Transfer of Chirality in the Rhodium‐Catalyzed Intramolecular [5+2] Cycloaddition of 3‐Acyloxy‐1,4‐enynes (ACEs) and Alkynes: Synthesis of Enantioenriched Bicyclo[5.3.0]decatrienes

Abstract

Chiral Bicyclic Bicyclo[5.3.0]decatrienes were prepared enantioselectively for the first time from readily available chiral 3-acyloxy-1,4-enynes (ACEs). The chirality of the allylic/propargylic esters in ACEs could be transferred with high efficiency to the bicyclic products in most cases. The experimentally observed overall inversion of stereochemistry confirmed the prediction from previous computational studies.

3-Acyloxy-1,4-enyne: A new five-carbon synthon for rhodium-catalyzed [5 + 2] cycloadditions

“…A match-mismatched scenario is expected for substrates 25a and 25b with two stereogenic centers (Scheme 6) [37]. Indeed, the cycloaddition for 25a was completed in 18h with 84% yield of the desired product without noticeable erosion of the diastereomeric ratio (dr).…”

“…The Rh-catalyzed intramolecular (5+2) cycloaddition of ACE and alkyne is also enantiospecific (Scheme 5) [37]. Based on the absolute stereochemistry of the propargylic ester starting material and the bicyclic product, which was determined by X-ray diffraction, the Rh-catalyst should approach the ACE from the face opposite to the acyloxy group.…”

Rhodium-Catalyzed Stereoselective Intramolecular [5 + 2] Cycloaddition of 3-Acyloxy 1,4-Enyne and Alkene

“…12 We recently found that 3-acyloxy-1,4-enyne (ACE) could also serve as a 5-carbon component for Rh-catalyzed [5+2] cycloaddition with alkynes for the synthesis of cycloheptatrienes (Scheme 1). 13 A 1,2-acyloxy migration was accompanied with this [5+2] cycloaddition. 14 We herein report the first Rh-catalyzed highly stereoselective intramolecular [5+2] cycloaddition of ACEs and alkene for the synthesis of bi-cyclo[5.3.0]decane carbon skeletons, which are present in numerous bioactive sesquiterpenes and diterpenes (Scheme 1).…”

“…This was demonstrated by the successful Rh-catalyzed [5+2] cycloadditions of this type of electron-deficient ACEs and alkynes. 13 We were pleased to find that ACEs in substrates 1i , 1j , and 1k also underwent [5+2] cycloadditions with the tethered alkenes (entries 8–10). A small amount of isomeric diene products was observed in these cases.…”

“…10b,19 Inspired by Toste’s work on Au-catalyzed Rautenstrauch rearrangement 20 of enantio-enriched ACEs to cyclopentenones 21 through a center-to-helix-to-center chirality transfer mechanism, 22 we demonstrated that it was also possible to transfer the chirality from ACEs to bicyclic products in Rh-catalyzed intramolecular [5+2] cycloaddition of ACEs and alkynes. 13c If a similar process can be realized for the cycloaddition between ACE and alkene, we will then be able to access highly valuable enantio-enriched 5–7 bicyclic products with multiple stereogenic centers from readily available starting materials. Substrates 1b , 1m , and 1n were easily prepared with high optical purity from the corresponding propargylic alcohols (Scheme 2).…”