Asymmetric Total Synthesis of (+)-Epiibogamine Enabled by Three-Component Domino Michael/Michael/Mannich Annulation of N-Sulfinyl Metallosilylenamines.

The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate. The novel N-sulfinyl silylenamine reagent enabled the key step, with three-component domino Michael/Michael/Mannich annulation providing the 1-amino-2,4-diester scaffold with four new chiral centers, and access to the isoquinuclidine in high yield (84%) and diastereoselectivity (>95:5 dr).

Diastereoselective Hydroxylation of N-tert-Butanesulfinyl Imines with 2-(Phenylsulfonyl)-3-phenyloxaziridine (Davis Oxaziridine).

The diastereoselective α-hydroxylation of N-tert-butanesulfinyl metallodienenamine and metalloenamines with Davis oxaziridine affords α-hydroxy N-sulfinyl imines with 50-88% yield and up to 98:2 diastereomeric ratio. Dramatic changes in diastereoselectivity and stereoselectivity were observed by choice of metal bases. The mechanistic understanding for the switch in diastereoselectivity was assisted by DFT computational modeling, which suggests the facial approach is governed by aza-enolate geometry. A one-pot protocol for the asymmetric synthesis of 1,2-amino alcohols is described.

Oxidative addition of activated aryl-carboxylates to Pd(0): divergent reactivity dependant on temperature and structure.

With the exception of activated sulfonate esters, oxidative addition of Ar-O bonds to Pd(0) complexes is extremely rare. This has led to a general perception that Pd-catalyzed cross-coupling is not feasible with O-based electrophiles such as aryl esters. We report that pyrone and coumarin esters do undergo oxidative addition to Pd(PCy3)2, with Pd insertion into either the acyl-O or Ar-O bond. Addition of the acyl-O bond to Pd(0) is kinetically favoured and reversible, while addition of the Ar-O bond is thermodynamically favoured. Using a larger and more electron-rich pivalate derivative disfavours acyl-O cleavage, enabling selective oxidative addition of the Ar-O bond and corresponding catalytic cross-coupling.

Imidazolyl-phenyl (IMP) anions: a modular structure for tuning solubility and coordinating ability.

The effect of counteranion upon a cation's solution-phase reactivity depends on a subtle interplay of weak interactions. Although these effects are widely appreciated in synthesis and catalysis, probing and controlling anion-cation interactions remains a significant challenge. Here we report the synthesis, characterisation and reactivity of the IMP anions, a family of anions with a coordinating ability that can be tuned for a given application. The anions are robust, compatible with both strongly basic and acidic media, suitable for isolation of unstable organometallic species, and effective as counteranions for homogeneous catalysis. IMP anions are prepared in two steps: deprotonation of substituted 2-phenylimidazoles with NaH, followed by addition of 2 equiv. B(C6F5)3. The anions prepared feature a range of functionality, including nitro, ester, amide, amine and alcohol groups. Based on the spectroscopic properties of [Pd(IPr)(C(O)C9H6N)] [IMP-R], the coordinating ability of [IMP-R]- ranges between BF4- and BArF4-, depending on the polarity of the R group. Gold complexes of type [L-Au-L'][IMP-R] have been isolated and characterised, resulting in the first X-ray structure of a (η2-diphenylacetylene)Au complex. [(tBuXPhos)Au(MeCN)][IMP-R] catalyses [2 + 2] cyclisation of alkenes and alkynes, as well as the hydroalkoxylation of alkynes. Unlike SbF6- and BArF4-, the [IMP-H]- and [IMP-CF3]- salts are sufficiently soluble to efficiently promote cyclisations in toluene with [(tBuXPhos)Au(MeCN)]+.