Phosphonium salts stereochemistry

Most of the problems related to the phosphonium salts stereochemistry are discussed under synthesis (Section II), reactivity (Section III) and spectrometric characteristics (Section I.C.). Because of the tetrahedral geometry of phosphorus, chirality arises from the presence of four different substituents. Enantiomeric forms may be separated by... 

Allylphosphonium salts are synthesized by substitution of allyl halides with PPh3. The use of allyl alcohol, allyl acetate, or nitropropene with a palladium catalyst has also been reported.19 It is shown in this study that the organophosphorous compounds can be obtained by a palladium-catalyzed addition to an allene. A notable aspect of this method is that it can control the stereochemistry of the phosphonium salt, and that (Z)-allylphosphonium salts have been obtained in pure form for the first time. 

Reactions.—Alkaline Hydrolysis. The first total resolution of a heterocyclic phosphonium salt containing an asymmetric phosphorus atom (128) has been reported, providing ready access to optically active phospholan derivatives of value for studies of the stereochemistry of nucleophilic displacement at phosphorus.124 Alkaline hydrolysis of (128) proceeds with retention of configuration at phosphorus to form the oxide (129). Stereochemical studies in the phospholan series have also been facilitated by the X-ray investigation125 of an isomer of l-iodomethyl-l-phenyl-3-methylphospholanium iodide, which is shown to have the structure (130). 

With the correct Cl5 stereochemistry established, Wittig reaction of 53 with known phosphonium salt 52 followed by saponification completed the synthesis of northern half building block 64 (Scheme 10) [50]. 

When the stereochemistry of the reaction was investigated87, it was established that the reaction is fully stereospecific the Z or E stereochemisty of the starting / -bromovinyl sulphone remains preserved in the resulting phosphonium salt (reaction 31). 

TABLE 15. Stereochemistry of alkaline hydrolysis of phosphonium salts with a good leaving group... 

Preparation, properties and reactions of phosphonium salts TABLE 19. Stereochemistry of the alkaline hydrolysis of cyclic phosphoniums salts... 

This type of disconnection is mainly used for the preparation of dipeptides of type Xaai >[ , CH=CH]Gly. It allows control of the stereochemistry of the Xaa residue by starting from chiral a-amino aldehydes. For the construction of the /ram -p,y-unsaturated carboxylic acid moiety, the use of the triphenylphosphonium salt 31 (Scheme 9) derived from 3-chloro-propanoic acid was not suitable.14 Instead, the trimethylsilylprop-2-ynyl phosphonium salt 33 serves as a three-carbon unit, which can be converted into the P,y-unsaturated acid by hydroboration and oxidation. The required Boc-protected a-amino aldehyde 32 can be prepared using virtually racemization-free procedures. 37 However, at the end of the reaction sequence, racemization has been detected, especially for Boc-Phet )[ , CH=CH]Gly-OH, but not for the Ala and Pro analogues. 63 A mixture of E- and Z-enynes 34 and 35 is formed (8 2 to 9 1), which can be separated by column chromatography. 4,48 50 53 64 65 ... 

We have simulated the steric course of the alkaline hydrolysis of chiral five- (12) and six- (13) membered cyclic phosphonium salts, whose reaction kinetics and product stereochemistries had been studied previously by Marsi and coworkers (14,15). For this purpose, we determined the absolute configuration of the phospholan-ium iodide (12), and the x-ray structures of the related phos-thorinanium salts, 4 and (13). 

The diol 70 could also be made by dihydroxylatiou of the alkene 73 that might be made by a Wittig reaction from the phosphonium salt 72. As the stereochemistry of neither the alkene 73 nor the diol 70 is relevant to the synthesis of 71, no control is discussed. 

The choice of which way round to do the Wittig may appear arbitrary but it isn t. Pempo and his group7 chose citronellal 47 and citronellol 48, two related natural terpenes from citronella oil, as starting materials with the right stereochemistry at the one chiral centre. If you imagine a Wittig reaction between the phosphonium salt 49 and some suitable aldehyde, you will see that the central part of the molecule would be right. 

However, the aldehyde cannot be citronellal as the stereochemistry would be wrong. In addition, both terminal alkenes must be oxidised away so that the rest of the molecule may be attached. So this is what they did the left-hand half of the molecule was assembled from citronellol 48 by oxidation to the aldehyde 50 and the remaining seven carbon atoms added by a Wittig reaction. The product is mainly Z-51 but this is irrelevant as the alkene will disappear. The phosphonium salt is ready for coupling to the right-hand half. 

When generating the ylide from the corresponding phosphonium salt, the choice of the method of formation is important for the stereochemistry of the reaction. With the original application of lithium alkyls as bases one equivalent of lithium halogenide is always formed this lowers the stereoselectivity. Not before the development of methods for the preparation of salt-free ylide solutions, such as the sodium amide... 

Samaan used reduction at a mercury cathode to convert the phosphonium salt 33 to the phosphine (34) (79PS89). This gave the opposite stereoisomer from that available as the major product (35) from base hydrolysis followed by silane reduction. The stereochemistry of each compound was established by NMR analysis. 

The following reaction between a phosphonium salt, base, and an aldehyde gives a hydrocarbon Q Hi2 with the 200 MHz NMR spectrum shown. Give a structure for the product and comment on its stereochemistry. You are not expected to discuss the chemistry ... 

By comparison with the Homer-Wittig reaction, the Julia alkenation has two principal assets. First, as the nucleophilic partner in the connective step (stage 2), sulfones are used, which are often more readily available and more easily purified than the corresponding phosphonium salts. Secondly, the 1,2-disub-stituted alkenes produced in the key reductive elimination step have predominantly ( )-stereochemistry. One detraction of the Julia alkenation is its length — it can be foiled at any one of the four stages. In practice, stage 2, the condensation of the metalated sulfone with the carbonyl, is usually the most problematic but in certain circumstances all of the stages have their pitfalls. These will be examined individually below. 

An extensive study of the stereochemistry of alkaline hydrolysis of a range of acyclic phosphonium salts under various reaction conditions has been reported. In general, the presence of bulky groups at phosphorus, as in the salts (133), leads to hydrolysis with predominant retention of configuration at phosphorus, whereas the salts (134) undergo hydrolysis with almost complete inversion of configuration. 

These ylids are classified as semi-stabilised or of intermediate reactivity, and their stereoselectivity may be poor.43 If the stereochemistry of the double bond in the ylid (from 167) is E, this is generally retained in the product, but if it is Z, as in the ylid derived from 170, low temperatures are needed to stop rotation at the allyl ylid stage. At -25 °C less than 5% -171 is formed in the synthesis of vitamin D metabolites.44 The stereochemistry of the new double bond is generally not well controlled, 1 1 ratios of E Z are not uncommon, but Vedejs finds that phosphonium salts such as 172 with two phenyl and two allyl groups give good yields of T-dicncs45 such as 173. 

Microreactor technology has also been applied in some reactions to be able to more accurately control the stereoselectivity of reactions. Skelton and coworkers have reported the application of microreactors for the Wittig reaction [14, 35], The authors used the microreactor to prepare the cis- and tr ns-nitrostilbene esters 19 and 20 using the Wittig reaction (Scheme 14.6). Several features such as stoichiometry and stereochemistry were investigated. When two equivalents of the aldehyde 22 to the phosphonium salt 21 were used in the reaction, a conversion of 70% was achieved. The microreactor demonstrated an increase in reaction efficiency of 10% over the traditional batch synthesis. The reaction stoichiometry... 

---