Michael phospha

Terada expanded the phospha-Michael reaction to include diphenyl-phosphites [128]. A novel binaphthol-derived guanidine catalyst promoted the addition in high yields and enantioselectivities (Scheme 73). Functionalizing the external nitrogen with a diphenylmethine moeity enhanced selectivities for a large scope of nitro-olefm derivatives. 

Tan also found that guanidine 21, acting as a base to activate the o [3], X [3] tautomers of diaryl phosphine oxides, catalyzes the asymmetric phospha-Michael reachon of aryl nitroalkenes (Scheme 5.42) [76]. He later employed 21 to realize highly enantioselective Michael additions of dithiomalonate and 3-keto thioesters with a range of acceptors, including maleimides, cyclic enones, furanone, and acyclic 1,4-dicarbonylbutenes [77]. 

Scheme 1.1.13 Solid-base-mediated phospha-Michael additions.

Asymmetric synthesis of P-phosphono-malonates via K0H/Fe203 catalyzed phospha-Michael reaction to Knoevenagel acceptors has been achieved by Enders and Tedeschi [57]. The reaction did not proceed when only KOH was used as a catalyst Fe203 was the best diastereoselective support among the other supports tested, A1203, ZnO, Cu20, Mn02 and MgO. 

Alkyl phosphonates are prepared smoothly by TMG (1) catalysed aldol-type addition of dialkyl phosphites to ketones and imines under mild conditions [28] (Scheme 4.9). Dialkyl phosphites can also serve as good nucleophiles for Michael addition (phospha-Michael Reaction). 

The phospha-Michael reaction has been the last hetero-Michael reaction to be developed under iminium activation. In addition to the selectivity issues that have to be addressed, the identification of a suitable phosphorous nucleophile has been the most difficult task to overcome when developing the reaction because of the high tendency of phosphines toward oxidation in the presence of air. The first example was developed independently by Melchiorre and... 

Scheme 3.37 Enantioselective phospha-Michael reactions between diphenylphosphine and a,P-unsaturated aldehydes.

For a leading review on the asymmetric phospha-Michael reaction see D. Enders, A. Saint-Dizier, M.-I. Lannou and A. Lenzen, Eur. J. Org. Chem., 2005, 29. 

Scheme 4.74 The catalytic enantioselective phospha-Michael reactions using cinchona alkaloid-based catalysts.

Heteroatom nucleophiles were described less often. Ye and coworkers published a phospha-Michael addition catalysed by prolinol silyl ether catalyst. Another method for constructing a new C-N bond is the aza-Michael addition, that is the addition of nitrogen-based nucleophiles to a,(3-unsaturated aldehydes. Several groups published these type of reactions using diatylprolinol silyl ether as catalyst. " Fustero and coworkers used this reaction as a key step in the synthesis of biologically active chiral heterocycles. Recently, the authors showed the synthesis of quinolizidine alkaloids, such as (-l-)-myrtine, (-)-lupine and (-l-)-epiquinamide. Vicario applied 5-mercaptotetrazoles as nucleophiles towards a range of unsaturated aldehydes. The reaction proceeded via the iminium activation. The... 

An interesting approach to this direction was recently based on an Ireland-Claisen rearrangement triggered by the phospha-Michael addition of silyl... 

Subsequently, the highly enantioselective Michael addition of malonates and 1,2,4-triazole to cyclic and acyclic enones, as well as the first phospha-Michael reaction of cyclic enones and diaryl phosphine oxides was reported using a similar catalyst.In 2012, Huang, Wang and coworkers demonstrated that primary amine-thiourea 39 can efficiently catalyse the... 

Numerous guanidine-catalysed asymmetric Michael reactions and its related variants such as aza-Michael, oxa-Michael, phospha-Michael, sulfa-Michael have been reported in the literature. A nonexhaustive selection of conjugate addition reactions that is relevant to green chemistry will be presented. Glycine imines are commonly employed in Michael additions. They are protected a-amino acids and must he deprotected if an amino acid derivative is desired (Scheme 23.5). The large molecular mass of the imine group then makes waste generation a problem. 

A green synthetic protocol under solvent-free conditions for the synthesis of phos-phono malonates (162) from alkenes (160) and phosphorous nucleophiles (161) using nanoflake ZnO at 50°C has been documented (Scheme 9.52) (Hosseini-Sarvari and Etmad 2008). The reaction is an example of one of the most powerful and important C-P bond-forming reactions, which is the phospha-Michael addition. The advantages of this method include mild reaction conditions, a simple set up, high yields, and so on. The formylation of amines (163) with formic add (70) under solvent-free... 

SCHEME 13.60 Knoevenagel condensation/phospha-Michael addition/double cyclization sequence for the synthesis of tetracyclic 2,3,4,lll7-tetrahydro-17/,67f-67, -[l, 2]benzoxaphospholo[2,3-fc][l,2]benzoxa-phosphol-l-ones 254 [98],... 

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