Enantioselective, Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes

Abstract

The gold-catalyzed enantioselective hydroazidation and hydroamination reactions of allenes are presented herein. ADC gold(I) catalysts derived from BINAM were critical for achieving high levels of enantioselectivity in both transformations. The sense of enantioinduction is reversed for the two different nucleophiles, allowing access to both enantiomers of the corresponding allylic amines using the same catalyst enantiomer. Graphical AbstractChiral allylic azides and amines may be obtained by enantioselective hydroazidation and hydroamination of allenes catalyzed by acyclic diaminocarbene gold(I) catalysts derived from BINAM. The sense of enantioinduction is reversed for the two different nucleophiles, allowing easy access to both enantiomers with a single catalyst enantiomer. Keywordshydroazidation; hydroamination; enantioselective; gold catalysis; acyclic diaminocarbene Allylic amines are an important functional motif in synthetic organic chemistry and they have been utilized in the synthesis of numerous biologically active compounds. [1] Closely related allylic azides are valuable precursors for allylic amines, as well as for amino acids [2] Correspondence to: F. Dean Toste, fdtoste@berkeley.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript and amine-containing natural products. [3] Allylic azides have typically been prepared via substitution reactions from the corresponding allylic halides, (homo)allylic alcohols, and their derivatives. [4] More recently, Pd-catalyzed C-H activation, [5] and Au-catalyzed hydroazidation of allenes [6] have been employed.While reports of the synthesis of allylic azides are numerous, methods for asymmetric azidation are few. [7] Fewer still are enantioselective hydroazidation reactions, which have only been reported in a formal sense via conjugate addition to activated double bonds (Scheme 1). [8][9][10] In light of recent examples of transition-metal catalysed asymmetric additions of nitrogen nucleophiles to allenes [11] and the growing utility of organic azides, we sought to develop a gold(I)-catalyzed enantioselective hydroazidation of allenes. Cognizant of potential regioselectivity issues from the Winstein rearrangement [12] of the product allylic azides, we initiated our studies using aryl allene 3a. [13] Initial studies revealed that the use of ethereal solvents was critical to obtaining reproducible data. [14] With the choice of solvent established, the enantioinduction afforded by a number of chiral gold(I) catalysts was evaluated under conditions similar to those previously reported, with trifluoroacetic acid (TFA) and trimethylsilyl azide (TMSN 3 ) used for in situ generation of hydrazoic acid (Table 2). [6] Traditional chiral phosphine gold(I) catalysts failed to afford high levels of enantioinduction (entries 1,2) as did a previously reported [15] phosphoramidite catalyst (entry 3). Chiral NHC gold(I) catalysts [16] (entries 4-6) also were found to be unsatisfactory. However, the use of a BINAM-derived ADC gold...

Asymmetric gold catalysis enabled by specially designed ligands

“…The trend of utilizing ADCs for enantioselective gold catalysis continued, and another interesting series of H 8 -BINAMderived acyclic diaminocarbenes was revealed by Toste and coworkers in 2016. 162 The modular and convergent synthesis of these ADCs from the corresponding amines and gold isocyanides makes them more appealing chiral ligands. The authors demonstrated the applications of newly developed ligands for gold(I)-catalysed enantioselective hydroazidation and hydroamination reactions of allenes (39a) (Scheme 39).…”

Transition-metal acyclic carbene complexes: building blocks for luminescent, stimuli-responsive, bioactive materials and catalysts

“…17) have shown good catalytic activity for addition reactions to alkenes and alkynes. Selected examples include hydration of ethynylbenzenes, 31 addition of enynes with indoles, 94 hydroazidation and hydroamination of allenes, 98 and hydrosilylation of alkynes. [99][100][101] Most of the addition reactions catalyzed by Au(I) acyclic carbene complexes can be performed at room temperature under mild reaction conditions, while the Pt(II) acyclic carbene complexes work at elevated temperatures of 80-100 1C.…”

“…Similarly, the enantiomeric selectivity of the asymmetric catalytic addition reactions can be enhanced by the introduction of chiral substituents on the acyclic carbene ligands (Table S3, ESI †). 98 Acyclic carbene complexes (Fig. 18) have also been reported to catalyze addition reactions of aldehydes and ketones (Scheme 6).…”

“…Similarly, the enantiomeric selectivity of the asymmetric catalytic addition reactions can be enhanced by the introduction of chiral substituents on the acyclic carbene ligands (Table S3, ESI†). 98…”

Metal-Catalyzed Intermolecular Hydrofunctionalization of Allenes: Easy Access to Allylic Structures via the Selective Formation of C–N, C–C, and C–O Bonds

“…82 N-carbamates were also successfully tested by Toste with an enantioselective gold-based catalytic system hydroamination of 1,3-disbustituted allenes. 50 Noteworthy, the team of Breit reported in 2017 the rhodium catalyzed enantioselective hydroamidation of terminal allenes with quinazolones (Scheme 27). 83 The addition of the nucleophile was observed on the-carbon of the allene in the presence of a rhodium/diphosphine system combined with (R)-camphorsulfonic acid.…”