Synthesis reaction with allenylsilanes

Allenyls-9-BBN required for the synthesis of these unsaturated compounds are obtained by the following reaction sequence. Allenylsilanes [6] are lithi-ated with tert-butyllithium [7], followed by treatment with B-OMe-9-BBN and... 

The synthesis of propargylsilanes has also been thoroughly explored, and these useful reagents are readily prepared by the addition of substituted lithioacetylides to Me3SiCH2l. Propargylsilanes have subsequently been used in titanium(IV) chloride-promoted reactions with acetals to yield functionalized Q -allenylsilanes or functionalized alkenes. 

Synthesis of Azulenes. Reaction of tropylium cations with allenylsilanes produces substituted azulenes. Typically, commercially available tropylium tetrafluoroborate (2 equiv) is ert5)loyed. The second equivalent dehydrogenates the dihydroazu-lene intermediate to produce the aromatic product. Poly(4-vinyl-P3Tidine) (poly (4-VP)) or methyltrimethoxysilane is used to scavenge the HBF4 produced in the reaction. 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

The catalytic reaction giving allenes by the addition of a hydrosilane twice to 1,3-diynes65 has been applied to the asymmetric synthesis of axially chiral allenylsilanes although the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (23, 43 )-PPM is the best catalyst for the addition of phenyldimethyl-silane to diyne 52 giving allene 53 with 22% ee (Scheme 14).66 663... 

Jin and Weinreb reported the enantioselective total synthesis of 5,11-methano-morphanthridine Amaryllidaceae alkaloids via ethynylation of a chiral aldehyde followed by allenylsilane cyclization (Scheme 4.6) [10]. Addition of ethynylmagnesium bromide to 27 produced a 2 1 mixture of (S)- and (R)-propargyl alcohols 28. Both of these isomers were separately converted into the desired same acetate 28 by acetylation or Mitsunobu inversion reaction. After the reaction of 28 with a silyl cuprate, the resulting allene 29 was then converted into (-)-coccinine 31 via an allenylsilane cyclization. 

The allenylsilanes are excellent nucleophiles and they can react with a variety of electrophilic species in annulation processes that provide access to diverse products. Allenylsilane 112 (Eq. 13.36) reacts with tropylium fluoroborate 111 to provide azu-lene 113 [35]. The reaction is slow and it is necessary to use an acid scavenger so as to inhibit protiodesilylation by the fluoroboric acid that is generated during the course of the annulation. The excess tropylium salt abstracts a hydride from the reaction intermediate leading to the azulene. There are relatively few direct methods for the synthesis of azulenes. 

Allenylsilanes 159 (Eq. 13.53) and 161 (Eq. 13.54) differ in the axial stereochemistry of the allene function. In each case, formation of the benzyl imine, followed either by treatment with tin(IV) chloride in benzene at room temperature or heating in toluene, leads to diastereomeric products 160 and 162 [63], Significantly, there is no crossover, pointing to a concerted (or fast, stepwise) process. Since the absolute stereochemistry of the allenylsilanes is easily controlled, the methodology is ideal for applications in total synthesis. Weinreb and co-workers have used the reaction for his synthesis of the marine natural product (-)-papuamine. 

The allenylsilane ene reaction is also well suited for the synthesis of cyclohexane rings. Jin and Weinreb have described the process of Eq. 13.55 in a synthesis of 5,11-methanomorphanthridine, an Amaryllidaceae alkaloid [64], Conversion of aldehyde 163 to imine 164 with piperonylamine took place in situ. Heating the solution of imine at reflux in mesitylene for 2 h led to cyclization through the conformer shown. The yield of 165 from aldehyde 163 was 66%. 

Reactions of chiral allenes proceed with a preference for the formation of the syn diastereomer. The stereochemical outcome of these reactions can be rationalized by invoking an open transition state model for the addition reactions (Figure 12), which depicts an antiperiplanar orientation of the chiral allenylsi-lane to the aldehyde carbonyl. In this model, steric repulsion between the allenyl methyl and the aldehyde substituent is most likely responsible for the destabilization of transition state (B), which leads to the anti (minor) stereoisomer. This destabilizing interaction is minimized in transition state (A). Table 5 illustrates representative examples and summarizes the scope of the regiocontrolled synthesis of homopropargylic alcohols using allenylsilanes. 

Intramolecular imino ene reaction of an allenylsilane has recently been found to generate cyclohexyl systems with adjacent cis-amino and -alkynyl moieties. This enantioselective ene cyclization was developed for the enantio-selective total syntheses of (—)-montanine (338), (-)-coccinine (351), (-)-pancracine (339), and (-)-brunsvigine (356) (a formal total synthesis) by the same research group (181) (Schemes 40 and 41). A precursor allenylsilane-aldehyde 370 for the enantioselective ene cyclization was synthesized from scalemic epoxy alcohol 369 in nine steps. The allenylsilane-aldehyde 370 thus obtained reacted with A -triphenylphosphinyl-(2-bromo-4,5-methy-lenedioxy)phenylmethylimine in boiling mesitylene to lead to a cyclized product 371 in 63% yield after protodesilylation. Hydrogenation of 371... 

Synthesis of 1,3-Dibydrofurans. (f-Butyldimethylsilyl)-allenes combine with aldehydes to produce dihydrofurans (eq 10). In a typical reaction, the aldehyde and 1.1 equiv of titanium tetrachloride are premixed at —78 °C in methylene chloride for 10 min. The allenylsilane (1.2 equiv) is then added, and the reaction mixture is stirred in the cold for 15—45 min. 

The azulene synthesis proceeds best with 1,3-dialkyl (t-butyldimethylsilyl)allenes. (Trimethylsilyl)allenes desilylate to generate propargyl-substituted cycloheptatrienes as significant byproducts. As observed in the other [3 + 2] annulations discussed already, allenylsilanes lacking C-1 alkyl substituents do not participate in the reaction. 

The Sn2 reaction of propargyl tosylates with trimethylsilyl-methylmagnesium chloride in the presence of a stoichiometric amount of CuCN-2LiCl permits the large-scale synthesis of allenylsilanes (eq 24). ... 

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