HWE olefination

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

Step 1 Homer-Wadsworth-Emmons (HWE) olefination provides the (is)-vinyl... 

The aldehyde was made by alkylation of the nitrile 45 and reduction (actually using ITAIH4, though we might prefer DIBAL), an HWE olefination and conversion of the ester 46 into the ketone 42. Finally, the rearrangement11 required 400 °C. 

The trisubstituted (Z)-olefin was introduced by Still-Gennari HWE olefination, as precedented by Schreiber [43, 44, 106], and following silyl protection provided 124. Conversion into the iodide 125 was followed by alkylation with the lithium enolate of aryl ester 126, to complete the C9-C16 subunit 121. The synthesis of the C17-C24 subunit 98 from 120 began with a four-step sequence involving protecting group manipulations and oxidation at C21 to provide aldehyde 127, converging with the earlier route to 98 [55-57],... 

A simple procedure for the preparation of trifluoromethylated vinyl- and dienyl-phosphonates with y-alkoxycarbonyl moiety of exclusively or predominantly (Z)-configuration (201) has been described. It involves acylation of ethyl-1,1-bisphosphonate (202) with trifluoroacetic anhydride, addition of selected Reformatsky reagents to the resulting 1-trifluoroacetyl-1,1-ethyl bisphos-phonates (203) and finally spontaneous Horner-Wadsworth-Emmons (HWE) olefination of the adducts (Scheme 55). " ... 

Acylation of a-lithio-a-phosphonylalkyl sulfides (440) with carboxylic acid esters was utilized as a facile route to a-alkylsulfenyl substituted p-ketophos-phonates (441). Keto-enol tautomerism of these new compounds in different solvents as well as regiochemistry of alkylation and acylation reactions and usefulness for HWE olefination reactions were studied (Scheme 104). ... 

An important addition to the Wittig tran -olefination procedure is the introduction of phosphonate-stabilized carbanions as olefin-forming reagents, referred to as the Horner-Wadsworth-Emmons or HWE reaction. The HWE olefination offers several advantages over the Wittig reaction using stabilized ylides ... 

The stereoselectivity of the HWE olefination reaction depends on the nature of the RO groups on phosphorus, structural features of the ylide, the solvent, and the reaction temperature. Generally, the HWE reactions give preferentially the more stable fran -disubstituted olefins. 

The mechanism of the HWE olefination is not fully understood. In the Still-Gennari modified HWE olefination the phosphorous has two electron-withdrawing trifluoroalkoxy groups. In this case the rearrangement from the chelated adduct to form the oxaphosphetane is favored and the elimination step is faster than the initial addition which essentially becomes irreversible (unlike in the case of the regular HWE olefination). As a result the formation of the (Z)-stereoisomer is predominant. 

In C.J. Forsyth s total synthesis of phorboxazole A, the intramolecular version of the Still-Gennari modified HWE olefination was used to affect the macrocyclization of a complex it>/s(trifluoroethoxy) phosphonate-aldehyde precursor. The precursor was dissolved in toluene and was exposed to K2CO3 in the presence of 18-crown-6. The desired C1-C3 (Z)-acrylate moiety was formed in 77% yield with a 4 1 (Z ) ratio. Interestingly, when the same cyclization was carried out with the regular /)/s(dimethoxy) phosphonate, the macrocyclization was markedly slower, but the stereoselectivity was the same (4 1). 

In the laboratory of S.V. Ley, the total synthesis of the 3-lactone cholesterol synthase inhibitor 1233A was achieved by using the oxidative decompiexation of a (jt-allyl)tricarbonyliron lactone as the key step. " The (Z)-alkene present in the target was introduced using the S-G modified HWE olefination of an aldehyde with b/s(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate to give the desired a, 3-unsaturated methyl ester in excellent yield. 

The stereoselective synthesis of the anti-ulcer 3,4-dihydroisocoumarin AI-77B was accomplished by E.J. Thomas and co-workers. The key transformation was the stereoselective dihydmxylation of 4-(Z)-alkenylazetidinones that were prepared from 4-formylazetidinone via the Still modified HWE olefination. The benzyl b/s(trifluoroethyl) phospho-noacetate was prepared from phosphonic dichloride and 2,2,2-trifluoroethanol and was alkylated using benzyl... 

HWE olefination Stereoselective olefination of aldehydes and ketones using phosphoryl-stabilized carbanions. 212... 

HWE olefination-Still modification Preparation of (Z)-a,P-unsaturated ketones and esters by coupling electrophilic b/s(trifluoroalkyl) phosphonoesters with aldehydes and ketones in the presence of a strong base. 214... 

Emmons (HWE) olefination strategy. Following deprotection and oxidation steps, the aldehyde 3 was reacted with lithiated resorcinol fragment 4. In order to best aid the key dearomatization step, we opted to tether the benzylic oxygen atom with one of the phenolic oxygens. This alleviated the use of an unstable triol and made the oxidation site more accessible. Unfortunately,... 

The beauty of our tetracyclic cage target is that the cyclization cascade can be initiated from the front (as we did in Scheme 14) or from the back (Scheme 15). Simply by changing the order of addition in terms of with what the phosphonate is alkylated and then what type of aldehyde with which it reacts, we could easily access substrates that allow a cyclization to proceed from either front or back. In our second attempt, we first alkylated the phosphonate with an allyl bromide (71) containing a vinyl iodide needed for cyclization and then subjected that product (72) to an HWE olefination. Again, we were delighted that this complex acrylic-type acid (74) could be delivered with lead(IV) acetate to form quinone ketal 75. Subsequent heating of this... 

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