Phosphorus compounds, asymmetric

Bergin E, O Connor CT, Robinson SB, McGarrigle EM, O Mahony CP, Gilheany DG (2007) Synthesis of F-stereogenic phosphorus compounds. Asymmetric oxidation of phosphines under Appel conditions. J Am Chem S[Pg.228]

Organophosphorus compounds. Phosphorus-carbon bond fonnation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or tritlates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diarylphosphi-nates 780, 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Tnmethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Aaron, H.S., Uyeda, R.T., Frack, H.F., and Miller, J.I., The stereochemistry of asymmetric phosphorus compounds. IV. The synthesis and stereochemistry of displacement reactions of optically active isopropyl methylphosphonochlo-ridate, /. Am. Chem. Soc., 84, 617, 1962. 

In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

For these and other reasons, the development of asymmetric catalytic methods for the preparation of enantiopure phosphorus compounds is highly desirable. One approach is to perform hydrolytic kinetic resolution using phosphotriesterases as catalysts (152-154). A typical example is the production of chiral organophosphates (K)-yi or (5)-37. 

Chiral Phosphorus Compounds Koizumi et al. 251 have prepared a series of chiral organophosphorus compounds (256) in which the phosphorus atom is the asymmetric center, whereby amino acid derivatives were used as chiral auxiliary reagents. 

H. B. Kagan, Chiral Ligands for Asymmetric Catalysis, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 5, Chap. 1, Academic Press, New York, 1985 H. B. Kagan and M. Sasaki, Optically Active Phosphines Preparation, Uses and Chiroptical Properties, in F. R. Hartley, ed., The Chemistry of Organo-phosphorus Compounds, Vol. 1, Chap. 3, John Wiley Sons, New York, 1990. 

Soai [8], Bolm [9], Feringa [10], and Alexakis [11] have reported nickel-or copper-catalyzed asymmetric conjugate addition of diethylzinc, with chiral amino alcohols or a chiral trivalent phosphorus compound (Scheme 8D.2). 

Branching of the O-alkyl ester chain of organo-phosphorus compounds may introduce an asymmetric center, which together with an asymmetric substituted phosphorus atom creates a number of stereoisomers. Diastereoisomers may even be separated on a conventional capillary GC column. This is, for instance, the case with the nerve gas soman, which usually produces two peaks in a gas chromatogram. Although this is characteristic for identifying soman, it also increases the GC/MS detection limit by a factor of two. 

One of the most popular DQ sequences commonly used in the study of organic and bioorganic phosphorus compounds is the C7 sequence and the permutation-ally offset stabilised variant of C7 (POST-C7).51 Figure 10A shows, in pictorial form, the pulse sequence and DQ coherence pathway. Figure 10B displays the SQ-DQ 31P-31P POST C7 spectrum of the disodium salt of ATP trihydrate recorded at 10 kHz MAS.52 The correlation peaks between a. and [ > as well between / and y phosphorus centres confirm the presence of two molecules in the asymmetric units and show the connectivity between them. 

Enantiomerically pure phosphines are frequently employed as ligands in transition-metal-catalyzed asymmetric reactions. For this reason, various methods have been designed for their preparation.1 Many of them involve the use of borane adducts of trivalent phosphorus compounds,2 in which the borane moiety mainly acts as a protecting group. These Lewis adducts are easily prepared and stable to air, and several methods have been designed to cleave them. 

Asymmetric addition of phosphorus compounds to C-N double bonds has been widely studied and mainly concerns the synthesis of chiral a-aminophosphonic acids (for reviews on the synthesis of aminophosphonic acids, see refs 36, 37 and 67). For this purpose, the following types of organic nitrogen compounds have been used aldimines and cyclic imines, nitrones, ureidoimino derivatives and imidothioloesters. A separate example is the addition of dialkyl phosphites to hydrazones, which was used for the synthesis of phosphonosugars. 

Asymmetric Coiyugate Addition of Allyl- and Crotylphosphonamides/ The asymmetric C-allylation of a, 3-unsaturated carbonyl compounds is a powerful tool for the functionalization of a carbonyl compound in the P-position. Since such a process normally leads to the corresponding enolate derivative when anionic reagents are used, there exists the possibility of trapping with an electrophile. Thus sequential addition and trapping can lead to vicinally substituted carbonyl compounds. Asymmetric allylation has been achieved previously with simple cycloalkenones using phosphorus and sulfur based reagents that must be prepared in diastereomerically pure form. 

Studies of the asymmetric synthesis of chiral phosphorus compounds, (100) via the destructive-selective oxidation of (99) with various camphor derived oxaziridines has been described (91CB1627). The des were mostly modest, for example 8-48%. 

Due to the great importance of phosphines and phosphinites as chiral ligands for asymmetric catalysis, several hundred compounds of this type have been prepared. In this section, only those compounds which have been mentioned in this Houben-Weyl volume will be discussed. Because of their close relation to the specific topics, biaryl phosphines have already been mentioned in Section 6 and ferrocene derivatives in Section 7.1. All other phosphorus compounds are treated here. An excellent review on the synthesis of enantiomerically enriched compounds where phosphorus is a stereogenic center has recently been published73. 

Pd-catalyzed arylation of various phosphorus compounds containing P—H bonds with aryl and alkenyl halides, or triflates offers useful methods of C— P bond formation. After pioneering work on Pd-catalyzed arylation and alkenylation of dialkyl phosphonates by Hirao etal., extensive studies have been carried out on arylation of various phosphorus compounds. The methods are particularly useful for the synthesis of various chiral phosphines used in Pd-catalyzed asymmetric reactions. 

Recent Advances in Asymmetric Synthesis of P-Stereogenic Phosphorus Compounds... 

The chlorophosphine boranes 97 are efficient starting reagents for the synthesis of various classes of P-chiral phosphorus compounds. Reactions of chlorophosphine boranes 97 with nucleophiles, such as carbanions, phenoxides, phenylthiolates, or amides, leads to the formation of corresponding organophos-phorus compounds 100-103 in yields of 53-99% and with up to 99% ee. This method was also used for the preparation of various classes of symmetric and asymmetric P-chiral ligands useful for asymmetric reactions, catalyzed by complexes of transition metals (Scheme 31) [52, 60, 61]. 

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