SEGPHOS, reactions

The copper-catalyzed chiral reduction of -substituted ,/Tunsaturated lactones with PMHS and (S)-/ -Tol-BINAP in the presence of a hindered alcohol can be carried out in moderate to good yields with moderate ee values.599 The reaction is useful for both butenolides and pentenolides. Inferior results are realized with diphenylsilane as the reducing agent. Excellent results employing PMHS and the DTBM-SEGPHOS ligand are possible (Eq. 354).598... 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

The axially chiral (allenylmethyl) silanes 110 were also prepared in optically active form using chiral Pd catalysts [98]. For the asymmetric synthesis of 110, a Pd/(R)-segphos system was much better in terms of enantioselectivity than the Pd/(R)-binap catalyst. Under the optimized conditions, 110m and llOt were obtained in 79% ee (57% yield) and 87% ee (63% yield), respectively (Scheme 3.56). The enantio-merically enriched (allenylmethyl) silanes 110 served for Lewis acid-promoted SE reaction with tBuCH(OMe)2 to give conjugated dienes 111 with a newly formed chiral carbon center (Scheme 3.56). During the SE reaction, the allenic axial chirality was transferred to the carbon central chirality with up to 88% transfer efficiency. 

SEGPHOS [271, 272]. Using this complex as a precatalyst, transfer hydrogenation of 1,1-dimethylallene in the presence of diverse aldehydes mediated by isopropanol delivers products of ferf-prenylation in good to excellent yield and with excellent levels of enantioselectivity. In the absence of isopropanol, enantio-selective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts. Notably, enantioselective ferf-prenylation is achieved under mild conditions (30-50°C) in the absence of stoichiometric metallic reagents. Indeed, for reactions conducted from the alcohol oxidation level, stoichiometric byproducts are completely absent (Scheme 13). 

This chemistry was extended to a catalytic enantioselective alkenylation and phenylation of aldehydes and a-ketoesters. Using CuF-DTBM-SEGPHOS complex, products were obtained with excellent enantioselectivity from a wide range of aldehydes including aromatic and aliphatic aldehdyes, [Eq. (13.26)]. Previously catalytic enantioselective vinylation and phenylation are restricted using the corresponding zinc reagents. The active nucleophile is proposed to be an alkenyl or phenyl copper, based on NMR studies. The chiral CuF catalyst can also be applied to a catalytic enantioselective aldol reaction to ketones... 

The group of Yamamoto reported the catalytic enantioselective hetero-Diels-Alder reactions of azo compound 209 and dienes 208 (Scheme 2.54).87 In a ligand screening the use of BINAP (87) gave higher conversion and enantioselectivity than both Segphos (211) and Difluorphos (212). Interestingly, the optimal silver... 

The carbonyl-ene reaction is a source of homoallylic alcohols, although the scope is somewhat limited. Synthesis of chiral tertiary a-hydroxycarboxylic esters from glyoxyUc esters has been studied, and many metal catalysts of varying degree of effectiveness have been identified. The Ag-catalyzed reaction between enol silyl ethers and a glyoxylic ester is stericaUy controlled by the Pd-SEGPHOS complex. ... 

The higher reactivity of enol silyl ethers can he exploited in their reaction with imines. For addition to A-phosphonyl imines two types (SEGPHOS and DuPHOS) of ligands... 

Besides organocatalysts, metal complexes show catalytic activities in various types of [3+2]cycloaddition. Thus Ru complex 140 performs a role in the reaction of nitrile oxides with enals, and gold(l) benzoate complex of Cy-SEGPHOS is involved in the reaction of miinchnones with alkenes. "... 

The organopalladium species generated from coupling reaction of ArB(OH)2 with an allene is readily trapped by a properly distanced carbonyl group. Accordingly, 5,6-alkadi-enals are transformed into cw-2-(a-styryl)cyclopentanols. Adding (5)-SEGPHOS to complex the Pd salt has the desirable effect of asymmetric induction. ... 

Scheme 39 Ene reaction catalyzed by cationic SEGPHOS-Pd(II) complex...

The asymmetric Friedel-Crafts reaction of trifluoromethyl pyruvate 53 with aromatic compounds is catalyzed by cationic Pd(II) complexes with BINAP or SEGPHOS [184]. The reaction proceeded at -30 °C to afford the product 63 in 89% ee with (S)-BINAP and in 82% ee with (S)-SEGPHOS (Scheme 45). In sharp contrast to the situation of the carbonyl-ene reaction, the BINAP ligand provides higher enantioselectivity than the SEGPHOS ligand. 

Related to Gutnov s procedure is the highly enantioselective construction of 4-arylp5uidones by Tanaka et al. (090L1805). The reaction is catalyzed by a cationic palladium(lD/(S)-xyl-Segphos complex 586 (Ar = 3,5-Me2-C6H3) and 2-p) idones 587 are obtained in up to 96% 5deld and up to 97% ee. 

Ene reaction of 26 with ethyl trifluoropyruvate (29) proceeded with high enan-tioselectivity using the dicationic Pd catalyst prepared by the reaction of SEGPHOS (XIV-3)-PdCl2 with AgSbFg to give 30 with 96% ee quantitatively [8]. 

MK-1597. A similar procedure was used for the hydrogenation of a close analog for a related renin inhibitor (ee 99%, ton 100, tof 20 h ) [99] (Scheme 43). A catalyst prepared in situ from [Ru(cymene)Cl2]2 and-dm-segphos in presence of NH4OAC was used by Takasago [100] for the reductive amination of p-keto esters with very high enantioselectivities. The reaction shown in Scheme 44 was carried out on the 66-kg scale. 

All of the examples shown (Scheme 6-17), except for aryl imines, have S/L ratios of >1000 1 (imines <100 1). For selected educts such as acetophenone, the TON is >100,000 using either CuH complexed by ligand 169 or 170, while for isophorone, it is >275,000 1 with (DTBM-SEGPHOS)CuH (procedure below). 1,2-Additions are temperature sensitive in that ee s improve as reactions are cooled toward -78 The variation in ee s between temperatures can easily be >10%,... 

To a 25 mL, round-bottom filter flask, flame dried and purged with argon, was added Cu/C (134.4 mg, 0.046 mmol), NaOPh (24 mg, 0.2 mmol), and DTBM-SEGPHOS (1.2 mg, 0.001 mmol). Toluene (10 mL) was added and allowed to stir for 90 min. PMHS (1.2 mL, 20 mmol H ) was added dropwise and stirred for 30 min. Isophorone (3 mL, 10 mmol) was added neat, and the reaction was placed in a sonication bath until complete as judged by TLC analysis (3 h 4 1 hexanes/EtOAc). The reaction vessel was inverted and filtered in vacuo into a 100-mL, round-bottom flask. The filter cake was washed with toluene (2 x 10 mL) and filtered in vacuo. The 100-mL, round-bottom flask was quenched with aqueous NaOH (50 mL, 3 M) and allowed to stir at RT for 3 h. The residue was purifieii by flash chromatography (4 1 hexanes/EtOAc) to afford the title product (1.195 g, 85% yield) as a clear oil. Analysis of the residue by GC showed 98.5% ee [Chiraldex-BDM column with 75 °C isotherm, R,= 41.47 (minor) and 44.94 (major)]. 

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