Metathesis And Substitution

Metathesis And Substitution-39
The ratio of di- to mono-allyl phosphonate esters increases with the duration of reaction.A subsequent reaction of vinylphosphonate 12b employing 5 equivalents of allyl bromide, 5 mol % TBAI and 18 hours at reflux resulted in 87% conversion with 1.2:1 ratio of mono- to diallyl ester (14a and 14b).

Grubbs and co-workers classified terminal vinylphosphonates as type III substrates [11].

Type III alkenes do not homodimerize, but will engage in alkene cross metathesis reactions.

Carbonyls and alkenes, two of the most common functional groups in organic chemistry, generally do not react with one another.

Now, a simple Lewis acid has been shown to catalyse metathesis between alkenes and ketones in a new carbonyl olefination reaction.

A solution of the vinylphosphonate 12b, 1.1 equivalents of allyl bromide and 5 mol % TBAI in toluene was heated at reflux for 7 hours to give a 53% conversion to both the mono- and diallyl vinylphosphonates 14a and 14b in a 10:1 ratio.

The overall conversion could be improved with excess allyl bromide, increasing the amount of TBAI and prolonged heating times, either at reflux or in a microwave reactor.An alternative approach could involve an alkene cross metathesis reaction between the vinylphosphonate and a styrene (5 to 7).Since substituted vinylphosphonates are reluctant to participate in cross metathesis reactions (Scheme 3), this approach to the synthesis of cetrolobine appeared to have little merit. reported the concept of “relay ring closing metathesis (RRCM)”, wherein typically unreactive α,ω-dienes bearing 1,1-disubstituted ethylene moieties 9 would react via the intermediacy of an additional terminal alkene 11 (Scheme 3) [19-21].Similarly, Hansen and Lee employed an allyl ether to activate enynes toward cross metathesis [22].Furthermore, there are several examples of vinylphosphonates participating in ring closing metathesis (RCM) reactions [23-25].The reaction proceeded to 96% conversion and gave 1:1.8 ratio of mono- and diallyl vinylphosphonates 21a and 21b.The products were isolated by silica gel chromatography to give 27% yield of the mono-allyl and 36% yield of the diallyl phosphonate esters.Vinylphosphonates formed in this way, for example 2a–e (Figure 1), have been used in the synthesis of the natural products turmerone [4] and enterolactone [5], the phosphonate derivatives of the natural product cyclophostin [6], the C18–C34 fragment of amphidinolide C [7], and the oxylipids from Australian brown algae [8].The potential of vinylphosphonates as intermediates in organic synthesis is limited by their chemistry.In particular, carbonate derivatives 1 (phosphono allylic carbonates) of allylic hydroxy phosphonates undergo palladium-catalyzed addition of nucleophiles to give γ-substituted vinylphosphonates 2 in high yield (Scheme 1).The nucleophile adds exclusively to the 3-position, with migration of the double bond into “conjugation” with phosphoryl group.


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