Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Abstract

Catalyst and substrate studies have been performed on the rhodium-catalyzed asymmetric ring opening reaction. A working model is advanced that involves oxidative insertion with retention to form an organorhodium intermediate that then undergoes nucleophilic attack with inversion. Kinetic and competition experiments have uncovered evidence for a proton transfer step in the catalytic cycle that may activate both the allylrhodium intermediate and the nucleophile. We have also conducted experiments designed to understand which properties of the PPF-P t Bu2 ligand contribute to the high reactivities and enantioselectivities.W e have previously reported that chiral rhodium(I) catalysts induce ring opening oxa-and azabicyclic alkenes with a variety of soft nucleophiles such as alcohols, phenols, amines, anilines, malonates, and carboxylates in high yield and enantioselectivity (1-8). The products are generated by an S N 2Ј nucleophilic displacement of the bridgehead leaving group with inversion providing the 1,2-trans product as one regio-and diastereomer. The formation of the 1,2-trans products is atypical for ring opening reactions of oxabicyclic alkenes, which usually generate the syn-1,2 diastereomers via exo nucleophilic attack (1, 2). Furthermore, regio-and stereochemical results diverge from previously documented rhodium-catalyzed reactions with allylic carbonates (9-18). The observations obtained with oxabicyclic alkenes find little precedent when compared to other allylic functionalizations including those catalyzed by Pd (refs. 19 In this report we describe catalyst and substrate studies and advance a mechanistic working model that rationalizes the stereochemical outcome and other experimental observations (Scheme 1). We have also conducted experiments designed to understand the properties of the PPF-P t Bu 2 ligand that contribute to high reactivities and enantioselectivities.Experimental procedures and characterization data can be found in Supporting Text, which is published as supporting information on the PNAS web site. Ligand Studies: Variations on the Josiphos Template and Other Ligand MotifsSeveral structural elements are present on the PPF scaffold that could contribute to its successful application in these reactions (51-53). PPF has elements of central and planar chirality as well as two phosphine atoms that differ both sterically and electronically. Two methods were used to determine the influence of the ligand on the rate. In cases where a significant difference in rate was observed, percent conversion vs. time, as determined by crude 1 H NMR, was used to quantify the reactivity of the catalyst. In cases where a more precise measurement of rate was desired, kinetic runs were performed.By comparing the reactivity and enantioselectivity of ligands 3 and 4, two trends emerge (Scheme 2). First, by increasing the steric bulk ( t Bu Ͼ Cy) the enantioselectivity is increased from 88% with 3 to 96% enantiomeric excess (ee) with the bulkier t Bu 2 P ligand 4. This increase in enantioselectivity comes at ...

Mechanism, reactivity, and regioselectivity in rhodium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes: a DFT Investigation

“…The successful application of aprotic silyl ketene acetals and enol ethers, acting as the nucleophiles, also supported such a process16. Though it was found that the reaction of an alkoxide or phenoxide does not give ring-opened products18, our calculations showed that the alkoxide can poison the catalyst by coordinating to the central Rh metal (Figure S9). As expected, the forming rhodium alkoxide complexes are quite stable thermodynamically, thus the substrates are inhibited from coordinating to the rhodium.…”

“…Once M3 has been formed, the rhodium alkoxide complex could be protonated by the alcohol prenucleophile to generate cationic rhodium complex and an alkoxide or phenoxide as proposed by Lautens et al . It was thought that the proton transfer has two effects: (i) the organorhodium species is made more electrophilic as a result of the obtained positive charge, and (ii) the nucleophile is rendered to be more nucleophilic by deprotonation18. Unfortunately, all of our efforts on locating such a transition state or intermediate concerning with proton transfer were failed.…”

“…2, the commonly accepted mechanism for the ARO reaction of oxabicyclic alkenes is given by Lautens et al 18…”

Gold-catalyzed reaction of oxabicyclic alkenes with electron-deficient terminal alkynes to produce acrylate derivatives

“…Based on the previously established mechanistic model [23,77], we propose the following pathway for the formation of acrylate derivatives 3a and 3i (Scheme 4). In the presence of cationic phosphinogold(I) complex, a cationic intermediate A is formed by a regioselective opening of the oxygen bridge in substrate 1a .…”

Electrochemistry and complexation of Josiphos ligands

“…1). Josiphos ligands provide chiral catalysts that display two types of chirality, planar and central [5,6]. The two types of chirality have been found to be advantageous in a number of catalytic applications such as asymmetric allylic aminations and the asymmetric reduction of b-bdisubstituted enoates [5].…”