Lactones with phosphoranes

There have been extensive studies on the reaction of dioxetanes and dioxetanones with nucleophiles (C, N, P, and S) and the reader is directed to CHEC-II(1996) for an exhaustive list up to 1996. The most common reactions of dioxetanes have been with phosphorus nucleophiles. The phosphines and phosphites first insert into the 0-0 bond. The phosphorane intermediate then collapses to afford phosphine oxide or the trialkylphosphate and the corresponding epoxide (Scheme 6). The same is true for the treatment of a-peroxy lactones with phosphines and phosphites except that the so-formed a-lactone intermediate undergoes decarboxylation and ultimately furnishes a ketone <1997JOC1623>. 

In the meantime, the Wittig olefination of carbohydrate lactones with stabilized phosphoranes at high temperature was discovered. This was an efficient reaction which worked with y- and 5- lactones in excellent yields. This way another new class of exo-glycals 3 was available, as Z/E mixtures but with an interesting push-pull substitution of the double bond (Scheme 1). ... 

Several papers have been devoted to the subject of reactions of phosphoranes with carboxylic acids and their derivatives. Thus triphenylphosphine dibromide (111) in acetonitrile cleaves lactones,93 while the corresponding dichloride (112) converts esters into acid chlorides.94 The reactions of esters with phosphorus pentachloride (101) have been studied further,95 and the influence of structural changes on the yields of products (113) and (114) has resulted in minor modifications to the mechanism previously96 outlined. 

Hydroxybenzofuran-5-carbaldehydes 682 can react with carbethoxymethylenetriphenyl-phosphorane 683 to afford biologically active furanocoumarins 684 in high yield. The reaction proceeds via Wittig reaction of the phosphorane 683 with the aromatic aldehyde to form the intermediate cinnamate, which then undergoes isomerization of the double bond and lactonization to furnish the desired furanocoumarins 684 (Scheme 165) <1995T3087>. 

Treatment of the ot/ o-quinones 687 with 2equiv of carbethoxymethylenetriphenylphosphorane 688 affords coumarins in good yield. The reaction proceeds via Wittig olefination of the C-6 carbonyl to form the intermediate ort o-quinone methanides 689. Michael addition of a second equivalent of the phosphorane 688 followed by a Hoffmann type elimination of triphenylphosphine affords the intermediate 690. Intramolecular lactonization then forms the desired coumarins (Scheme 167) <2002J(P1)1455>. 

Higher yields (43 %) of (52), together with some cis-isomer (53), were obtained by use of 21-iodopregnenolone acetate and methoxycarbonylmethylenetriphenyl-phosphorane. Sodium borohydride reduction of (54) or (55) gave (56), and not the expected substituted lactone. Similarly, the 5a-analogue of (54) gave (57)... 

Yields of largely (E)-isomers are usually above 70% and the method works equally well with lactones to give -hydroxy unsaturated esters. Both phosphoranes and phosphonates derived from long-chain... 

Phosphoranes failed even in refluxing toluene to undergo Wittig olefination of lactones, unlike other carbonyl compounds. However, under MWI for 90 s, lactone 102 reacted with ethoxycarbonyl methylidene triphenyl phosphorane on mixing a 1 1.2 ratio to give 104 and 105. Similarly, 103 gave 106 and 107 after MWI for 110 s, each as a mixture of isomers in 80-82% yields. The EjZ product ratio was 20/80 for 104 and 105 and 15/85 for 106 and 107 (Scheme 21) (99TL165). 

Reaction with Stabilized Phosphoranes. lodo enol lactones are obtained from reaction of the corresponding (w-carboxy keto phosphoranes with NIS (eq 21). ... 

The diazo-ketone (43) forms the j -lactone (44) and 2-methylhexan-3,5-dione on refluxing in benzene, presumably through alkyl migration and cyclization of resulting hydroxyketen. Malonyl anhydrides (46) and ketens are formed from the deoxygenation of malonyl peroxides with triphenyl-phosphine, possibly via an intermediate phosphorane (45). 

Halogenation at C-2. As above described monobromo exo-glycals are suitable substrates for palladium catalysed cross-coupling reactions. The direct reaction of monobrominated phosphoranes with lactones is not straightforward. However, the facile addition of chlorine to dichloroolefins 1 has been described some years ago. Thus halogenation of anomeric double seemed a viable process and bromi-nation of compounds 3 was examined. Considerable experimentation led to find the proper conditions which allowed the formation of brominated eoco-glycals from 3 (Scheme 5). 

The pivalate was reductively removed at C25 using lithium triethylborohy-dride. It is notable that the lactone was not disturbed, perhaps an indication of the aforementioned steric congestion. Oxidation of the primary alcohol then gave aldehyde 36. A Wittig reaction with the phosphorane derived from 37 gave the Z-olefin and removal of the C9 protecting group completed the synthesis of lasonolide-A (1). 

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