Phosphoramidite ligand

Phi = NTs ([N-(p-toluenesulfonyl)iminio]phe-nyliodinane) 79 phomactin A 307 (+)-phonomactin 277 ( )-phoracantholide 299 phosphazene base 3 f. phosphazine base 31 phospholene epoxide 243 phosphoramidite 261 phosphoramidite ligand 247 piperidinephosphonate 103 pipermethystine 302 P K 177... 

Feringa and co-workers applied chiral phosphoramidite ligand (S,R,R)-67 in the conjugate addition of dimethylzinc to acyclic unsaturated malonates 68 and obtained up to 98% ee (Scheme 22).71... 

The enantioselective conjugate addition of dialkylzinc to nitroalkenes using other phosphoramidite,79,79a 83a sulfonamide,84 and binaphthol-based thioether ligands65 has also been studied in the past few years. Particularly noteworthy are the efficient chiral monodentate phosphoramidite ligands (S,R,R)-29 and (A,A)-55 developed by Feringa et al. and Alexakis et al., respectively, for this reaction. (S,R,R)-29 provided excellent enantioselectivities (up to 98% ee) for acyclic nitroalkenes (Scheme 25).80 It also worked well for other nitroolefin substrates such as 3-nitrocoumarin 7068 and methyl 3-nitropropenoate 7185. 

Alexakis et al. showed that under optimized experimental conditions, the enantioselectivity of the Cu-catalyzed conjugate addition of dialkylzinc to cyclic nitroolefin was improved to 95% with both (A,A)-55 and (R,S,S)-29.79,79a Biphenol-based phosphoramidite ligand (S,S)-55 also provided acyclic nitroalkenes adducts with 95-96% ee.42... 

Platinum catalysts are also effective for the silaboration of 1,3-dienes.234 Although almost no stereoselectivitiy is observed in the silaboration of acyclic 1,3-dienes, 1,3-cyclohexadiene undergoes the stereoselective silaboration in fair yields (Equation (87)). Enantioselective silaboration of 1,3-cyclohexadiene has been achieved with 70% ee by using a platinum catalyst bearing a binol-based optically active phosphoramidite ligand.235... 

Table 4 Hydroboration of norbornene using phosphoramidite ligands 35-38...

The use of phosphite-phosphoramidite ligands 168 a and b provided up to 98% ee in the hydrogenation of methyl (Z)-N-2-acelylarrii noci rinamale, but the activities were rather low when compared to 167 or to the corresponding diphosphine ligand [126]. 

The majority of the reported phosphoramidite ligands consist of BINOL and a diversity of readily available amines. Excellent enantioselectivities in the hydrogenation of a- and /fdehydroamirio acids, itaconates and enamides [63, 64] have been reported. In a recent full report, the group of Minnaard, De Vries and Fer-inga noted that especially the BINOL-derived ligands containing a piperidine or... 

Phosphoramidite ligands based on TADDOL (36) and on D-mannitol (37) [74] have also been used (Scheme 28.11). However, the enantioselectivities reported for the hydrogenation of a-dehydroamino acids and itaconates were generally lower compared to the ligands based on BINOL. A different strategy is the use of ligands 38a-g based on the achiral diol catechol, and chiral amines [75]. 

The X-ray structure of the Cut complex 21 of phosphoramidite 14 provides additional insight into a possible mechanism for stereocontrol (Fig. 7.3). The formation of the L2CuEt-enone complex involves substitution of the iodide in 21 for the alkyl moiety and of one of the ligands for the -coordinated enone. Coordination of RZnX results in the bimetallic intermediate 19 (Fig. 7.3). The absolute configuration of the two phosphoramidite ligands and the pseudo-C2-symmetric arrangement dictate the formation of (S)-3-ethyl-cyclohexanone. 

Scheme 7.13. TADDOL-based phosphoramidite ligands in the catalytic 1,4-addition.

The moderate ees obtained with the copper arenethiolate ligands discussed above prompted a search for new chiral ligands for use in asymmetric allylic substitution reactions. The binaphthol-derived phosphoramidite ligand 32, used successfully by Feringa et al. in copper-catalyzed 1,4-addition reactions [37], was accordingly tested in the reaction between 21 and n-BuMgl. 

Fig. 8.5. Binaphthol-derived phosphoramidite ligands developed by Feringa et al.

A wide range of carbon, nitrogen, and oxygen nucleophiles react with allylic esters in the presence of iridium catalysts to form branched allylic substitution products. The bulk of the recent literature on iridium-catalyzed allylic substitution has focused on catalysts derived from [Ir(COD)Cl]2 and phosphoramidite ligands. These complexes catalyze the formation of enantiomerically enriched allylic amines, allylic ethers, and (3-branched y-8 unsaturated carbonyl compounds. The latest generation and most commonly used of these catalysts (Scheme 1) consists of a cyclometalated iridium-phosphoramidite core chelated by 1,5-cyclooctadiene. A fifth coordination site is occupied in catalyst precursors by an additional -phosphoramidite or ethylene. The phosphoramidite that is used to generate the metalacyclic core typically contains one BlNOLate and one bis-arylethylamino group on phosphorus. 

In this and subsequent studies [41 14], Takeuchi and coworkers described the scope and selectivity of catalysts derived from [fr(COD)Cl]2 and achiral phosphorus ligands. Many of the trends that they uncovered have also been observed with more recently developed catalyst systems derived from chiral phosphoramidite ligands (Table 1). 

The phosphoramidite ligands that are the focus of the remainder of this chapter have prompted the investigation of ligands containing related structures. Iridium complexes of aspartic acid-derived P-chirogenic diaminophosphine oxides (DlAPHOXs) catalyze the amination [62] and alkylation [63] of aUyhc carbonates (Scheme 6). With BSA as base and catalytic amounts of NaPFs as additive, branched amination and alkylation products were obtained from cinnamyl carbonates in excellent yields and enantioselectivities. However, the yields and enantios-electivities were lower for the reactions of alkyl-substituted aUyhc carbonates. Added LiOAc increased the enantioselectivities of aUyhc alkylation products. 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

Advances in Mechanistic Understanding and Catalyst Design Cyclometalation and Modification of the Phosphoramidite Ligand... 

Although the combination of [Ir(COD)Cl]2 and LI was shown to catalyze the alkylation, amination, and etherification of allyiic esters to form the branched substitution product in high yield and enantioselectivity, the identity of the active catalyst in these reactions had not been identified. The combination of [Ir(COD) Cl]2 and LI forms the square-planar [Ir(COD)(Cl)Ll] (4) (Scheme 11) [45]. However, this complex does not react with allyiic carbonates to form an appreciable amount of an aUyl complex, and the absence of this reactivity suggested that the mechanism or identity of the active catalyst was more complex than that from simple addition of the allyiic ester to the square-planar complex containing a k -phosphoramidite ligand. 

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