Secondary phosphites substitution reactions

The synthesis of nucleoside-derived pyridylphosphonates under metal-free conditions was reported (Scheme 4.216) [355]. The chemistry was operationally straightforward and entailed treatment of a nucleoside-derived secondary phosphite with pyridine/trityl chloride and DBU to generate the arylphosphonates in excellent yields. It was noteworthy that the reaction was regioselective for substitution at the 4-position of the pyridine moiety. Based upon an investigation of potential intermediates, the mechanism was proposed to proceed through the initial generation of an A-tritylpyridinium ion. Reaction of this species with the secondary phosphite and DBU afforded a dihydropyridine intermediate that could be observed by NMR spectroscopy but could not be isolated as it underwent conversion... 

This has been accomphshed by simply substituting a secondary phosphite for the phosphine oxide in the metal-free coupling reaction [541]... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

Substituted a-haloacetonitriles (R H, Scheme 6.3) are exceptions to the rule that branched-chain halides are unreactive in Michaelis-Arbuzov reactions. A variety of a-bromo nitriles react with triethyl phosphite at reflux to produce a-substituted cyanomethylphosphonates in fair to good yield (40-76%, Table 6.1). Because the reaction conditions are rather severe, the reanange-ment is governed by the thermal stability of the secondary bromoacetonitriles, and prolonged heating does not increase the yield. 

Substituted haloacetates (R and R 7 = H) are exceptions to the rule that branched-chain halides are unreactive in the Michaelis-Arbuzov reaction. A large variety of easily available a-chloro or bromo esters "- react with trialkyi phosphites at 160-190°C to produce a-substituted phosphonoacetic esters in fair to excellent yields (31-96% , Scheme 8.7, Table 8.2). Because secondary a-haloacetates are stable compounds that may be either easily prepared on laboratory scale or may be obtained commercially, the Michaelis-Arbuzov rearrangement appears as a reaction of special importance. 

Replacement of one C-substituent in phosphines by an alkoxy or aryloxy group produces esters of phosphinous acid (phosphinites). Further substitution of alkyl or aryl by oxy groups gives first the diesters of phosphonous acid (phosphonites) and finally triesters of phosphorous acid (phosphites). Secondary phosphine oxides (SPOs) or heteroatom-substituted phosphine oxides (HASPOs), which are derived from the corresponding free acids by tautomerism, have been only occasionally investigated as ligands. However, they play a pivotal role as hydrolysis products of esters. In this role, they may exert an impact on the catalytic reaction. 

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