In spite of their highly selective nature, a clear disadvantage of Type I allylations is the difficulty often encountered in synthesising crotylmetals and other substituted allylmetals with defined olefin geometry. This is less of a problem with the more stable Type II reagents, which tend to provide syn products from both (E)- and (Z)- starting materials. Type II reagents include allylsilanes and allylstannanes (in this article we will focus on allylsilanes). Whereas allylations involving allylboron reagents are examples of Type I allylations, the Hosomi–Sakurai reaction is an example of a Type II allylation.[1,2,3]
The Hosomi–Sakurai Reaction is an Example of Type II Allylation
Allylsilanes are relatively poor nucleophiles and therefore require external Lewis acid activation to increase the electrophilicity of the aldehyde (or ketone). As a consequence, the reaction of this type of nucleophile proceeds via an open, acyclic transition state that is poorly defined when compared with the chair-like transition state adopted by Type I reagents.
The first stage of the Hosomi-Sakurai reaction, or nucleophilic addition of an allyltrialkylsilane onto an aldehyde, involves activation of the carbonyl group by a Brønsted- or Lewis acid. Attack on the activated electrophile by the π-system of the allylsilane then follows to generate a carbocationic intermediate. This intermediate is extremely short-lived and is neutralised by β-elimination of the silyl moiety to regenerate a carbon-carbon double-bond. A silyl group is a good electrofuge and irreversible elimination generally occurs before any other pathway can take place. The reaction is highly selective for the SE2’ product since
nucleophilic attack occurs exclusively from the γ-position as not only is this site generally less hindered, but the positive charge in the transition state is also stabilised as it positioned β- to the silicon atom. There is also a larger coefficient in the HOMO at the γ-carbon.
Reactivity Arises from the “β-Effect” of Silicon
The reactivity of allylsilanes arises from the “β-effect” of silicon. Silicon can stabilise a carbocation at the β-position, as the σC-Si of a silylmethylene group can efficiently overlap with the empty p orbital, lowering the energy of the system. In the analogous system where a carbocation is positioned β- to a carbon atom, the σC-C is further in energy from the empty p-orbitals, resulting in less efficient overlap and thus less stabilisation. Maximum hyperconjugation is achieved when the Si-C bond is aligned parallel to the adjacent p orbital.
Achieving Enantioselectivity
There are a number of ways in which the stereocentres created in the Hosomi–Sakurai reaction can be controlled. Stereochemical information embedded within a chiral aldehyde or allylsilane can be transmitted into the homallylic alcohol product by way of a substrate-controlled process. Alternatively, the use of chiral Lewis acids or chiral oxocarbenium ion precursors can produce stereodefined products inasymmetric reagent-controlled reactions and auxiliary-controlled reactions.
Conclusion
The Hosomi-Sakurai reaction, an important method in organic synthesis, involves the addition of a silyl group to a carbonyl compound. The reaction is catalyzed by Lewis acids, typically titanium or tin compounds. The reaction proceeds through the formation of an oxocarbenium ion intermediate, which undergoes nucleophilic attack from the γ-carbon of the allylsilyl group. The reaction relies on the "β-effect” of silicon, in which a positive charge at the β-position of a silane compound is stabililzed. This versatile reaction is widely used in the synthesis of various organic compounds, especially in the creation of complex molecules with diverse functionalities.
References
Hosomi, A. "Characteristics in the reactions of allylsilanes and their applications to versatile synthetic equivalents". Acc. Chem. Res. 1988, 21, 200–206. doi:10.1021/ar00149a004
Sakurai, H.; Hosomi, A.; Kumada, M. "Addition of trichloromethyl radicals to alkenylsilanes". J. Org. Chem. 1969, 36, 1764–1768. doi:10.1021/jo01258a052
Hosomi, A.; Sakurai, H. "Syntheses of γ,δ-unsaturated alcohols from allylsilanes and carbonyl compounds in the presence of titanium tetrachloride". Tetrahedron Lett. 1976, 17, 1295–1298.
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