Intramolecular Homer—Wittig reaction

The formation of flve-membered cyclic imines through a Staudinger/intramolecular aza-Wittig reaction can also be performed by solid-phase synthesis and has been applied for the first synthesis of lanopylin Bi (108). The total synthesis, which takes only four steps, starts with a phase-transfer alkylation of diethyl 2-oxopropylphosphonate 105 with a 2-iodoethyl azide, affording the azido phosphonate 106, which undergoes a phase-transfer Homer-Emmons Wittig reaction with heptadecanal to provide the azido enone 107. An intramolecular aza-Wittig reaction of the enone 107 with polymer-supported triphenylphosphine in toluene completed the first total synthesis of lanopylin Bi (108) in 76% yield (Scheme 15.22). 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Wittig-Homer reaction with 1,4- and 1,5-dialdehydes.1 Reaction of these aldehydes with 1 equiv. of a Wittig-Horner phosphonate in an aqueous medium with K2C03 as base is accompanied by an intramolecular aldolization to provide five- or six-membered cycloalkenols. 

B. M. Heron, Heterocycles from Intramolecular Wittig, Homer and Wadsworth-Emmons Reactions, Heterocycles 1995, 41, 2357. 

The Wittig-like reactions are well known for C=C bond formation. An intramolecular process can serve as a ring closure and has been generally employed in the synthesis of numerous macrocyclic natural products [150]. Oishi and coworkers [151] applied this strategy to the synthesis of the aglycone (252) of the antibiotics venturicidins A and B. Thus, as shown in Scheme 84, the aldehyde phosphate 250 was subjected to the modified intramolecular Wittig-Homer condensation with a mild base, yielding the macrocycle 251 in 48% yield. 

The last example illustrates one advantage of this method the enol ether function of 1 can be hydrolyzed without effect on a ketal grouping. Another advantage is that the intramolecular Wittig-Homer reaction proceeds without isomerization of the initially formed cyclopentenone. 

Axial hydride delivery in the Luche reduction was employed as a key step in the total synthesis of (-)-mintlactone (16).18 Utilizing Luche conditions, (+)-pulegone (14) was reduced stereoselectively to give cri-pulegol (15) in 98% yield. Ozonolysis was followed by acylation and an intramolecular Wittig-Homer reaction to complete the short, efficient synthesis of the target molecule. 

Intramolecular Friedel-Crafts or Wittig-Homer reaction... 

Synthetic analogues have been prepared as exemplified in Scheme 14 [95]. A first Wittig-Homer olefination of aldehyde 107, followed by acidic treatment, generates cyclohexenone 108. Chemo- and stereoselective reduction of the latter with 9-BBN followed by sy -selective epoxidation of the allylic alcohol (lateral hydroxyl group control) by w-chloroperbenzoic acid gives 109. Selective tosylation of its secondary alcohol moiety (steric hindrance makes the tosylation of the tertiary alcoholic moiety difficult) and subsequent deprotonation of the tertiary alcohol with NaH provide an alcoholate that undergoes an intramolecular displacement reaction. 

---