Enantioselective Petasis borono–Mannich reactions in the syntheses of chiral homoallylic amines, allenes and 1,4-dienes
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The Petasis borono-Mannich reaction is a multicomponent condensation reaction of amines, carbonyl compounds, and boronic acids or esters to generate valuable building blocks for synthesis. Asymmetric Petasis reactions have been achieved using ligand exchange between boronic esters and chiral biphenol catalysts, providing access to optically enriched products including chiral homoallylic amines, allenes and 1,4-dienes. An asymmetric Petasis allylation reaction has been developed for the expedient, modular synthesis of enantioenriched homoallylic amines. The reaction conditions tolerate aldehydes and amines possessing electronic and steric properties unaccessible to this point, notably including challenging aliphatic substrates. This method was used in a diastereoselective Petasis crotylation, providing access to both syn- and anti- products in good yields and with excellent selectivities. A new chiral biphenol catalyst was designed and synthesized in order to promote an asymmetric traceless Petasis reaction with sulfonyl hydrazides, glycolaldehyde and alkynyl boronates. The transient propargylic hydrazide underwent retro-ene rearrangement, resulting in a stereospecific point-to-axial chirality transfer generating the enantio-enriched allene products. A complementary methodology was devised by employing sulfonyl hydrazides, alkynyl aldehydes and allylboronate, providing allyl allenes in excellent yields and enantioselectivities. The synthetic utility of the method was demonstrated by the total synthesis of laballenic acid, a natural product isolated from the seed oil of Leonotis nepetaefolia. The enantioselective traceless Petasis reaction was also used in the synthesis of enantioenriched 1,4-dienes. The use of prochiral β-branched enals in the asymmetric Petasis allylation followed by sigmatropic rearrangement installed an sp3 stereocenter at the benzylic position, affording 1,4-dienes enantioselectively and with exclusive (E)-geometry. Asymmetric traceless Petasis crotylations were also used in the reaction with non-branched enals, affording enantioenriched products possessing the 3-methyl-1,4-diene moiety.