Through the Use of Organometallic Reagents

Information in this area is particularly sparse. Even when reverse addition methods are employed, low yields of dialkyl ethynylphosphonates are obtained for a dialkyl phos-phorochloridate and ethynylmagnesium bromide (reaction 35 R = RO, X = Cl). The use of a dialkyl phosphorofluoridate (230) (R = RO, X = F) with the same organometallic reagent obviates the need for reverse addition, and the overall yields are then improved . One more recently recorded example consists in the interaction of ethynylmagnesium chloride with methyl methylphosphonochloridate (230) (R = R = Me X = Cl) to give methyl ethynylmethylphosphinate  

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Acid chloride derivatives of phosphinous acids [R2POH] and phosphonous acids [RP(OH)2] have been mentioned previously (see Section 3.2) as precursors in the preparation of phosphines. In addition to the coimnon routes of preparation for these trivalent phosphoms acids, particularly through the use of organometallic reagents and Friedel Crafts reactions as noted, several other routes have been developed for their syntheses that are worthy of note. 

While technically not "organometallics," enamines are reagents that can provide nucleophilic carbon for new bond formation. Two groups of researchers have reported on the use of such reagents for the formation of new carbon-phosphorus bonds through displacement of chloride from phosphorus.72 73 For example, displacement of bromide from phosphorus tribromide has been used for the introduction of a new thiophosphoryl functionality adjacent to an original carbonyl group (Equation 4.28).72 This approach provides a facile access to (3-ketophosphonates. 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Measure the aliquot portion of the organometallic reagent with a pipette which has been previously warmed in the oven and allowed to cool with a stream of nitrogen flowing through it. The use of a suction bulb is essential. 

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