A new approach toward ferrocenyl phosphapalladacycle construction from achiral enones via asymmetric hydrophosphination and subsequent diastereoselective C−H activation is described. Its catalytic efficacy toward C−C bond formation is subsequently illustrated. F errocenyl phosphines incorporating central and planar chirality elements have a proven track record as powerful auxiliaries in asymmetric synthesis. 1 As a result, extensive efforts have been invested in their challenging synthesis. 2 These pursuits focused on the development of ferrocenyl diphosphine and phosphapalladacyclic systems, which contain both the aforementioned stereogenic components on the same molecule. The synthesis of ferrocenyl phosphapalladacycles generally comprises two steps, i.e, (i) the formation of a C-chiral monophosphine and (ii) subsequent palladation via C−H/C− Br activation. There are a couple of traditional approaches by which the former may be achieved, either through enantioselective 3 /diastereoselective 4 lithiation controlled by pre-existing chiral element(s) or secondary phosphine substitution of an enantiopure Ugi amine derivative. 5 Both these methods although highly selective and synthetically relevant are, however, limited by the necessity of employing an enantiopure substrate. The desired ferrocenyl phosphapalladacycle may then be secured by either diastereotopic C−H activation 6 or oxidative addition of palladium(0). 7 A hitherto unexplored route for the enantioselective formation of monoferrocenyl phosphines is the palladiumcatalyzed asymmetric hydrophosphination (AHP) reaction. The emergence of AHP of activated alkenes affording high yields, short reaction times, and excellent selectivities offers an atom-economical yet efficient approach to achieve this goal. 8 However, ferrocenyl-appended substrates have been conspicuously absent from this library. Furthermore, the use of these chiral monophosphine adducts toward the preparation of viable catalysts has rarely been explored. Herein, we report the AHPbased enantioselective construction of a series of C-chiral tertiary ferrocenyl phosphines and the subsequent diastereoselective cyclopalladation of one of the congeners. We began our investigation by screening an array of conditions for the asymmetric addition of diphenylphosphine to 1a catalyzed by (S)-3 (Table 1).During the optimization process, it was evident that while the AHP proceeded smoothly in DCM and MeOH, poor conversions were obtained with THF, acetone, and acetonitrile. Results show a pronounced difference between the performances of the two catalysts (entry 3 vs 4). While the N−C palladacycle (S)-3 catalyzed the reaction within 2 h at RT, its P−C analogue (S)-4 failed to deliver full conversion even after Table 1. Palladacycle-Catalyzed AHP of 1a a entry solvent t (h) yield b (%) ee c (%)

Ferrocenyl phosphines targeting the digestive vacuole function of the malaria parasite, Plasmodium falciparum.

Hitherto inaccessible multisubstituted thiochroman derivatives were constructed via the one-pot reaction of thiophenols with allylic alcohols catalyzed by 0.2 equiv triflic acid under metal-free conditions. A variety of thiochroman derivatives can be obtained by this straightforward protocol that allows the introduction of up to four substituents at various locations on the thiochroman skeleton. Relative conformations of all isolated products were confirmed by NOESY NMR studies, and a stepwise mechanism, proceeding via an allylic substitution-intramolecular cyclization protocol, is proposed on the basis of NMR experiments.

Asymmetric addition of diarylphosphines to oxa- and azabicyclic alkenes proceeded in the presence of a chiral phosphapalladacycle catalyst and a mild acid at room temperature to give exclusively the enantioenriched addition products in excellent yields and good selectivities. Three new chiral carbon centers were generated stereoselectively by the catalytic hydrophosphination reaction.

The kinetic resolution of racemic 5-substituted alkylcyclohexenones via 1, 4-conjugate addition with a variety of arylboronic acids was achieved by utilizing a ferrocenyl phosphapalladacycle catalyst. The addition reaction proceeded smoothly to afford trans-3-alkyl-5-arylcyclohexanones in good yields and selectivities. † Electronic supplementary information (ESI) available. See