Aldehydes reactions with allenylsilanes

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. 

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. 

Allenylsilanes react with acetals to afford homopropargylic ethers (Table 9.37) [61]. These reactions are promoted by silyl and carbocation species. A variation of this conversion involves in situ formation of the acetal from an aldehyde and Me3SiOMe (Eq. 9.55). The success of this method indicates that conversion of the aldehyde to the acetal and its subsequent reaction with the silane must be faster than direct reaction of the aldehyde with the silane. 

The reaction of trimethylsilylallenes with aldehydes and ketones in the presence of titanium tetrachloride provides a regiocontrolled route to homopropargylic alcohols of a variety of substitution types. Thus, the addition of 1-alkyl-substituted trimethylsilylallenes to carbonyl compounds furnishes the desired alkynes directly, whereas reactions involving allenylsilanes initially produce mixtures of alkynes... 

Allenylsilanes also undergo formal [3 + 2] cycloaddition reactions with enones, aldehydes, iminium species generated in situy and acid chlorides to give a variety of five-membered products (Scheme 3-111). The reaction is considered to proceed through stepwise mechanisms. The [3 + 2] cycloaddition reaction can be performed in an enatioselective manner by using the chiral scandium catalyst. 

Allenylsilanes undergo intramolecular additions to appropriately positioned aldehydes, imines, conjugated esters and alkenes to afford various alkynylcyclopentane and cyclohexane derivatives (Eqs. 9.66-9.70) [66]. The reactions are promoted by SnCl4 or by thermolysis. The stereochemistry of these cyclization reactions is consistent with a concerted sigmatropic process as illustrated in Scheme 9.17. 

As discussed previously [33-36], the Lewis acid-mediated reaction of 1,2-alleny] silanes with aldehydes or ketones can also afford homopropargylic alcohols 75 or five-membered 2,3-dihydrofurans 76 [37]. The type of reaction depends on the structure of the allenylsilanes, the substituent of the silyl group and the reaction conditions. 

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%. 

The Lewis acid-promoted reaction of aldehydes with a-substituted allylsilanes forms 3-silyltetrahydrofurans in good to high yields.169-172 The use of homochiral allylsilanes is very valuable for highly diastereo- and enantio-selective syntheses of tri- and tetrasubstituted tetrahydrofurans (Equation (43)). Catalytic asymmetric [3-1-21-cycloaddition of a-substituted allenylsilanes to aldehydes can be achieved by a chiral scandium complex.173... 

Allenylsilanes and -stannanes combined with a titanium salt are versatile reagents for propargylation of aldehydes (Eq. 115) [297], ketones (Eq. 116) [298], (A,0)-acetals (Eq. 117) [299], and a,/ -unsaturated ketones in a conjugate fashion (Eq. 118) [300]. Intramolecular reaction has also been reported (Eq. 119) [301] in which a Bu3Sn-carbon bond was cleaved exclusively in the presence of a TBS-carbon bond. That the isomeric starting material, propargylstannane, did not give the desired product (Eq. 120) demonstrates that the direct scission of the carbon-Sn bond by the electrophile under these reaction conditions is not a feasible path [301]. 

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. 

Research in the laboratory of R.L. Danheiser has shown that allenylsilanes can be reacted with electrophiles other than enones, such as aldehydes and A/-acyl iminium ions to generate oxygen and nitrogen heterocycles." Aldehydes can function as heteroallenophiles and the reaction of C3 substituted allenylsilane with the achiral cyclohexane carbaldehyde afforded predominantly c/s-substituted dihydrofurans. 

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... 

Allenylsilanes react with acetals, as they do with aldehydes, by addition, but a simple elimination step completes the substitution reaction (Scheme 48). Propargylsilanes likewise react with acetals in the presence of Lewis acids (Scheme 49). The reaction has en used intramolecularly (Scheme 50), where the first step is likely to be acetal or hemiacetal formation followed by ring closure, and in reactions at the anomeric position of sugars with high levels of axial attack giving allenes. ... 

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. 

In reactions of a C-3 substituted allenylsilane with achiral aldehydes, cis-substituted dihydrofurans are the predominant products (eq 11). ... 

Homopropargylic and allenic alcohols are formed from the reaction of propargylsilanes and allenylsilanes, prepared through trichlorosilylation, with aldehydes (eqs 18 and 19). ... 

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