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    Home > ACS catalyst: PD catalyzed isocyanation of allyl phosphate

    ACS catalyst: PD catalyzed isocyanation of allyl phosphate

    • Last Update: 2019-05-07
    • Source: Internet
    • Author: User
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    Cyanide is a typical nucleophilic reagent with multiple reaction sites The compound can react with the electrophilic reagent to form C-terminal substituted cyanides or N-terminal substituted isocyanides (scheme1, eq.1) According to Kornblum rule, the above reactions should theoretically generate isonitriles, but most of them will generate nitriles with more stable kinetics and thermodynamics Up to now, the catalytic system for the nucleophilic addition of isonitriles is limited to scheme 1a and scheme 1b Based on the above research background, Takeshi ohkuma research team of Hokkaido University in Japan successfully reported the first case of PD (OAC) 2-catalyzed allylic isocyanation of allylic phosphate (scheme 2a) Relevant research results were published in acsacatal (DOI: 10.1021 / acscalal 9b00858) It is worth mentioning that Tsuji research group obtained allylic cyanide (scheme 2b) through the reaction of allylic ester with tmscn catalyzed by Pd (PPh3) 4 Due to the difference of Pd catalyst and leaving group, the selectivity of the two reactions is quite different (picture source: ACS catalyst.) firstly, the author optimized the reaction conditions with diethyl phenylpropenylphosphate as template substrate (Table 1) After the selection of catalyst and solvent, the author found that the target product can be obtained in 96% yield by reacting diethyl phenylpropenylphosphate with 2.0 equiv tmscn for 3 h in argon with 2 mol% PD (OAC) 2 as catalyst and toluene as solvent at 80 ° C It is worth noting that the yield of the reaction in air is equivalent to that in argon (picture source: ACS catalyst.) then, under the optimal reaction conditions, the author investigated the effect of leaving group on the reaction (Table 2) When the leaving group is ethyl, phenyl substituted phosphate and imine ester, the reaction conditions can be well adapted and the target product can be obtained with high yield If the dissociated group is trifluoroacetate, acetate, carbonate and bromide, the corresponding target product cannot be obtained (picture source: ACS catalyst.) under the optimal reaction conditions, the author also investigated the reactions of allylic phosphate in argon (black data) and air (red data) respectively (Table 3) All kinds of phenyl, thiophene, indole and cyclohexyl substituted allyl phosphate can adapt to the reaction conditions well, and the target product can be obtained with high yield and excellent E / Z ratio It is worth noting that β - methylphenylpropenyl phosphate and 5-phenyl-2-pentene phosphate are not highly resistant to the reaction conditions, the E / Z ratio of the product is relatively low, and the formation of branched products can be observed At the same time, under the optimal reaction conditions, the z-phenylpropenylphosphate will be converted into a 2:1 E / Z isonitrile mixture (scheme 3) (picture source: ACS catalyst.) in order to better clarify the reaction mechanism, the author further conducted a series of control experiments (scheme 4) PD (PPh3) 4 can catalyze the reaction of allyl ester and tmscn in THF solution, and the nitrile can be obtained in high yield Under the same conditions, the reaction of allyl phosphate with tmscn can yield isonitrile in medium yield This shows that the leaving group has a great influence on the regioselectivity of the reaction (scheme 4a) The reaction of η 3-phenylpropenyl-pd (II) and tmscn in toluene-d 8 solution was detected by hydrogen spectrum It was found that only scheme 4B was detected η 3-phenylpropenyl-pd (II) can react with silver phosphate to form π - allyl-pd (II) phosphate The phosphate can further react with tmscn to obtain a complex mixture, which contains a 3% yield of nitrile, but no isonitrile It is suggested that π - allyl PD (II) intermediate (scheme 4C) is not experienced in allylic isocyanation PD (CN) 2 (PPh3) 2 can be obtained by the reaction of PD (PPh3) 4 with tmscn of 5 equiv in 86% yield The PD (II) complex can be further used to catalyze the allylic isocyanate reaction to obtain isocyanate (scheme4d) (picture source: ACS catalyst.) next, the author examined the role of PD source in the reaction (scheme 5) PD (OAC) 2 can react with excessive tmscn in toluene to obtain PD (CN) 2 (eq.1) PD (CN) 2 can be used to catalyze allylidene isocyanate reaction Linear isocyanate 1a (yield 75%) and branched isocyanate 2A (yield 9%) are obtained The catalytic effect of PD (CN) 2 is not as good as that of PD (OAC) 2 (eq.2) The equivalent PD (CN) 2 did not react with allyl phosphate, indicating that PD (CN) 2, which was produced in situ by Pd (OAC) 2 and tmscn, could not be used as an active nucleophile (eq.3) Without PD source, TMS (OAC) can catalyze the reaction and obtain 1a and 2A in lower yield, which indicates that TMS cation of Lewis acid seems to participate in the activation process of allyl phosphate (Eq.4) Based on the results of control experiments, the author speculates on the possible mechanism (scheme 6) First, Pd (OAC) 2 can react with excess tmscn to obtain neutral PD (CN) 2 and acidic (TMS) [PD (CN) 3] and (TMS) 2 [PD (CN) 4] complexes Then, Pd (CN) 2 and TMS cation can be used as Lewis acid activated allylic phosphate, Pd (CN) 3] – and Pd (CN) 4] 2 – and tmscn can be used as N-terminal nucleophile to react with activated substrate to obtain allylidene isocyanide It is worth noting that in the presence of PD (CN) 2 and tmscn, a rearrangement reaction can take place in 2a, which is gradually converted into 1a Secondly, the E / Z ratio of the product depends on the thermodynamic properties Linear isonitriles contribute to the formation of Z-configuration products, while the rearrangement process of branched isonitriles is relatively slow, so branched isonitriles can be observed (picture source: ACS catalyst.) Summary: Takeshi ohkuma research team of Hokkaido University reported the first case of PD (OAC) 2-catalyzed allyl phosphate and tmscn allyl isonitrilic acid esterification, which can yield isonitriles in high yield At the same time, the author carried out a control experiment to further clarify the reaction mechanism.
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