Approaches to the synthesis of centrolobine. Jump to Scheme 12 Analysis of the TBAI allylation mechanism suggested that a good approach to mono-allyl phosphonate 14a would be a stoichiometric demethylation followed by a rapid allylation under ambient conditions.
In general, reaction of either mono- allyl or diallyl vinylphosphonates with methyl acrylate proceeded with comparable yields.
Similarly, reaction of vinylphosphonate 21a with 4-fluorostyrene and 4-benzyloxystyrene gave the tetrahydropyrans 26 and 7, respectively. The ratio of di- to mono-allyl phosphonate esters increases with the duration of reaction.
The formation of the dimeric product 27 is probably the result of a competitive cross metathesis reaction between the tetrahydropyran 25 and the metal alkylidene 34 . A selective synthesis of mono-allyl phosphonates.
Ring closing vs relay cross metathesis. However, if a relay-arm is judiciously introduced, the dihydrofuran is obtained as the sole product. Jump to Scheme 13 Conclusion The experiments presented above have demonstrated that whereas the dimethyl esters of substituted vinylphosphonates are characterized as type IV substrates in alkene cross metathesis reactions and are unreactive, the corresponding allyl esters show significantly improved reactivity.
However, a few tricks have been developed to tame some of these recalcitrant substrates. However, the corresponding mono- or diallyl vinylphosphonate esters undergo facile cross metathesis reactions.
In the previous cases, the relay strategy helped circumvent the lack of reactivity of hindered olefins, but it can also be useful in differentiating between olefins and competitive metathesis pathways.
Unlike the parent compound, vinylphosphonates substituted with an aryl or alkyl group on the alkene appear to have somewhat limited reactivity. More highly substituted vinylphosphonates 5 and 19 failed to react at all with methyl acrylate under similar conditions, even with higher catalyst loading and extended reaction times.
The reaction progress was monitored by 31P NMR spectroscopy. Palladium catalysed reaction of phosphono allylic carbonates. As expected, the reactions generally proceed with complete chirality transfer. So, by introducing a relay-arm, and providing an easy-to-load-on olefin A, the ruthenium can be delivered to olefin B via RRCM releasing the substituted cyclopenteneand then cyclize onto olefin C, yielding the desired tetrasubstituted cyclic olefin.
Similarly, diallyl phosphonate 21b was reacted with methyl acrylate to give the corresponding unsaturated ester 24 in good yield along with the phosphonate heterocycle Jump to Figure 1 The potential of vinylphosphonates as intermediates in organic synthesis is limited by their chemistry.
The metal alkylidene then reacts with the vinylphosphonate in a ring closing metathesis RCM to generate the oxaphosphole 22 and a new metal alkylidene The major weakness of this approach is that the mono-allyl phosphonate can further react with iodide leading ultimately to the diallyl phosphonate 14b.
In addition, the 31P NMR spectrum of the crude reaction mixture indicated the formation of a new phosphorus-containing product with a signal at 43 ppm, consistent with formation of the oxaphosphole 22 . The improved reactivity is attributed to relay step in the cross metathesis reaction mechanism.
It was proposed that E diallyl vinylphosphonates would prefer to form the 5-membered ring oxaphosphole 30 and therefore, like the corresponding mono-allyl phosphonates, should engage in relay cross metathesis reactions. During the synthesis of phosphonate based ionic liquids, Sachnov et al.
Supporting Information Supporting Information File 1: Furthermore, there are several examples of vinylphosphonates participating in ring closing metathesis RCM reactions .
Jump to Scheme 11 Once the activation of vinylphosphonates toward cross metathesis was established, it became clear that the overall success of this method would depend on a selective, high yielding synthesis of mono-allyl phosphonates.
This lack of reactivity is exemplified by the Grubbs cross metathesis reaction . Since alkene cross metathesis is a powerful method of combing organic fragments in natural product synthesis, the value of vinylphosphonates as synthetic intermediates would increase if their reactivity could be enhanced to a level where they would participate in cross metathesis reactions.
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. A proposed mechanism for the TBAI catalysed transesterification. Various carbon, nitrogen, and oxygen nucleophiles participate in the palladium-catalyzed substitution reactions of phosphono allylic carbonates 1.
The improved reactivity is attributed to a relay step in the cross metathesis reaction mechanism. However, attempts to force the reaction with longer reaction times, increased TBAI, or increased ally bromide, leads to an increase in diallyl phosphonate 14b.Ring-ClosingMetathesis** XiangWang,EmmaJeanBowman,mi-centre.com, mi-centre.com,Jr.* Vacuolar-type initiation of the metathesis reaction.
We hoped that the rutheniumcatalyst10(Scheme2)wouldreactwiththeepoxy of a relay moiety. We hoped that the ruthenium catalyst. Scheme 3: Relay ring closing metathesis and relay cross metathesis. Jump to Scheme 3. Results and Discussion.
A series of cross metathesis reactions were performed to establish the baseline reactivity of vinylphosphonates. Not surprisingly, the. Relay Ring-Closing Metathesis (RRCM): A Strategy for Directing Metal Movement Throughout Olefin Metathesis Sequences.
Ring Closing Metathesis (RCM) The Ring-Closing Metathesis (RCM) allows synthesis of 5- up to membered cyclic alkenes. The E/Z-selectivity depends on the ring strain.
The Ru-catalysts used tolerate a variety of functional groups, but normally the molecule must have polar side chains that are able to build a template for the catalyst. Examples of how Relay Ring Closing Metathesis (RRCM) can be used to tame recalcitrant substrates. The other side: A convergent total synthesis of peloruside A (1) is described.
The key strategic features are a diastereoselective lactonization to generate a C5–C9 valerolactone from the C 2 -symmetric ketone 3, and a relay ring-closing metathesis reaction to produce a dehydrovalerolactone 2.Download