Allylsilanes 3+2 annulations

The starting materials for annulative cyclization are cycloalkenones that contain the allylsilane side chain in the 4-position. Such starting materials can easily be prepared from vinylogous esters40. Furthermore, reactions of 3-alkoxy-2-cyclohexenones with functionalized iodides in the presence of lithium diisopropylamide provides an excellent route to such precursors41 34 35. 

Stereoselective Ring Annulations by Intramolecular 1,6-Addition of an Allylsilane Function... 

Dienones, such as 4-[4-(trimethylsilyl)-2-butenyl]-3-vinyl-2-cyclohexenone, are useful precursors for these particular transformations the allylsilane side chain is too short for effective 1,4-addition, but just right for 1,6-addition, resulting in six-ring annulation. Three different Lewis acids can be used titanium(IV) chloride, boron trifluoride diethyl ether complex, and ethylaluminum dichloride. The best chemical yields and complete asymmetric inductions were obtained with ethylaluminum dichloride. 

Tricyclic compounds can be obtained directly by annulation on to cyclic allylsilanes, using either ethylaluminum dichloride or titanium(IV) chloride as Lewis acids57. The stereochemical outcome of this particular cyclization is controlled by the relative configuration of the cyclic allylsilane. The reaction follows the usual anti" SE2 process for reactions of allylsilanes with electrophiles. Thus, the reaction was stereospecific, which makes it very useful for stereocon-trolled syntheses of complex ring systems57. 

Substituted (5R,6A,)-6-(dimethyl(phenyl)silyl)-2-phenyldihydropyrazolo[l,2- ][l,2,4]triazole-l,3(2//,5//)-dione 716, synthesized via the [3+2] annulation of a-substituted allylic silanes 715 with PTAD, were oxidized to the corresponding hydroxy substituted urazoles 717. This work shows that allylsilanes with a single substituent at the allylic carbon undergo exclusive stereoselective [3+2] annulation (Scheme 114) <2007TL6671>. 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Exposure ofpara-qmnonc diimine and allylsilane to ZnCl2 in dichloromethane leads to a slow bis-annulation reaction to give the pyrroloindole derivative in which the two silyl groups are traits to each other <20020L953>. The results of optimization studies revealed that the amount and nature of the Lewis acid used and the temperature employed play an important role in determining the course of the reaction (Equation 90). 

As with allylsilanes, increased steric hindrance at silicon favours annulation (equation 105)172 rather than the Sakurai reaction (equations 103 and 104). 

CH2=CHCH2SiMe2(Bu-i) (cf entry 47 of Table 1). Given a similar concern, a new sterically demanding allylsilane, CH2=CHCH2SiMe2(CPh3), has been developed recently as a mild and efficient reagent for hydroxypropyl annulation of electron-deficient alkenes229. 

Another approach leading to pyrrolidine 210 via [3 + 2] cycloaddition is the reaction of A-protected a-amino aldehydes with allylsilanes in the presence of a catalytic amount of BF3 OEt2 (equation 172). No 1,2-silyl group migration occurs in these annulation processes313. 

When chiral allylsilanes are used for coupling with aldehydes, the diastereoselectivity of the reaction depends on the nature of the Lewis acid employed. Chelative SnCU-promoted reaction gives 212 whereas BF3 OEt2 catalyzes the annulation reactions leading to 213 (equation 174)315-317. 

Similar cyclopentane annulations of allylsilanes with benzotropylium salts149,150, tetracyanoethylene151, benzyl cations152 and l,2,4-triazoline-3,5-diones had been reported153. 

The [3 + 2] stereoselective annulations using allylsilanes were also applied to the syntheses of furans (equation 59)156-162 7V-acylpyrrolidines163,164, a 2-thiabicyclo[2.2.1] hept-5-ene-3-spiro-2/-indan-l/-one165 and A2-isoxazoline derivatives166,167. 

The synthesis of polysubstituted tetrahydrofurans was also achieved in a stereoselective manner by a formal [3+2] cycloaddition of an allylsilane with a-triethylsiloxy aldehydes. An example showing the mechanism is illustrated <02JA3608>. In another approach, allylsilane was also allowed to react with a-keto esters in a [3+2] annulation reaction, providing highly substituted tetrahydrofurans in good yields as single diastereomers <02OL2945>. 

Micalizio, G.C., and Roush, W.R. 2001. Studies on file synthesis of pectenotoxin II synthesis of a C(Zingone et al. 2006)-C(Pavela-Vrancic et al. 2001) fragment precursor via [3 + 2]-annulation reactions of chiral allylsilanes. OrgLett 3,1949-1952. 

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. 

