A Mechanistic Switch from Homoallylation to Cyclopropylcarbinylation of Aldehydes

Abstract

Cyclopropanated allylboration reagents participate in homoallylation reactions of aliphatic and aromatic aldehydes, generating allylicsubstituted alkenes that are difficult to produce via other methods. In studying the effect of cyclopropane substituents, we discovered that an aryl substituent completely changes the outcome to cyclopropylcarbinylation, as if the cyclopropylcarbinyl fragment were transferred intact. However, density functional theory computation suggested a novel mechanism involving ring opening and reclosure, which is supported by experimental evidence.

Homoallylboration of Aldehydes: Stereoselective Synthesis of Allylic-Substituted Alkenes and E-Alkenes

“…This difference in reactivity is not due to a sterics, as even bulkier cyclohexyl and t -butyl derivatives reacted in the usual S E 2′ fashion ( 29 , 30 ; see Scheme ). Computational and experimental mechanistic studies support a surprising mechanism that is reported in the subsequent manuscript …”

“…We first sought to test the effect of varied substituents in the boronate α-position. These substrates have been prepared via Aggarwal's lithiation-borylation method (Scheme 2), in which carbenoids derived from deprotonation of alkyl carbamates or benzoates 10 are inserted into the B−C bond of cyclopropyl B(pin) (11). 5 Consistent with Aggarwal's findings, insertion of more hindered carbenoids (R = i-Pr and t-Bu) requires the use of benzoate rather than carbamate derivatives.…”

“…Computational and experimental mechanistic studies support a surprising mechanism that is reported in the subsequent manuscript. 11 In summary, we have developed versatile methods for preparation of boronates with a wide variety of αand γsubstituents. These boron reagents undergo homoallylation with aliphatic and aromatic aldehydes and stereoselectively generate substituted bishomoallylic alcohols with stereochemistry that is consistent with Zimmerman−Traxler models.…”

Enantioenriched BoronC,N‐Chelates via Chirality Transfer

“…Additional references cited in the Supporting Information. [9,20,25,42,59,[65][66][67][68][69][70][71][72][73][74][75][76][77] Deposition Numbers 2249555 (for 16 e), 2235885 (for 16 i) and 2235887 (for 18 a) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.…”