Phosphine oxides Michael addition

The Painter group developed another approach to tetramates (e.g., 320) that involved the reductive amination of y-oxobutenoates (e.g., 319) in the presence of primary amines (Scheme 81 2002S869). Unsaturated dicarbonyl 319 was prepared in three steps by the phosphine-catalyzed Michael addition of benzyl alcohol to butynoate 318, desilylation, and oxidation of the resulting primary alcohol with 2-iodoxybenzoic acid (IBX). Treatment of 319 with tert-butylamine followed by sodium borohydride gives the O-benzyl tetramate 320 via a reductive amination—lactamization. 

A Michael-type addition reaction of phosphine generated from red phosphorus in concentrated aqueous KOH solution has been noted to provide moderate isolable yields of pure organophosphorus products.27 For example, tris-(2-cyanoethyl)phosphine is produced in 45% isolable yield from acrylonitrile, and tris-(2-[y-pyridyl]ethyl) phosphine oxide is isolated in 40% yield from 4-vinylpyridine under these conditions. Excellent yields of the tertiary phosphine oxide, tris-(2-cyanoethyl)phosphine oxide, have been reported using white phosphorus in absolute ethanol with KOH at ice/salt-bath temperatures.28 A variety of solvent systems were examined for this reaction involving a Michael-type addition to acrylonitrile. Similarly, tris-(Z-styryl)phosphine is produced from phenylacetylene under these conditions in 55% isolated yield. It is noteworthy that this last cited reaction involves stereospecific syn- addition of the phosphine to the alkyne. 

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]. 

In contrast, phosphine oxides were later applied in Michael additions of silyl ketene acetals to cycHc and acychc a,P-unsaturated ketones promoted by 59a as scavengers of any catalytically active Me3Si species formed during the reaction (Scheme 5.80) [151]. Further, this methodology now allows the realization of an... 

If a nucleophilic addition at a carbonyl or imine carbon occurs, the product is still a phosphinate (from a phosphonous ester) or a phosphine oxide (from a phosphinous ester), but the reaction is commonly referred to as an Abramov or Pudovik reaction. An example of the Pudovik reaction is shown below (equation 16). Addition of the phosphorus nucleophile to the /3-carbon atom of an a, /3-unsaturated substrate (Michael addition) is commonly referred to as a hydrophosphinylation reaction. ... 

The Michael addition of secondary phosphine oxides to o ,/ -unsaturated esters proceeds with very high stereoselectivity. Thus, in the reaction of benzylphenylphosphine oxide with methyl ( )-2-methyl-2-butenoate, only two of the four possible diastereomers (PR)-7 and (P51)- are formed and in a 1 1 ratio they have the same relative configuration at the 1- and /1-carbon atoms, but differ in the configuration at phosphorus10. 

Michael addition of secondary phosphine oxides to cyclohexene-1-carboxylates (both flexible and biased) gives exclusively the axially substituted products 810. 

The red metastable product, produced from P4 and KOH or KOEt, does not appear to be an intermediate in these, tertiary phosphine oxide syntheses, since when separately prepared, gave only minor amounts of phosphine oxide. This result indicates that the olefinic compounds must attack an earlier intermediate. The initial step was thought to involve nucleophilic attack of hydroxide ion on tetrahedral white phosphorus to give a phosphide ion that subsequently underwent a Michael-Addition to the electrophilic unsaturated compounds present (Rauhut, Bemheimer and Semsel). 

However, during the addition of -keto esters onto enals, ytterbium triflate proved to be an efficient catalyst [171] as in the Michael additions of a-nitro esters [172]. Several water-soluble phosphines gave the corresponding phos-phonium salts in good yields when added to a,j9-unsaturated acids [173] or activated alkynes [174]. With alkynes, vinyl phosphine oxides or alkenes were formed depending on the pH of the aqueous solution. Significantly, the reaction of nitroalkanes with buten-2-one is considerably accelerated when going from... 

