Olivier Berger

A General Strategy for the Synthesis of P‐Stereogenic Compounds

A great leap forward toward the general synthesis of P-stereogenic compounds: Heating H3 PO2 with (-)-menthol and paraformaldehyde gives easily crystallized menthyl hydroxymethyl-H-phosphinate (1). From this product, virtually any P-stereogenic compound can be synthesized.

Manganese-mediated intermolecular arylation of H-phosphinates and related compounds.

The intermolecular radical functionalization of arenes with aryl and alkyl H-phosphinate esters, as well as diphenylphosphine oxide and H-phosphonate diesters, is described. The novel catalytic Mn(II) /excess Mn(IV) system is a convenient and inexpensive solution to directly convert Csp2 H into CP bonds. The reaction can be employed to functionalize P-stereogenic H-phosphinates since it is stereospecific. With monosubstituted aromatics, the selectivity for para-substitution increases in the order (RO)2 P(O)H<R(1) P(O)(OR)H<Ph2 P(O)H, a trend that may be explained by steric effects.

Chemistry of the versatile (hydroxymethyl)phosphinyl P(O)CH2OH functional group.

(Hydroxymethyl)phosphorus compounds are well-known and valuable compounds in general; however the use of (hydroxymethyl)phosphinates R(1)P(O)(OR(2))CH(2)OH in particular has been much more limited. The potential of this functionality has not yet been fully realized because the mild unmasking of the hydroxymethyl group was not available. The mild oxidative conversion of R(1)P(O)(OR(2))CH(2)OH into R(1)P(O)(OR(2))H using the Corey-Kim oxidation is described. Other reactions preserving the methylene carbon are also reported.

Phosphinate-containing heterocycles: A mini-review

Summary This review provides an overview of recent efforts towards the synthesis of phosphinate heterocycles R1R2P(O)(OR). Our laboratory and others’ have been involved in this field and as a result new P–C, P–N, and P–O containing heterocyclic motifs are now available through a variety of methods. While developing rapidly, this area is still in its infancy so that biological testing of the compounds has not yet been conducted and applications are rare. The growing availability of synthetic methods will undoubtedly change this situation in the near future.

Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols

The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the acids, and its mechanism is likely different. Various alcohols are examined in their reaction with phosphinylidene compounds R1R2P(O)H.

Development of a New Family of Chiral Auxiliaries

A new family of chiral auxiliaries designed on a conformationally restricted version of (-)-8-phenylmenthol has been developed. Both enantiomers are available from an inexpensive synthesis conducted on multigram scale. A first application has showed comparable diastereoselectivity between the novel auxiliary and (-)-8-phenylmenthol.

Manganese-Mediated Homolytic Aromatic Substitution With Phosphinylidenes

Carbon-phosphorus (C-P) bond-forming reactions via homolytic aromatic substitution (HAS) of non-functionalized substrates with phosphinylidene P(O)H compounds is becoming a useful synthetic tool for the preparation of aryl and heteroaryl phosphonates, phosphinates, and phosphine oxides. This review specifically covers recent work using manganese-mediated free radical processes. Several research groups employ expensive Mn(OAc)3 , whereas our own contributions focus on the novel and inexpensive Mn(OAc)2 /MnO2 system.