetero-Diels Alder reaction of imines leads to enantiomerically pure 2-substituted piperidines, important synthons for the synthesis of nitrogen-containing natural products. 2,3,4,6-Tetra-0-pivaloyl-/ -D-galactopyranosylimines 1, easily synthesized from the respective 1-galactosamine. react with isoprene (2a), 2,3-dimethyl-l,3-butadiene (2b) and ( )-l-methoxy-3-trimethylsiloxy-l,3-butadiene (4) under zinc chloride etherate catalysis71. Adducts 3 are obtained with moderate to good diastereoselectivities, while adduct 5 is produced with a diastereomeric ratio of greater than 95 5. Adduct 5 can then be converted into the alkaloid (S)-anabasin. 

In the latter case, some (118) was also formed. The reaction of 3-thiolen-2-one with 1,3-cyclopentadiene proceeded rapidly at room temperature in the presence of boron trifluoride etherate, to give (119). An exception was the reaction with 1-methoxy-3-C(trimethyls ilyl)oxy]butadiene, which only led to silyl transfer, giving 2-(trimethylsiloxy)thiophen and 4-methoxy-but-3-en-2-one.6 The reaction between the ambient anion of the 5-methyl-2-hydroxy-thiophen system with carbon disulphide and methyl iodide gave (121) in 36% yield, in addition to the expected product (120). Tfie structure of the latter compound was proven by X-ray crystallography, and a reaction path for its formation was suggested. The... 

The reactivity of the 1,4-dioxocin ring toward potential dienophiles (e.g. triazolinediones) has apparently not been explored. The carbaldehyde side chain of 1,4-dioxocin (132 R = CHO) behaves as a dienophile toward l-methoxy-3-trimethylsiloxy-1,3-butadiene, affording dihydropyrone (152) in 25% yield (Scheme 40) oxidation of (152) affords a low yield (5%) of the corresponing pyrone (128) <84AG(E)966>. 

Extension of the [3+4] annulations to more highly oxygenated dienes results in a very effective synthesis of tropones and tro-polones. For example, decomposition of the vinyldiazomethane 4 in the presence of 1-methoxy-l-trimethylsiloxy-1,3-butadiene (46) results in the formation of the cycloheptadiene 47 in 87% yield (Scheme 18). Mild hydrolysis of 47 with citric acid followed by DDQ oxidation results in a very short synthesis of the tropone 48 in 92% yield. The [3+4] annulation with 1-methoxy-l-trimethylsiloxybutadiene is applicable to a range of vinyldiazomethanes, as shown in Table 8. The major limitation is that because of the extremely electron-rich character of the diene, the formation of side products derived from zwit-terionic intermediates dominate over the [3+4] annulation. In general, the side reactions are eliminated by carrying out the reactions in a nonpolar solvent. 

In the presence of 10 mol % Sc(OTf)3, IV-benzylideneaniline reacts with 2-rra s-l-methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky s diene) to afford the corresponding aza Diels-Alder adduct, a tetrahydropyridine derivative, quantitatively (eq 17). On the other hand, in the reaction of M-benzyUdeneaniline with... 

A soln. of l-trimethylsiloxy-l,3-butadiene in tetrahydrofuran added at -78° under argon to a mixture of cinnamaldehyde dimethyl acetal and TiCl4 in dry tetrahydrofuran, and stirred an additional 4 hrs. -> 7-phenyl-5-methoxy-2,6-hepta-dienal. Y 88%. F. e., also in the presence of Ti-alkoxides and with interdiange of the second alkoxy group of the acetal, s. T. Mukaiyama and A. Ishida, Chem. Lett. 1975, 319, 1201. 

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