Tandem with allylsilanes

Apart from the tandem metathesis/carbonyl o[efination reaction mediated by the Tebbe reagent (Section 3.2.4.2), few examples of the use of stoichiometric amounts of Schrock-type carbene complexes have been reported. A stoichiometric variant of cross metathesis has been described by Takeda in 1998 [634]. Titanium carbene complexes, generated in situ from dithioacetals, Cp2TiCl2, magnesium, and triethylphosphite (see Experimental Procedures 3.2.2 and 3.2.6), were found to undergo stoichiometric cross-metathesis reactions with allylsilanes [634]. The scope of this reaction remains to be explored. 

Tandem acetalization-allylation reaction of aldehydes with allylsilanes provides a convenient route to homoallyl ethers.82 Under catalysis by Sc(OTf)3, various aldehydes can be converted into homoallyl ethers by treatment with... 

Finally, a recent study by Majetich and Hull has demonstrated the feasibility of the carbanion-accel-erated divinylcyclobutane rearrangement. Whereas the thermal rearrangement of the divinylcyclobu-tane (273 Scheme 38) required extended heating at 180 C and proceeded in modest yield, the corresponding enolate was shown to rearrange smoothly at -35 C in 90% yield. As illustrated in Scheme 39, the enolate-accelerated DVCB rearrangement can be employed in tandem with the intramolecular fluoride-promoted Michael addition of allylsilanes to provide an attractive route to a variety of fused bi-cyclic cyclooctane derivatives. 

Discussion The obtained aldehydes with an allylsilane moiety are useful intermediates among others for the tandem Knoevenagel allylsilane cyclizationl l. This domino reactions ] allows e.g. the stereoselective formation of l,2-tran5-substituted cyclopentanes transicis = 99.6 0.4). 

Olefin metathesis. Cross metathesis permits a facile access to allylsilanes and Z)-a,P-unsaturated nitriles. Furthermore, employing an alkene metathesis in tandem with asymmetric allylboration provides functionalized alkenes. ... 

In the presence of BF3-OEt2, allyldimethylsilyl enolates react with acetals to give allylated 1,3-diol monoethers.139 A similar tandem aldol-allylation reaction can be performed by strained allylsilyl enolates such as 26 without promoter (Equation (34)).140 Allylsilanes bearing a vinyl ether moiety at the /3-position give rise to another type of tandem aldol-allylation reaction in the presence of a Lewis acid.141... 

An additional advantage of the intramolecular protocol stems from the opportunity to prepare easily the required polyfunctional precursors via cobalt carbonyl stabilized propargyl cations. The approach based on the tandem utilization of Co-mediated alkylation and Pauson-Khand annulation was developed in Schreiber s studies to elaborate short pathways for the synthesis of polycyclic compounds. An example of the efficiency of this protocol is the two-step transformation of the acyclic precursor 409 into the tricyclic derivative 410. The cobalt-complexed acetal 409 was first transformed into the cyclooctyne derivative 411 via intramolecular reaction of the in situ generated propargyl cation 409a with the allylsilane moiety. Cyclooctyne 411 underwent smooth cycloaddition in the presence of carbon monoxide to give the target compound 410 with excellent stereoselectivity. 

Intramolecular reaction of an allylsilane and an aldehyde was performed to prepare cyclic compounds as illustrated in Eq. (90) [233], which shows a high diastereoselec-tivity. The cyclization of optically active allylsilane proceeds stereoselectively in a manner consistent with the antiS l mechanism (Eq. 91) [234]. Development of a new reagent with a bis-allylsilane moiety effected tandem inter- and intramolecular cyclizations to give cyclic compounds as exemplified in Eqs (92) [235] and (93) [236-238]. In Eq. (92), the double addition product initially formed underwent a pinacol-type rearrangement under the influence of TiCU to give, eventually, the methyl cyclopentyl ketone. Further examples of intramolecular cyclization of allylsilanes are summarized in Table 8. 

