Phosphoramidite examples

Another example of the palladium-catalyzed asymmetric hydrosilylation of simple terminal alkene, 1-hexene, was reported recently where rfl-phosphoramidite 21d gave 35% yield of (i )-2-hexanol with 68% ee.45... 

Although addition of activated phosphoramidite to hemiacetals of manno-pyranoses under thermodynamic control has been reported to deliver exclusively a-phosphates in some cases,43 anomeric mixtures with preponderance of a-anomer have been reported in other examples.10,44 Since formation of phosphorotetrazolidite is a rate-limiting step of the process, initial activation of phosphoramidite followed by addition of nucleophilic hemiacetal should accelerate condensation and favour the formation of the thermodynamic a-product. Indeed, reaction of hemiacetal 101 with dibenzyl phosphorotetrazolidite assured exclusive a-selectivity of the resulting glycosyl phosphate 102.43 The accumulation in the reaction mixture of mildly acidic 1H-tetrazole, which is liberated upon reaction of tetrazolidite with hydroxylic component, could also favour predominant formation of the a-phosphate (Scheme 18, A). Conventional hydrogenolysis afforded the a-mannosyl phosphate 103. 

Except for one recent example, all iridium-catalyzed allylic substitution reactions have been performed under an inert atmosphere with dry solvent and reagents. The iridium metalacycle is sensitive to protonation, which opens the metalacycle and results in the formation of a less-active complex containing a K -phosphoramidite ligand. A paper by Helmchen et al. addressed this issue [107]. Nearly all iridium catalysts used for allylic substitution consist of an iridium fragment chelated by COD. In the presence of a catalyst containing dibenzo[a,c]cyclooctatetraene (dbcot) in place of COD, allylic substimtion reactions occur in air with results that are comparable to those of reactions performed under an inert atmosphere (Scheme 35). 

Example 7 the bis(2,4-dinitrophenyl)phosphoroamidite which can be prepared by a standard procedure reacts with alcohols in a non-selective way which leads to a mixture of products [28]. From a mechanistic point of view this result is consistent with spontaneous displacement of a 2,4-dinitro-phenoxy group in the reaction with alcohol which liberates free DNP. The latter activates the amino group allowing further ligand exchange. However if phosphitylation by the bis(2,4-dinitrophenyl)phosphoroamidite is performed in the presence of one equivalent of triethylamine, high chemoselec-tivity is observed, and the nucleoside (2,4-dinitrophenyl)phosphoramidite is formed in over 92% yield. 

For the copper-catalyzed 1,4-addition to 2-cyclohexen-l-one, other alkylmetal reagents have also been employed, achieving high enantioselectivity in some cases [Eqs. (3.2)-(3.4)]. Recently, one example appeared that utilized diphenylzinc as the nucleophile in the presence of phosphoramidite ligand 1 to produce highly enantio-enriched 3-phenylcyclohexanone [Eq. (3.5) 94% ee]. ... 

For examples of asymmetric catalyses with BlNOL-derived monodentate phosphites, phosphonites, and phosphoramidites, see a) M. T. Reetz, G. Mehler, Angew. Chem. 2000, 112, 4047 Angew. Chem. Int. Ed. 2000, 39, 3889 ... 

For phosphoramidite ligands bearing tropisomeric diols see, for example (a)... 

The drawbacks of the synthetic approach include the effort in preparation of the spin-labeled phosphoramidites and exposure of the spin label to the conditions of the chemical synthesis. The latter also applies for methods that use on-column modification during the synthesis (Piton et al., 2007 Schiemann et al., 2004). For example, the iodine solution that is commonly used for the phosphorous oxidation during the synthesis reduces nitroxides... 

Spiegelmers are a new class of substance for a wide field of applications, especially drug design. Their functional properties can be compared with the action of monoclonal antibodies. The production of spiegelmers is as simple as the synthesis of other oligonudeotides because standard chemical methods, for example common phosphoramidite chemistry, can be employed. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

Other examples of 7-membered ring heterocycles with three heteroatoms in the ring include the chiral titanium complex 311 [01SL1889], the novel phosphoramidite ligand 312 [01SL1375], and the cyclipostin natural products from a Streptomyces species (e.g. Cyclipostin N, 313), which is a hormone-sensitive lipase inhibitor [02JAN480]. 

Once again, the zinc enolates generated in the conjugate addition can be trapped with various electrophiles besides protons. For example, reaction of the enolate 270 obtained by treating cyclohex-2-enone with dimethylzinc in the presence of Cu(OTf)2 and phosphoramidite 269 with trimethylsilyl triflate and diiodomethane provided the cyclopropanation product 271 with good diastereoselectivity and high enantiomeric excess and chemical yield... 

It is evident from the previous examples that most copper catalysts have been applied only to simple, unsubstituted Michael acceptors so far. Only very recently, chiral, substituted cyclohex-2-enones were used as substrates for copper-catalyzed enantioselective 1,4-additions with phosphoramidites as the chiral ligand. Thus, highly enantioselective kinetic resolutions of several 4- or 5-substituted cyclohex-2-enones were reported by Feringa and co-workers.236,236a In contrast to these Michael acceptors, the corresponding 6-substituted cyclohex-2-enones possess a stereogenic center which can be... 

The so-called peptide nucleic acids (PNAs) 2.67 (140-142) are examples of the replacement of the entire sugar-phosphate backbone with different functionah-ties that retain biological activity. The chemistry is similar to SP peptide synthesis employing Boc or Fmoc protocols (see Section 2.1). Peptide-ON hybrids, where either one (143) or two (144) of the ON termini are attached to peptide chains, have been reported. Acyclic silicon phosphoramidites 2.68 (145) have also been used for SPS of silicon-containing ON analogues. 

Finally, when aziridines bear a 2-alkenyl substituent, they can engage in an SN2 reaction with dialkylzinc reagents using copper catalysts. Enantioselectivity can also be induced by including a chiral ligand, such as the binaphthyl phosphoramidite 174. For example, the aziridinyl cyclohexane 175 provided exclusively the trans-, 4 adduct with 83% ee upon treatment with dimethylzinc in the presence of copper(II) triflate and ligand 174 <03TL8559>. 

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