Open in a separate window A new and general strategy for the synthesis of sequence-defined polymers is described that employs relay metathesis to promote the ring opening polymerization of unstrained macrocyclic structures. Biopolymers, such as proteins and DNA, clearly illustrate the power of defined polymer sequences, with remarkable functions such as catalysis, molecular recognition, and data storage emerging. Inspired by these natural, sequence-defined materials, strategies to control the primary structure of synthetic polymers have become an active area of research with the aim to develop materials with next-generation performance and functions.
However, the corresponding mono- or diallyl vinylphosphonate esters undergo facile cross metathesis reactions. The improved reactivity is attributed to a relay step in the cross metathesis reaction mechanism. As expected, the reactions generally proceed with complete chirality transfer.
Various carbon, nitrogen, and oxygen nucleophiles participate in the palladium-catalyzed substitution reactions of phosphono allylic carbonates 1. Palladium catalysed reaction of phosphono allylic carbonates. Natural products prepared using vinyl phosphonate intermediates.
Jump to Figure 1 The potential of vinylphosphonates as intermediates in organic synthesis is limited by their chemistry. Unlike the parent compound, vinylphosphonates substituted with an aryl or alkyl group on the alkene appear to have somewhat limited reactivity.
This lack of reactivity is exemplified by the Grubbs cross metathesis reaction . Grubbs and co-workers classified terminal vinylphosphonates as type III substrates .
Type III alkenes do not homodimerize, but will engage in alkene cross metathesis reactions. 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.
An alternative approach could involve an alkene cross metathesis reaction between the vinylphosphonate and a styrene 5 to 7. Approaches to the synthesis of centrolobine.
However, Hoye et al. Similarly, Hansen and Lee employed an allyl ether to activate enynes toward cross metathesis .
Furthermore, there are several examples of vinylphosphonates participating in ring closing metathesis RCM reactions . Therefore, given the propensity for vinylphosphonates to undergo RCM, it was proposed that an allyl phosphonate ester 14 would act as an initial site of metathesis, which would lead to a relay cross metathesis and thus render vinylphosphonates reactive.
Relay ring closing metathesis and relay cross metathesis. 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.
Cross metathesis reactions of vinyl phosphonates. A solution of the vinylphosphonate 12b, 1. 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.
The ratio of di- to mono-allyl phosphonate esters increases with the duration of reaction. Transesterification of phosphonate esters. 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 .Passing the baton: The relay ring-closing metathesis (RRCM) reaction of complex polyenes 1 has been studied.
Several relay subunits (T) were examined and many did not sufficiently activate the monstermanfilm.com allylmalonate-containing relay subunit solved this problem, and efficiently lead to the diene monstermanfilm.com=triisopropylsilyl. 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.
Total Synthesis of Peloruside A Through Kinetic Lactonization and Relay Ring-Closing Metathesis Cyclization Reactions Thomas R. Hoye, Junha Jeon, Lucas C. Kopel, Troy D. Ryba, Manomi A. Tennakoon, and Yini Wang. Angew. Chem.
Int. Relay Ring-Closing Metathesis and Total Synthesis of Oximidine III T. R. Hoye et al. JACS , , J. A. Porco et monstermanfilm.com , 43, Jun’s Current Literature , Relay Ring-Closing Metathesis (RRCM): A Strategy for Directing Metal Movement Throughout Olefin Metathesis Sequences Thomas R. Hoye *, Christopher S.
Jeffrey, Manomi A. Tennakoon, Jizhou Wang, and Hongyu Zhao. Relay Ring-Closing Metathesis (RRCM): A Strategy for Directing Metal Movement Throughout Olefin Metathesis Sequences Thomas R. Hoye *, Christopher S.
Jeffrey, Manomi A. Tennakoon, Jizhou Wang, and Hongyu Zhao.