Rhodium-catalyzed oxidative amidation of allylic alcohols and aldehydes: effective conversion of amines and anilines into amides

Abstract

The rhodium-catalyzed oxidative amidation of allylic alcohols and aldehydes is reported.

Rhodium‐Catalyzed Asymmetric Synthesis of β‐Branched Amides

“…Similarly,d euterium incorporation at the a-position of the amide was observed (Scheme 4b), as it was in the allylic alcohol amidation, [9] supporting the reversible formation of enamine intermediate i (Scheme 2). Similarly,d euterium incorporation at the a-position of the amide was observed (Scheme 4b), as it was in the allylic alcohol amidation, [9] supporting the reversible formation of enamine intermediate i (Scheme 2).…”

“…[8] Considering the dearth of approaches for the direct asymmetric synthesis of chiral b-branched amides,w ep roposed that allylic alcohols could serve as ac hiral aldehyde precursor,w hich upon asymmetric isomerization and subsequent oxidative amidation with an amine,affords the desired product in as ingle step (Scheme 1c). [9] However,only moderate er was observed when using trisubstituted allylic alcohols as substrates. [9] However,only moderate er was observed when using trisubstituted allylic alcohols as substrates.…”

“…[9] Several allylic dialkyl amines(1a-1d)w ere screened for this tandem process (Table 1). [9] We chose to further optimize this reaction with cinnamyl diethylamine (1b), as it forms al ow molecular weight byproduct (NHEt 2 )w hich is easily removed. [9] We chose to further optimize this reaction with cinnamyl diethylamine (1b), as it forms al ow molecular weight byproduct (NHEt 2 )w hich is easily removed.…”

“…We hypothesized that acyclicd ialkyl amines could serve as precursors as they are good substrates in related Rh-catalyzed asymmetric isomerization reactions [11] and are not reactive in the oxidative amidation of allyl alcohols. [9] Several allylic dialkyl amines(1a-1d)w ere screened for this tandem process (Table 1). Under slightly modified conditions from the allylic alcohol amidation, [12] the desired morpholine amide (3a)w as formed in moderate yields from all the allylic amine precursors.O nly cinnamyl dimethylamine (1a)p rovided 9% byproduct 4a,c onsistent with dimethyl amine being an effective nucleophile in our allylic alcohol amidation.…”

“…With primary alkyl amine nucleophiles,astronger base and higher temperature were essential, which presumably aid in the conversion of the less electrophilic imine intermediate to the hemiaminal intermediate.A dditionally,a cetone proved to be the better hydrogen acceptor, consistent with our allylic alcohol amidation (Table S6). [9] With the optimized conditions in hand, the amine nucleophile scope was investigated (Table 2): cyclic amines such as piperidine (2b), indoline (2e), and 2-(piperazin-1-yl) pyrimidine (2f)and acyclicamines,including dimethyl amine (2c)and N-benzyl methyl amine (2d)all gave excellent yields of desired products.M oderate yields were obtained with aniline derivatives (2g-2j). Electron-deficient (2i)a nd sterically hindered anilines (2j)a fford slightly diminished yields.…”