The tandem Mukaiyama aidoi reaction-Prins cyciization was utilized during the formal total synthesis of leucascandrolide A by S.D Rychnovsky. The addition of the activated aldehyde to the enol ether resulted in the formation of an oxocarbenium ion, which was captured intramolecularly by the allylsilane moiety to form a new tetrahydropyran ring. The reduction of the crude reaction mixture with NaBH4 was performed to remove the unreacted aldehyde starting material, thereby facilitating the chromatographic purification of the product. The product was isolated as a 5.5 1 mixture of epimers at C9. 

In the presence of excess acetyl halide and a tin(II) catalyst aromatic acetals react with allyltrimethylsilane to give a-allylbenzyl halides in good yield by double substitution of the acetal alkoxy groups (Scheme 10.127) [365]. The indium-catalyzed tandem reaction using a hydrosilane-allylsilane system enables deoxygenative allylation of aromatic ketones [366]. 

Butyn-2-one undergoes tandem [3+2] cycloadditions of allyltriisopropylsilane to give a bicyclo[3.3.0]octane as a mixture of three possible diastereomers in a good yield (Scheme 10.169) [468]. The use of a reduced amount of the allylsilane forms a silylated cyclopentene as a minor product. This indicates that the 1 1 cycloadduct is the precursor of the bicyclic product. In contrast, the ZnL or Me2AlCl-promoted reaction of 3-butyn-2-one with an isocyclic allyltrimethylsilane affords a [2+2] adduct wifhout [3+2] adducts [448a, 469] (vide infra). 

Allylsilanes are good acceptors of 1,3-dipolar compounds such as nitrones [503] and oxyallyl cations [504]. West et al. have used allylsilanes to trap oxyallyl cations generated during the Nazarov cyclization of l,4-dien-3-ones (Scheme 10.188). The tandem bicyclization provides bicyclo[2.2.1]heptanes with high diastereoselectivity. 

Schinzer and Langkopf (83) reported in 1994 their synthesis of various seven- and eight-membered iV-heterocyclic systems resembling the benza-zepine framework of cephalotaxine (Scheme 49) by means of tandem Beckmann rearrangement-allylsilane cyclization. Treatment of compounds 286 and 287 with diisobutylaluminum hydride yielded the heterocycles 288 and 289, respectively. [See Note Added in Proof, p. 264.]... 

In addition to their use in Mannich (and variant) reactions, iminium ions are useful for other cationic type cyclizations. Corey employed a novel tandem iminium ion cyclization as part of an elegant cascade used for the synthesis of aspidophytine. The reaction of tryptamine 292 and dialdehyde 293 in CH3CN at ambient temperature afforded the pentacyclic skeleton of the alkaloid (296 Scheme 54) (99JA6771). Condensation of the free amino functionality of 292 with the dialdehyde produced a dihydropyridinium intermediate 294 that then cyclized onto the indole n-bond to give 295. The iminium ion so produced underwent a second cyclization with the tethered allylsilane moiety to give 296. Protonation of the enamine in 296 provided still another iminium ion (297) that was then reduced with NaCNBH3 to furnish 298 in 66% yield. All of the above reactions could be made to occur in a single pot. 

An intriguing tandem -acyliminium process occurs when allylsilane reacts with A/,A -bis(alkoxy-alkyl)amides under the influence of TiCU (equation 53). The initially formed substitution product cy-ciizes after generation of a second A(-acyliminium ion in an addition process with chloride acting as nucleophile. 

An interesting application of allylsilane as ir-nucleophile is the tandem N-acyliminium coupling with dimethoxycarbamate (139). Piperidine derivative (140) is obtained as a mixture of diastereoisomers (equation 103). ... 

Intramolecular substitutions involving an allylsilane moiety as well as following a metallo-ene reaction pattern have been reported. Tandem metallo-ene cyclization and vinylstannane coupling serve to construct cycloalkanes with vicinal alkenyl chains. " ... 

Treatment of the oxime 6>-mesylate 13 with DIBAL resulted in the formation of the tricyclic benz-3-azepine 14 in a stereoselective tandem Beckmann rearrangement / allylsilane cyclisation <97SL632>. Treatment of ketoximes with divinylketone or its equivalents affords mixtures of the bridged heterocycles 15 and 16 <97TL6099>. In most cases formation of the 7-membered ring predominates, particularly in polar solvents. 

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

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