Radical addition phosphinic acid

Commercial phosphine derivatives are produced either by the acid-cataly2ed addition of phosphine to an aldehyde or by free-radical addition to olefins, particulady a-olefins. The reactions usually take place in an autoclave under moderate pressures (<4 MPa (580 psi)) and at temperatures between 60 and 100°C. 

There are a few economical routes that can be employed for production of the largest-volume phosphines as specialty chemicals. The preparation of alkyl phosphines, where R > C2H, employs the addition of lower phosphines across an olefinic double bond. The reaction may be either acid-, base-, or radical-catalyzed. The acid-catalyzed addition probably proceeds through the generation of a carbonium ion intermediate which is attacked by the unshared... 

Some approaches to the synthesis of 2- and 3-phosphonomethyl derivatives of D-arabinose are covered in Chapter 14, and the generation of a dialkyl phos-phonodithioyl radical from 7 and its addition to carbohydrate alkenes has allowed the synthesis of other C-phosphonomethyl-substituted sugar derivatives (Scheme 1). The phosphinic acid analogue 8 of cychc AMP has been prepared, and the olefin metathesis reaction, with a newer Grubbs catalyst, has been used to synthesize some carbohydrate cyclic phosphonates, e.g. 9. ... 

In order to activate or enhance the activity of group III of the metabotropic glutamate receptors, new and potent phosphinic agonists were synthesized by Acher et al. in 2007 [54], Indeed, these presynaptic receptors inhibit the adenylate cyclase and the release process. y-Phosphinic acid derivative 49 is the key intermediate for the formation of compounds 51,52 and 53 (Scheme 7). Starting from a radical addition of hypophosphorous acid to the IV-CBz protected vinylglycine methyl ester 48, the phosphinic derivative compound 49 was obtained in 94%... 

Another strategy was performed for phosphinic acid 54c. First, a radical addition of H3PO2 on unactivated diethylallylmalonate afforded regioselectively the terminal adducts 58 and 58. The next steps were identical to the first method giving a yield inferior to 5% (Scheme 9). 

Both mono and dichlorides can be obtained by treating phosphorus trichloride with dialkyl-phosphinous and alkylphosphonous esters, respectively (6.145, 6.146), or with primary phosphinic acids (6.213). The addition of terminal alkenes to PCI3 under free radical conditions produces P-chloroalkylphosphonous dichlorides (6.147). 

A plethora of 2-substituted 0,0-bis(trimethylsilyl) alkylphosphonites, their analogues and functionalised derivatives have been prepared by nucleophilic or free-radical additions to bis(trimethylsiloxy) phosphine. Silyl phosphonites (16), formed in situ by the addition of bis(trimethylsily) hypophosphite to the corresponding a-substituted acrylates, styrene or vinyl phosphonates were used for the preparation of pseudo-y-aminobutanoyl peptides and other phosphinic analogues of y-aminobutyric acid in an Arbuzov reaction with A-(o)-bromoalkyl)phthalimides. The Michaelis-Arbuzov reaction of ethyl a-bromo-a-fluoro- and a,a-difluoroacetates with dialkyl phenylphosphonite was reported to furnish unusual products (17)... 

AIBN initiates the radical addition of RgSnH to vinyl phosphines, the reduction of monochloromethyl polycyclic benzenoid hydrocarbons by PhgSnH, and of the isonitrile intermediate formed in the deamination of amino-acid esters. ... 

Deprele S, Montchamp J-L. Triethylborane-initiated room temperature radical addition of hypophosphites to olefins synthesis of monosubstituted phosphinic acids and esters. J. Org. Chem. 2001 66 6745-6755. 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Reactions of silanes are often best catalyzed by hydrosilation catalysts such as Pt or Pd. Similarly, C — H bonds are formed in the addition of phosphines or amines to C = C or C = C bonds. Reactions are catalyzed (acid, base, or metal) or free radical promoted, e.g. ... 

One of the many important differences between phosphorus and nitrogen chemistry is the relative strengths of their bonds to hydrogen. The relatively weak P—H bond means that this functionality can be added across a wide variety of unsaturated molecules (alkenes, alkynes, carbonyls) and hence this represents an excellent method for preparing tertiary phosphines. The addition of P 11 compounds to C=0 and C=N has been described in detail by Gilheany and Mitchell.2 The reaction can be catalyzed by base (potassium hydroxide, butyllithium), acid (HC1, carboxylic acids, sulfonic acids, boron trifluoride), free radical (uv, organic peroxides, AIBN) or metal (simple metal salts, late transition-metal complexes). In some circumstances no catalyst is required at all for P 11 additions to proceed.60... 

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