Perfluorinated Taddol phosphoramidite as an L,Z-ligand on Rh(i) and Co(−i): evidence for bidentate coordination via metal–C6F5 interaction

Abstract

Perfluorinated Taddol-based phosphoramidite, CKphos, is a highly selective ligand for formation of the vinylogous amide cycloadduct in the Rh(I) catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and alkynes. CKphos overrides substrate bias of product selectivity in the cycloaddition, providing indolizinones in excellent product and enantioselectivities. Excellent selectivities are attributed to a shortened Rh-P bond and coordination of one C6F5 to rhodium via a Z-type interaction, making the phosphoramidite a bidentate L,Z-ligand on rhodium. Evidence for the shortened Rh-P and C6F5 coordination is provided by X-ray, NMR and DFT computation analyses. Additionally, an anionic cobalt complex with CKphos was synthesized and two Co-C6F5 interactions are seen. Rh(C2H4)Cl•CKphos catalyst in the [2+2+2] cycloaddition of alkenyl isocyanates and alkynes represents a rare example of metal-C6F5 Z-type interaction affecting selectivity in transition metal catalysis.

A Catalytic Asymmetric Synthesis of Polysubstituted Piperidines Using a Rhodium(I)‐Catalyzed [2+2+2] Cycloaddition Employing a Cleavable Tether

“…The recently developed electron withdrawing phosphoramidite, CKphos , proved to be the best ligand (Table 1, entry 5). [18] Using CKphos , vinylogous amide was obtained in 77% yield and 94% ee . As expected with CKphos , product selectivity favored 3 over 4 by >19:1.…”

Enantioselective Synthesis of the Tricyclic Core of FR901483 Featuring a Rhodium-Catalyzed [2+2+2] Cycloaddition

“…7–9 Extensive phosphoramidite ligand (L*) optimizations has led to a broader scope of heterocycles since one can control the selective formation of bicyclic lactams ( 4 ) or vinylogous amides ( 5 ), the latter arising from a CO migration. With terminal alkynes ( I, II ) 7 and unsymmetrical internal alkynes ( III, IV ), 8a single regioisomeric products are obtained in good yields and excellent enantioselectivities.…”

“…To overcome this preference, we have developed phosphoramidite ligands L1 (GuiPhos) and L2 as a solution to the selective formation of vinylogous amide adducts with alkyl acetylenes. 7d,e Unfortunately, to date these two ligands have proven inefficient for the synthesis of indolizidines with aza -quaternary stereocenters, delivering the vinylogous amide adducts with moderate product- and enantioselectivities. However, the impact of substitution on the tether was unknown and we speculated that it might play to our advantage.…”

“…As previously observed, GuiPhos ( L1 ) leads to higher enantioselectivities in comparison to L2 . 7d,e However, the only substrate that affords a cycloadduct with a useful enantioselectivity (94% ee) is isocyanate 9b with a gem -dimethyl substituent at C2 (entry 3). Alkenyl isocyanates 9c–e , bearing C2 substituents that could potentially lead to the needed carbonyl/alcohol for the synthesis of FR901483, generate vinylogous amide products with moderate enantioselectivities (54–65% ee).…”

“…The real breakthrough came with the advent of CKPhos ( L3 ), which improves upon L1 and L2 in both product- and enantioselectivity. 7f This electron-deficient TADDOL phosphoramidite ligand greatly overcomes the inherent preference of alkyl alkynes to form lactam indolizinones and mainly provides vinylogous amide products 14 with excellent control of product- (up to 1:14), regio- (single isomer) and enantioselectivities (up to 99% ee). In this series of dienyl isocyanates, 12b (entry 6) affords the best combination of results (product selectivity, yield and enantioselectivity).…”