Paracyclophane hydrogenation

In 2004, Bolm et al. reported the use of chiral iridium complexes with chelating phosphinyl-imidazolylidene ligands in asymmetric hydrogenation of functionalized and simple alkenes with up to 89% ee [17]. These complexes were synthesized from the planar chiral [2.2]paracyclophane-based imida-zolium salts 74a-c with an imidazolylidenyl and a diphenylphosphino substituent in pseudo ortho positions of the [2.2]paracyclophane (Scheme 48). Treatment of 74a-c with t-BuOLi or t-BuOK in THF and subsequent reaction of the in situ formed carbenes with [Ir(cod)Cl]2 followed by anion exchange with NaBARF afforded complexes (Rp)-75a-c in 54-91% yield. The chela-... 

Recently, carbene-oxazoline catalysts 33 and carbene-phosphine catalysts 34 (Fig. 29.19) with a chiral paracyclophane backbone have been synthesized and used to hydrogenate a variety of alkenes, with modest selectivity [41]. 

The magnitude of the above-mentioned shifts of the ortho absorptions by various substituents (ortho shift) lies between the relatively large shifts of the hydrogen atoms cis to the substituents in vinyl compounds and the smaller ortho shifts of the usual benzene derivatives. The ortho shifts in the [2.2]paracyclophane system are thus attributed to an increased double-bond character in the deformed benzene rings, where canonical structures such as 77 could possibly contribute to stabilization of the molecule. 

Unlike other [2.2]paracyclophanes (see below), 20a exhibits remarkable chemical stability. It is inert towards bromine in carbon tetrachloride, permanganate solution, and maleic anhydride, and cannot be reduced with Pd/C or nickel at room temperature under 1 atm hydrogen pressure. 

The authors identify the new paracyclophane derivative as a catalyst lacking a hydrogen bond donor, and propose that addition is catalyzed by the Brpnsted basic imine moiety. Based on X-ray crystal data of the catalyst, it was hypothesized that... 

Pye and Rossen have developed a planar chiral bisphosphine ligand, [2.2]PHANE-PHOS, based on a paracyclophane backbone (Scheme 1.6) [69]. Moreover, the ortho-phenyl substituted NAPHOS ligand, Ph-o-NAPHOS, has been successfully applied for the rhodium-catalyzed hydrogenation of a-dehydroamino acid derivatives [70]. 

MacGillivray s group has employed rigid bifunctional molecules [42], such as 1,3-dihydroxybenzene and 1,8-naphthalenedicarboxyHc acid [42a], as linear templates to organize reactants such as fra s-l,2-bis(4-pyridyl)ethylene via hydrogen bonds for single and multiple photoinduced [2+2] cycloadditions, for the template-controlled synthesis of a l,2,3,4-(4-pyridyl)cyclobutane] [42b] and also of paracyclophanes [42d]. Very recently, [ ]ladderanes ( =2,3) have been synthesized in the solid state by UV irradiation of 2(5-methoxyresorci-nol) 2(4-pyr-poly-m-ene) (m=2,3) [42e]. 

When we first ventured into the field of [2.2]paracyclophane ligand synthesis, successful applications of such ligands were relatively rare [2]. The most prominent example was clearly the PHANEPHOS ligand developed by Rossen and Pye [3], who have found several successful applications in asymmetric hydrogenation reactions. A comprehensive survey of [2.2]paracyclophane-based ligands can be found in recent reviews [4, 5]. 

An unusual isomerization of perhydro[2.2]paracyclophane 29, an out-in hydrogen transfer process, was observed in triflic acid123 [Eq. (5.53)]. Reaction in CF3SO3D resulted in the incorporation of up to five deuteriums without specific locations. The authors suggested the backside attack of the inside hydrogen (Hj) to the bridgehead... 

A unique alternative to the traditional C2 symmetric atopisomeric motif uses a paracyclophane backbone for the placement of the phosphino groups. 4,12-Bis(phosphino)-[2.2]-paracyclophane complexes, abbreviated as PhanePhos (5), have been reported to be highly active in a few classes of asymmetric hydrogenation. The synthesis is shown in Scheme 12.51.159,160... 

A novel series of atropisomeric ligands uses a paracyclophane backbone. Rhodium and ruthe-nium-PhanePhos catalysts have performed well in the asymmetric hydrogenation of enamide esters, (3-keto esters, and especially arylketones with JST catalysts (Duloxetine). 

Bolm and coworkers very recently tested the iridium(I) complex derivatives 57a-57c in asymmetric hydrogenation [105]. These complexes contain a bidentate carbene-phosphine ligand with a chiral pseudo-ortho-[2,2]paracyclophane unit built into its backbone (Fig. 13). 

Bidentate oxazoline-imidazolylidene ligands, in which both units are linked by a chiral paracyclophane, have been studied in Bolm s group [129]. In this case, the planar chirality of the pseudo-orfho-paracyclophane is combined with the central chirality of an oxazoline (Scheme 48). Compounds 70 were tested in the asymmetric hydrogenation of olefins displaying moderate selectivity (ee s of up to 46% for dimethylitaconate in the presence of 70b). 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

A 1,4-cyclohexadienic structure (46) was proposed for the octahydroparacyclophane formed in the hydrogenation (Pt02) of paracyclophane (47), whose unusual properties provided a degree of plausibility to the claim (equation 38).Actually, four isomeric dienes, none of which has the first postulated structure, are formed. The possible structures have one trisubstituted double bond in each six-carbon cycle, as in formula (48). Dienes are more reactive than the related arenes or cyclohexenes and apparently are more tightly bound to a catalytic site. - ... 

Recently the first use of the paracyclophane backbone for the placement of two diphenylphosphano groups to give a planar chiral C2-symmetric bisphos-phane was reported [102]. The compound 159 abbreviated as [2.2]PHANEPHOS was used as a ligand in Rh-catalyzed hydrogenations. The catalytic system is exceptionally active and works highly enantioselective [ 103]. The preparation of [2.2]PHANEPHOS starts with rac-4,12-dibromo[2.2]paracyclophane (rac-157), which was metalated, transmetalated and reacted with diphenylphosphoryl chloride to give racemic bisphosphane oxide (rac-158). Resolution with diben-zoyltartaric acid and subsequent reduction of the phosphine oxides led to the enantiomerically pure ligand 159. 

---