Hie regioselective cycloadditions can generate useful synthetic intermediates. Conversion of adduct (n9) to (120) provides the equivalent of an a-phenylcyclopentanone annulation (equation 124). Hie allylsilane moiety generated by the bis(silyl) acetate (113) is a useful entity. For example, the cycloadduct (121) can be easily transformed to (122), which is a regioisomer of the adduct resulting from reaction with (112 R = OAc) (equation 125). ... 

Snp2 seems unique for this annulation. After generation of the allylstannane, the Sn" serves as a Lewis acid catalyst and provides internal chelation. The fluoride counter ion is an ideal nucleophile for the activation of the allylsilane. The high stereoselectivity (25 1 to 75 1) is attributed to chelation (Eq. 2) [12]. 

A novel variant of the Stork-Jung modified Robinson annulation was developed and applied to the formal total synthesis of (+)-guanacastepene A by the research group of B.B. Snider. Instead of using MVK directly, they prepared the necessary 1,5-diketone by alkylating the ketone with an allylsilane and generating the ketone functionality via a Fleming-Tamao oxidation. 

Organ, M. G., Dragan, V., Miller, M., Froese, R. D. J., Goddard, J. D. Sakurai Addition and Ring Annulation of Aiiyisiianes with a, 3-Unsaturated Esters. Experimental Results and ab Initio Theoretical Predictions Examining Allylsilane Reactivity. J. Org. Chem. 2000, 65, 3666-3678. 

In the presence of Mn(OAc)3- 2ll,() in AcOH, allyltrimethylsilane reacts with 1,3-diketones and /I-ketoesters to give trisubstituted dihydrofurans in good to high yield (Scheme 10.187) [502], Mn(OAc) j serves as an oxidizing agent to generate an electrophilic carbon radical intermediate from the substrate. It is probable that annulation of the carbon radical with the allylsilane followed by oxidation with another equivalent of Mn(III) forms the silicon-containing cyclic products. 

The reaction of acetals and ketals with enol silyl ethers, usually catalyzed with the more traditional Lewis acids such as boron trifluoride etherate or titanium tetrachloride, can be carried out with trimethylsilyl triflate catalysis50. In the example shown in equation 42 the resulting allylsilane was annulated with titanium tetrachloride. 

The annulation involving an atth-allylsilane 102 is less sensitive to the nature of the R group and a 5-2,6-DHPs 103 are obtained selectively. Noteworthy, bulky R substituent allowed high yield and diastereoselectivity (Scheme 49) (2011OL4652). 

Panek s synthesis is highUghted by the efficient construction of a cis-and trans-2,6-disubstituted tetrahydropyran ring. As described in Sect. 2.4, Panek s annulation between aldehydes and chiral allylsilanes can be regarded as a Hosomi-Sakurai-Prins reaction, in which the stereochemistry of cis-... 

Racemic allylsilane 175 has been efficiently resolved through reaction ([3+2] annulation) with the chiral pyravate 176, made from (R)-pantolactone [94]. The product of the [3+2] annulation was obtained in 45% yield, as a single diastereomer 177. Reduction of 177 with LiAlH afforded the diol (—)-178 in >99% ee. The unreacted aUylsilane (—)-175 was recovered in 24% yield and high ee. Treatment of (—)-175 with methyl pyruvate followed by LiAlH4 reduction afforded (+)-178 in > 99% ee. It is worth to note that as both enantiomers of pantolactone are commercially available and inexpensive, this KR process gives access to both enantiomers of aUysilane 175. 

Alkenyl Fischer carbene complexes, (OC)5Cr=C(OMe)CH=CHPh, undergo mild insertion reactions with organosilanes to give allylsilanes, Et3SiCH(OMe)CH=CHPh in good yield. si The fluorovinyl carbene complex Cr(CO)5 =C(OMe)CF=CF(Bu") (106) reacts with PhCsCPh by an annulation/defluorination process to form a monofluorobenzene.382... 

We then prepared trienone 2, a substrate with three electrophilic sites (Eq. 5). In addition to the possibility of 1,2-addition, 5 might react with the allylsilane moiety in either 1,4- or 1,6-fashion to annulate a cyclopentane or cycloheptane ring, respectively (cf. 6 and 2). The chemistry of trienone 2 proved intriguing. Treatment of 5 with ethylaluminum dichloridel2 gave the 6-7 fused bicyclic enone in 55% yield, uncontaminated by other products. In contrast, treatment of 5 with fluoride ion produced hydrindanone 2 in 45% yield, accompanied by 5% of a bicyclic tertiary alcohol resulting from 1,2-addition. 

The intramolecular addition of unsymmetrical allylsilanes to conjugated dienones is a preparatively useful means for annulating cyclohexane rings. 

Cyclohexane formation is not restricted to 1,6-addition of an allylsilane to a dienone. Equation 10 contains two examples whereby a lengthy tether linking the reactive functionalities leads to cyclohexane annulation via 1,4-conjugate addition. 

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