A-phosphino ketones

Asymmetric Synthesis of a-Phosphino Ketones and 2-Phosphino Alcohols... 

In continuation of our efforts to explore the utility of the SAMP/RAMP hydra-zone methodology, we developed the first asymmetric synthesis of a-phosphino ketones via formation of a carbon-phosphorus bond in the a-position to the carbonyl group [70]. The key step of this asymmetric C—P bond formation is the electrophilic phosphinylation of the ketone SAMP hydrazone 87, giving rise to the borane-adduct of the phosphino hydrazone 88 with excellent diastereoselectiv-ity (de = 95-98%). Since these phosphane-borane adducts are stable with respect to oxidation, the chemoselective cleavage of the chiral auxiliary by ozonolysis leading to the a-phosphino ketones (R)-89 could be accomplished with virtually no racemization. Using RAMP as a chiral auxiliary, the synthesis of the enantiomer (S)-89 was possible (Scheme 1.1.25). 

There are many examples of the stereoselective addition of nucleophiles to carbonyl groups in which chelation to the titanium center should be critical—reported examples include the stereoselective hydride reduction of a- or /3-hydroxyketones (Eq. 305) [684-686], of a-phosphino ketones [687], of a-sulfonylketones [688], and of an a,/3-unsaturated carbonyl compound in a 1,4-fashion [689]. The stereoselective addition of organometallic compounds such as Grignard [669,690], zinc [691,692], copper [693], and other reagents [11] to carbonyl and related compoimds Ijy taking advantage of titanium chelation is a well established method in the stereoselective... 

P-Diketonesfrom %/i-epoxy ketones. 2 In the presence of this Pd(0) complex a,/ -epoxy ketones isomerize to /3-dikelones. An added ligand is usually necessary to avoid precipitation of palladium. The most satisfactory adjunct is l,2-bis(diphenyl-phosphino)ethane (dpe). The reaction is conducted in toluene at 80-140° for 10 100 hours. The isomerization is facile with strained epoxides it is sluggish with epoxides bearing an a-alkyl group. 

In another copper-catalyzed reaction, cross-coupling of alkynes with phosphi-ne-boranes was followed by surprising oxidation to yield ketones (Scheme 69) [122]. The active species was proposed to be a copper phosphido-borane complex, formed by proton transfer to a Cu-OH group. Formation of a Cu-acetylide followed by P-C reductive elimination would then yield a phosphino-alkyne, whose subsequent Cu-mediated air oxidation yields the ketone. 

The phosphino-oxazoline copper(II) complex (55) has also been found to be an effective catalyst[136] as have some titanium complexes, such as the extensively researched titanium-TADDOL system (56)[137]. A modified Ti(IV)-TADDOL compound is the catalyst of choice to promote Diels-Alder cycloaddition reactions between cyclopentadiene and alk-2-enyl phenylsulfonylmethyl ketones[138]. 

The (phosphino)(silyl)carbene 2a readily and cleanly adds to benzalde-hyde and cinnamaldehyde, affording the oxiranes 27 and 28, as single diaste-reomers.40 These results strongly suggest a concerted mechanism, since the formation of a zwitterionic intermediate, such as 29, would result in the formation of a phosphoryl alkene via oxygen atom attack at the phosphorus center. Note that 2a does not react with ketones, which is in line with its nucleophilic character. 

Tellers, D.M., Bio, M., Song, Z.J., McWilliams, J.C. and Sun, Y. Enantioselective Hydrogenation of an a-Alkoxy Substituted Ketone with Chiral Ruthenium (Phosphino-ferrocenyl)oxazohne Complexes. Tetrahedron Asymmetry 2006, 17, 550-553. 

Pinacolborane is extensively used in the borylation of aryl halides 114 in the presence of a base (typically pyridine or Et3N or KOAc) and catalytic amount of PdCl2(DPPF) to furnish aryl boronates 115 (DPPF = l,l -bis(diphenyl-phosphino)ferrocene Equation 7) <1997JOC6458, 2000JOC164>. Pinacolborane is compatible with esters, ketones,... 

Ruthenium complexes of chiral phosphines notably BINAP, 2,2 -bis(diphenyl-phosphino)-l,l -binaphthyl are very useful for industrial hydrogenations and H-transfer hydrogenation of alkenes and ketones. This is due to high turnover numbers and enantiomeric excesses (ee) of the products. A specific example41 of an... 

A good way to prepare p-diketones consists of heating a,p-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and l,2-bis(diphenyl-phosphino)ethane. ° Epoxides are converted to 1,2-diketones with Bi, DMSO, O2, and a catalytic amounts of Cu(OTf)2 at 100°C. a,p-Epoxy ketones are also converted to 1,2-diketones with a ruthenium catalyst or an iron catalyst. Epoxides with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of a ZnBr2 " or Tb(OTf)3 catalyst to give a y-hydroxy ketone. 

Ethylene and other olefins can also be copolymerized with carbon monoxide to form polymers of aliphatic ketones, using transition metal catalysts, like paUadium(ll) coupled with non-coordinating anions. There are numerous reports of such catalysts in the literature. One example is a compound composed of bidentate diarylphosphinopropane ligand and two acetonitrile molecules coordinating Pd coupled with BF3 counterions. This compound, bis(acetonitrile)palladium(II)-l,3-bis(diphenyl-phosphino)propane-(tetrafluoborate), can be illustrated as follows [97] ... 

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