Chain Walking of Allylrhodium Species Towards Esters During Rhodium‐Catalyzed Nucleophilic Allylations of Imines

Abstract Allylrhodium species derived from δ‐trifluoroboryl β,γ‐unsaturated esters undergo chain walking towards the ester moiety. The resulting allylrhodium species react with imines to give products containing two new stereocenters and a Z‐alkene. By using a chiral diene ligand, products can be obtained with high enantioselectivities, where a pronounced matched/mismatched effect with the chirality of the allyltrifluoroborate is evident.

The migration of metal centers along carbon chains occurs in several important reactions. [1][2][3][4][5][6][7] Many of these migrations take place by b-hydride elimination and hydrometalation sequences,i nw hich the direction of travel is controlled by thermodynamics,aligand, or an earby functional group. With few exceptions, [4b-f] these migrations involve simple alkylmetal species.The ability to chain walk ametal together with as econd functional group has significant synthetic opportunities,b ut this mode of reactivity remains largely underdeveloped. Herein, we describe,t oo ur knowledge,t he first examples of allylrhodium chain walking,and its application in the preparation of enantioenriched products.
Ther eaction of 1b with allyltrifluoroborate 2h,i nw hich boron is bonded to aprimary rather than asecondary carbon, gave not only 3s,but also asignificant quantity of product 7 in 80:20 d.r., derived from allylation without chain walking [Eq. (1)]. [14] Products 3s and 7 could not be completely separated by column chromatography,a nd their yields were determined by 1 HNMR analysis using an internal standard.
Interestingly,t he reaction of Z-allyltrifluoroborate 8 [9] with aldimine 1b gave 3b in 70 %y ield (Scheme 2, top), which is the same product obtained from the corresponding E-isomer 2a ( Table 1, entry 2). Furthermore,despite possessing asubstitution pattern different to all allyltrifluoroborates employed until this point, allyltrifluoroborate 9 reacted in the same manner to give 3t (Scheme 2, bottom). [10] These results suggest that regardless of the geometrical or positional isomerism of the allyltrifluoroborate within the b to d carbons,t he reactions proceed through common types of allylrhodium intermediates.H owever,h omoallylic boron reagents were unreactive. [13,15] Because these reactions provide chiral products from chiral substrates,w ei nvestigated whether enantioenriched allyltrifluoroborates would give enantioenriched products. However,t he reactions of (R)-2a (94 % ee) [9] with aldimine 1b and ketimine 1f gave (S,S)-3b and (S,S)-3f,r espectively, with low-to-moderate enantiomeric excesses (Scheme 3). Although chain walking of alkylmetal species can proceed with high stereospecificity, [7c] poor absolute stereochemical transfer is observed in the reactions described herein.
Next, chiral rhodium complexes were investigated for their ability to provide enantioenriched products from racemic allyltrifluoroborates (Scheme 4). [8b] Although several chiral dienes [16] gave poor conversions [13] in the reaction of aldimine 1b with 2a,diene L1 [17] gave (S,S)-3b in 72 %y ield and 98 % ee.S everal other products (S,S)-3k,( S,S)-3m,a nd (S,S)-3p were also prepared in the same manner. However, the yields of some of these reactions were low,and the scope is more limited than when using [{Rh(cod)Cl} 2 ]. Fore xample, enantioselective additions to ketimines were unsuccessful. Interestingly,apronounced matched/mismatched effect was observed with enantioenriched allyltrifluoroborates.T he reaction of 1b with (R)-2a (94 % ee)u sing chiral diene L1 gave (S,S)-3b with results identical to the reaction using racemic 2a (Scheme 5, top;c ompare with Scheme 4). However,t he corresponding reaction with (S)-2a (94 % ee)g ave ac omplex mixture;a lthough 3b was detected in small but unquantifiable amounts by 1 HNMR analysis,itc ould not be isolated. Currently,i ti su nclear which steps of the proposed mechanism (see below) are rendered inefficient by the stereochemical mismatch of the ligand and the allyltrifluoroborate.
Ap roposed mechanism, using imine 1a and allyltrifluoroborate 2aas representative substrates,isshown in Scheme 6. Ther eaction of 2a with iPrOH can reversibly generate am ixed alkoxide/fluoride boron ate complex 11,w hich transmetalates with rhodium complex 10 [18,19] to give interconverting allylrhodium species 12 and 13. b-Hydride elimination of 13 then gives ar hodium hydride species bound to ethyl sorbate (as in 14). [20,21] Hydrorhodation of the alkene distal to the ester then provides interconverting allylrhodium species 5 and 6.Apossible driving force for this chain walking migration is the formation of amore stable,more conjugated
In summary,w eh ave reported the chain walking of allylrhodium species derived from d-trifluoroboryl b,g-unsaturated esters during the rhodium-catalyzed nucleophilic allylation of imines,w hich gives products with two new stereocenters and a Z-alkene.E nantioselective catalysis is possible using achiral diene ligand, where astrong matched/ mismatched effect was observed. Further exploration of this new mode of reactivity is underway in our laboratories.