Michael addition of secondary phosphines on conjugated olefins is a well known reaction in organic synthesis. Accordingly, addition of diphenylphosphine on hydrophilic activated alkenes in CH3CN or in CH3CN/H20 solution leads to various tertiary phosphines [33] examples include 1, 25, 27. In order to avoid the formation of phosphine oxides and/or the hydrolysis of some alkene derivatives (e.g. acryl esters) a small amount of Et N+OH" was used as base, and a small quantity ofditertbutylphenol was... 

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... 

The previously accepted pathway consisted of P-H oxidative addition to Pt(0) to form 19 followed by coordination and insertion of the alkene in the Pt-P bond to form 20 and a final reductive elimination to furnish the product and regenerate the catalyst. Another possibility is the nucleophilic attack of phosphido complex 19 to the alkene ( Michael addition mechanism, as in anionic polymerisation) to generate the zwitterionic intermediate 21. This complex can yield the hydrophosphination product 11 via one of two complementary pathways. Carbanion attack at the cationic platinum hydride i.e. intramolecular hydrogen transfer) would yield the final phosphine complexed to Pt(0) that would be displaced by an equivalent of PHR R to furnish, after oxidative addition, starting complex 19. Alternatively, the anionic carbon atom in 21 could attack the platinum centre directly, forming the cyclic intermediate 22. From here Pt-P bond dissociation would generate 20, which would furnish the product after reductive elimination. 

Excellent stereoselectivities (<99 1 dr and <99% ee) have been attained for the Michael addition of ketones to nitroalkenes, catalysed by the polyfunctional secondary-secondary-tertiary triamines (216) and (217). ° The proline-derived phosphine oxide (218) also exhibited a high level of stereocontrol (<99 1 dr (syn/anti) and <96% Catalyst (219) has been designed computationally for... 

Phospha-Michael reactions are useful to establish a P-C bond. The addition of >P(0)H species (e.g., dialkyl phosphites and secondary phosphine oxides) at the end of electron-poor double bonds may be facilitated by bases, like NaOR, NaOH, or DBU [56]. The addition of P-heterocyclic nucleophiles was also studied. Dibenzo[c.e][l,2]oxa-phosphorine oxide (36) added easily on the double bond of methyl vinyl ketone xmder MW conditions in the absence of any solvent (Scheme 12) [57]. 

E. Balint, J. Takacs, L. Drahos, G. Keglevich, Microwave-assisted phospha-Michael addition of dialkyl phosphites, a phenyl-H-phosphinate, and diphenylphosphine oxide to maleic derivatives. Heteroatom Chem. 23 (2012) 235-240. 

The development of transition metal-free hydroelementation reactions has been a goal for the synthetic community for many years. As mentioned in the previous sections on Michael addition reactions, A-heterocyclic carbenes have been shown to be efficient catalysts for these addition reactions. One of the challenges that must be overcome when using these catalysts is the sensitivity of the catalysts to electrophiles. To circumvent this problem, carbon dioxide adducts have been synthesized and used as precatalysts for the phospha-Michael addition of secondary phosphine oxides to activated alkenes (Scheme 4.45) [96]. The success of this approach hinged on the observation that these adducts underwent cleavage in solution to generate the free carbene and carbon dioxide. The concentration of the free carbene was found to be dependent upon the solvent, and THF was found to be an effective solvent for the... 

In 2012, Keglevich and coworkers reported the catalyst-free synthesis of a series of new >P(0)-substituted maleic derivatives (62) via microwave-assisted phospha-Michael addition of diall l phosphites, ethyl phenyl-H-phosphinate, and diphenylphosphine oxide to Al-phenyl and N-methyl maleimide (61), in most of the cases without any solvent, in good yields (71-98%) and within 3 h (Scheme 29). This method is advantageous over the previously reported method of Jiang et al. in terms of using no solvent or catalyst. 

Phosphorus nucleophiles Asymmetric Michael addition of diaryl phosphine oxides to a,/ -unsaturated A-acylated oxazolidinones (299) has been reported to proceed with excellent enantioselectivities (<99% ee) in the presence of a catalyst generated from Et2Zn and the polydentate ligand (301). °... 

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