Arylative Intramolecular Allylation of Ketones with 1,3‐Enynes Enabled by Catalytic Alkenyl‐to‐Allyl 1,4‐Rhodium(I) Migration

Abstract Alkenyl‐to‐allyl 1,4‐rhodium(I) migration enables the generation of nucleophilic allylrhodium(I) species by remote C−H activation. This new mode of reactivity was employed in the diastereoselective reaction of arylboron reagents with substrates containing a 1,3‐enyne tethered to a ketone, to give products containing three contiguous stereocenters. The products can be obtained in high enantioselectivities using a chiral sulfur‐alkene ligand.

could then undergo a1 , 4-rhodium(I) shift to the cis-allylic substituent to give the allylrhodium(I) species B,which could be trapped by an electrophile.This approach was expected to be challenging,given that there is only very limited precedent for rhodium(I) to migrate to C(sp 3 )c enters. [12d,14k,m] Nevertheless,t he generation of electrophilic allylrhodium(III) species by as imilar strategy in our rhodium(III)-catalyzed oxidative annulations of 1,3-enynes provided some encouragement. [10] Herein, we describe the implementation of this strategy in arylative intramolecular allylations of ketones to give stereochemically complex fused bicycles with high diastereoselectivities.P reliminary results of enantioselective reactions are also provided.
In the proposed catalytic cycle (Scheme 2), transmetalation of the arylboronate with the rhodium methoxide 4 provides the arylrhodium species 5,w hich undergoes migratory insertion with the alkyne of 1a to give alkenylrhodium species 6.1 ,4-Rhodium migration gives the allylrhodium species (Z)-7,w hich cyclizes onto ak etone to provide the rhodium alkoxide 8.M ethanolysis of 8 liberates the product 2aa or 2ab and regenerates 4.
Up until this point, all of the arylboronates evaluated possess substitution patterns that disfavor 1,4-rhodium(I) migration of intermediates such as 6 onto the aryl group.T o assess whether alkenyl-to-allyl 1,4-rhodium(I) migration would still be favored when as terically more accessible site is available, 1a was reacted with phenylboronic acid (Scheme 4). Ther eaction in TBME/tBuCN (8:1) in the presence of t-amyl alcohol (1.5 equiv) gave a9 5:5m ixture of inseparable products, 15 and 2ja.T he product 15 results from 1,4-rhodium(I) migration onto the phenyl group followed by intramolecular ketone arylation, [15] whereas 2ja is the arylative allylation product. When the solvent was changed to 2-MeTHF,t he allylation product 2jb was formed preferentially (36:64 ratio of 15/2jb)i n8 9:11 d.r., and was isolated as as ingle diastereomer in 45 %y ield. The reasons for this switch in chemoselectivity are not currently known.
Consistent with models proposed in prior rhodiumcatalyzed nucleophilic allylations, [4a, 12b-e] we suggest that allylation occurs through cyclic six-membered transition states (Scheme 5). In the absence of an itrile in the reaction medium (Table 1, entry 1), we assume that (Z)-7,f ormed from 1,4-rhodium(I) migration of 6,c yclizes through ac hairlike arrangement (TS1)togive 2aa (Scheme 5). Theboatlike structure TS2 should be disfavored. However, when acoordinating nitrile is present (Table 1, entries 2a nd 3), the rate of cyclization could be decreased, allowing isomerization of (Z)-7 into (E)-7. [22] Thereafter,weassume that cyclization of (E)-7 occurs through the chairlike conformation TS5 to give 2ab (Scheme 5). Thealternative conformation TS3 is likely to be disfavored because of 1,3-diaxial interactions and allylic 1,3strain. Theb oatlike structure TS4 is also likely to be unfavorable.H owever,w ed on ot exclude the possibility that when anitrile is present, 2aa is formed by cyclization of (E)-7 through an open transition state because of preferential coordination of rhodium to the nitrile rather than the ketone.
Similar chairlike transition states can be used to explain the outcomes of the reactions 12 a and 12 b [Eqs. (2) and (3)], and the diastereomeric ratios observed may be aconsequence of their more flexible nature (see the Supporting Information).