Applications of Allenylsilanes in Organic Synthesis

Introduction

Allenylsilanes 2 are versatile reagents widely used in organic synthesis.[1] Generally, allenylsilanes react as propargyl anion equivalents in Lewis acid mediated[2] or thermal[3] nucleophilic addition to electrophiles such as carbonyls, imines, Selectfluor, and N-bromosuccinimide, etc.[1] [4] [5] The regiospecific addition of allenylsilanes provides a β-vinyl cation, which is stabilized by a C–Si bond, which is called β effect. The C–Si bond in allenylsilanes is oriented cis-coplanar to the p-orbital of the carbocation and provides direct stabilization.[5] Allenylsilanes undergo [3+2] annulations with α,β-unsaturated carbonyls, carbonyl compounds, imines, and nitrosyl cations to form cyclo-pentenones, dihydrofurans, dihydropyrroles, and isoxazoles, respectively.[1] [4] [5]

The efficient methods for the synthesis of allenylsilanes 2 are copper-mediated 1,3-substitution reactions of carbon nucleophiles to propargylic substrates 1 having a leaving group at the propargylic position.[6] [7]

Scheme 1 Synthesis of allenylsilanes

Abstracts

(A) Reactions with Aldehydes: Allenylsilanes react with aldehydes and ketones in the presence of titanium tetrachloride to provide homopropargylic alcohols in a regioselective manner. The reaction of chiral allenylsilanes with chiral aldehydes leads to the formation of mainly syn homopropargylic alcohols.[3] The reaction of chiral 3,3-disubstituted allenylsilane 3 with paraformaldehyde in the presence of TiCl4·2THF generates chiral homopropargylic alcohol 4, which is the key intermediate in the total synthesis of (–)-histrionicotoxin 5.[8]
(B) Reactions with Aldehydes: The reaction of chiral 2-silyl-substituted α-allenic alcohol 7 with aldehyde 6 in the presence of InBr3 give rise to chiral homopropargylic alcohol 11. The reaction proceeds via formation of oxocarbenium ion 8, which undergoes a [3,3]-sigmatropic rearrangement to form the alcohol 11. The alcohol 11 is the key intermediate in the total synthesis of the natural product (+)-neopeltolide 12.[9]
(C) Reactions with Aldehydes: The addition of γ-trimethylsilyl allene esters 13 to aldehydes 14 in the presence of i-PrOLi leads to the formation of regiospecific γ-carbinols 18. The addition of anionic catalyst i-PrOLi leads to the intermediate 15, which possess enolate-like reactivity. The nucleophilic addition of intermediate 15 to aldehyde 14 generates intermediate 16. Then, the silyl group undergoes a 1,3-shift and the nucleophile eliminates to form the intermediate 17. This reaction is the key step in the total synthesis of the [3.2.1] bicyclic natural product vitisinol D.[10]
(D) Reactions with Imines: The enantioenriched allenylsilane 20 reacts with the in situ generated iminium ion generated from t-butyl carbamate 22 and aldehydes 21 in the presence of BF3·OEt2 to form substituted 4,5-dihydropyrroles 24. Similarly, the reaction of allenylsilane 20 with an iminium ion, generated in situ from methyl carbamate 23 and aldehydes 21 in the presence of TMSOTf, forms substituted 4,5-dihyrooxazines 25.[11]
(E) Gold-Catalyzed Cycloisomerization: In the presence of AuCl3 the γ-silyl-substituted allenyl ketones 29 undergoes cycloisomerization to 3-silyl furans 32. The cyclization of the allenyl ketone 29 give rise to the intermediate gold-carbene 31, and upon the 1,2-Si shift, the 3-silyl furan 32 is produced.[12]
(F) The Pauson–Khand Reaction of 1,1-Disubstituted Allenylsilanes: The Pauson–Khand reaction of 1,1-disubstituted allenylsilanes with terminal alkynes leads to 4-alkylidene-2-cyclopenten-1-ones in good yields. The reaction proceeds through a [2+2+1] pathway. A three-membered iron metacycle is generated by reaction of allenylsilane 33 with diiron nonacarbonyl. The iron metacycle undergoes complexation with alkyne 34, and finally, a reductive elimination takes place to provide the 4-alkylidene-2-cyclopenten-1-one 35.[13]
(G) [2+2+2] Cycloaddition with Benzynes: Benzynes possess a strained triple bond and are highly electrophilic. Allenylsilanes 37 react with two equivalents of benzynes 36 to generate (α-phenanthrenyl)vinylsilanes 38 in excellent yields. The reaction proceeds through a [2+2+2] pathway.[14]

• References

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