Sakurai reaction

The Sakurai reaction (also known as the Hosomi-Sakurai reaction) is the chemical reaction of carbon electrophiles (such as a ketone shown here) with allylic silanes catalyzed by strong Lewis acids. [1][2][3][4][5][6] It is named after the chemists Akira Hosomi and Hideki Sakurai.

Lewis acid activation is essential for complete reaction. Strong Lewis acids such as titanium tetrachloride, boron trifluoride, tin tetrachloride, and AlCl(Et)2 are all effective in promoting the Hosomi reaction. The reaction is a type of electrophilic allyl shift with formation of an intermediate beta-silyl carbocation. Driving force is the stabilization of said carbocation by the beta-silicon effect.

The reaction has been applied in a Sakurai-Prins-Ritter multicomponent reaction with in step two a Prins reaction and in step three a Ritter reaction [7][8]:

Contents

Various Reactions

The Hosomi-Sakurai reaction can be performed on a number of functional groups. An electrophilic carbon, activated by a Lewis Acid, is required. Below is a list of three different functional groups that can be used in the Hosomi-Sakurai reaction.

Mechanism

The proposed mechanism for the Hosomi-Sakurai reaction using a ketone is displayed above. The mechanisms for all Hosomi-Sakurai reactions follow the same general principle where a strong Lewis Acid activates an electrophilic carbon, which then undergoes nucleophilic attack from electrons on the allylic silane.

β-Silicon Effect Stabilization

As displayed in the mechanism, the Hosomi-Sakurai reaction goes through a secondary carbocation intermediate. Secondary carbonations are inherently unstable, however the β-silicon effect from the silicon atom stabilizes the carbocation. Silicon is able to donate into an empty p-orbital, and the silicon orbital is shared between the two carbons. This stabilizes the positive charge over 3 orbitals. Another term for the β-silicon effect is silicon-hyperconjugation. This interaction is essential for the reaction to go to completion.

See also

References

  1. ^ Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 1295.
  2. ^ Hosomi, A. et al. Chem. Letters 1976, 941.
  3. ^ Hosomi, A. et al. J. Am. Chem. Soc. 1977, 1977, 99, 1673.
  4. ^ Hosomi, A. Acc. Chem. Res. 1988, 21, 200-206. (Review)
  5. ^ Fleming, I. et al. Org. React. 1989, 37, 57-575. (Review)
  6. ^ Fleming, I. Comp. Org. Syn. 1991, 2, 563-593. (Review)
  7. ^ A Sakurai-Prins-Ritter Sequence for the Three-Component Diastereoselective Synthesis of 4-Amino Tetrahydropyrans Oleg L. Epstein and Tomislav Rovis J. Am. Chem. Soc.; 2006; 128(51) pp 16480 - 16481; (Communication) doi:10.1021/ja066794k
  8. ^ In this sequence the dioxane 1 is activated by Lewis acid trimethylsilyl triflate as the reactive intermediate 2. This oxonium ion reacts in a Hosomi-Sakurai reaction with allyltrimethylsilane forming intermediate product 3 which is again activated this time by triflic acid to shortlived oxonium intermediate 4 and a Prins reaction follows to 5 whereby the transient carbocation is captured first by acetonitrile and then by water in a Ritter reaction. In this sketch R is a cyclohexyl group and t-Bu a tert-butyl group

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