Cinnamyl derivative

The enantioselective carbolithiation of cinnamyl derivatives described by the group of I. Marek and J.F. Normand [2] is one of the few reports on the use of sparteine as a catalytic activator of organoUthium carbanions... 

For acyclic allylic substrates the situation is more complex, since a larger number of reactive conformations, and hence corresponding transition states, compete. Thus, methyl cinnamyl derivatives 163 (X = OAc), upon treatment with lithium dimethylcuprate, mainly gave the Sn2 substitution product 166 (entry 1, Tab. 6.6 and Scheme 6.34) [80]. The preference for the Sn2 product is expected, since deconjugation of the alkene system is electronically unfavorable. 

Since carbohthiations usually proceed as syn additions, 458 is expected to be formed first. Due to the configurationally labile benzylic centre it epimerizes to the trani-substitu-ted chelate complex epi-45S. The substitution of epi-458 is assumed to occur with inversion at the benzylic centre. Sterically more demanding reagents (t-BuLi) or the well-stabilized benzyllithium do not add. The reaction works with the same efficiency when other complexing cinnamyl derivatives, such as ethers and primary, secondary, or tertiary amines, are used as substrates . A substoichiometric amount (5 mol%) of (—)-sparteine (11) serves equally well. The appropriate (Z)-cinnamyl derivatives give rise to ewf-459, since the opposite enantiotopic face of the double bond is attacked . 

ZO099 Kurokawa, M., C. A. Kumeda, ]. Ya-mamura, T. Kamiyama, and K. Shiraki. Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice. Eur J Pharmacol 1998 348(1) 45-51. 

J. F. Normant, J. F. Enantioselective carbome- 484 talation of cinnamyl derivatives new access to chiral disubstituted cyclopropanes. Configurational stability of benzylic organozinc halides. Chem. Eur. J. 1999, 5, 2055-2068. 485... 

Allyl ethers of orf/io-disubstituted phenols rearrange to the corresponding p-allylphenols. It is noteworthy that the para rearrangement is not usually accompanied by inversion of the allyl group.8-4-6-6-7 For example, cinnamyl 2-carbomethoxy-6-methylphenyl ether (III) rearranges without inversion8 to yield the p-cinnamyl derivative (IV). 

The Pd(0)-catalyzed allylations of 120, benzothiazolethione 123, and benz-imidazolethione 125 (Scheme 26) have been studied by the current authors (93T1465). In all cases, the sulfides 121 (R = Ph), 124, and 126 were formed, either as major or as exclusive products. Attempts to isomerize sulfides into A-cinnamyl derivatives were made. Slow conversions were observed for sulfides 121 (R = Ph) and 124 under forcing conditions, thus indicating that sulfides are the products of kinetic control and the /V-cinnamyl derivatives are the products of the thermodynamic control (N > S), which is not easily attainable. Of course, the reaction of 125 with two equivalents of allylating agent gives the S./V-dicinnamyl derivative 127. 

Abnormal olefin arylation reactions which are of interest mechanistically and preparatively occur with some allylically substituted compounds. The ailylic esters and ethers appear normal and produce cinnamyl derivatives exclusively while ailylic alcohols and chlorides are abnormal. Ailylic alcohols and "arylpalladium acetates form 3-arylaldehydes from primary ailylic alcohols and 3-arylketones from secondary alcohols 3°). The mechanism of reaction apparently involves anti-Markovnikov addition of the palladium compound to the double bond followed by elimination of the hydrogen atom on the hydroxyl-bearing carbon rather than the benzylic hydrogen. This again would be elimination of the more electronegative hydrogen atom. 

Scheme 2 Enantioselective hydrogenation a-(acetylamino)cinnamyl derivatives...

Another illustration of the role of the conformational mobility on the levels of the observed asymmetric induction is shown by the intramolecular photon cycloaddition of cinnamyl derivatives of vinyl glycine 73 into a mixture of 74 and 75 (Scheme 17). In the sensitized reaction and for steric reasons, the attack of excited styrene on the vinyl oxazolidinone 76 gives mainly 77 [55]. 

It is well known that copper salts can catalyze the photocycloaddition of dienes [56]. The reaction can be very diastereoselective and useful as an access to polycyclic molecules, especially 1 - vinyl-2-allylcyclanes [57]. The reaction of vinylglycine, cinnamyl derivatives 76, and analogs is also catalyzed by Cu(I) produced in situ by the reduction of cupric triflate. The coordination of the double bonds to the copper ion during the [2 4- 2]-photocycloaddition process increase ... 

Stereoselective oxidative dimerization of cinnamyl derivatives bearing an Oppolzer sultam as chiral auxiliary has been performed both enzymatically (HRP/H2O2) and by chemical means with Ag20. This method provides an enantioselective access to dehydrodiconiferyl ferulate (Equation 148) <2001T371>. 

Treatment of CHa=CHCHaMn(CO)5, MeCH=CHCHaMn(CO)5, MeaC=CHCHaMn(CO)5, CH2=C(Cl)CHaMn(CO)5, and PhCH= CHCHaMn(CO)B with sulfur dioxide affords the corresponding S-sulflnates (64, 67). The 2-butenyl and 3-methyl-2-butenyl complexes react with rearrangement, whereas the cinnamyl derivative affords the correspondingunrearrangedallylsulfinate. Surprisingly, C1CH=CHCH2-Mn(CO)s yields Mn(CO)5Cl and an unidentified oil when treated with either neat SOa or SOg in pentane (67). 

The addition of alkyllithiums to allylic alcohols, originally described by Felkin and Crandall [83], has recently acquired new interest due to the enantioselective approach of the carbometallation reaction of cinnamyl derivatives. Indeed, asymmetric carbolithiation of ( )-cinnamyI alcohol in hexane or cumene, in the presence of the readily available chiral diamine (—)sparteine, leads to the carbometallated product in 82% ee. Primary as well as secondary alkyllithiums lead to identical enantioselection [128] (Scheme 7-108). 

Since cinnamyl derivatives were shown to be unreactive towards the addition of RLi in cumene at 0°C without external diamine, the potential for catalysis was obvious. The results show that addition of these derivatives to n-BuLi and a catalytic amount, of (—)-sparteine (5%) also leads to a good enantiomeric excess [128], even on a large scale [129]. (Scheme 7-110). 

Adams TB, Doull J, Feron VJ, et al. (2002) The FEMA GRAS assessment of cinnamyl derivatives used as flavor ingredients. Food and Chemical Toxicology 40 429-451. 

The reaction of lithiated carbanions of l-(trimethylsilyl)cinnamyl-, prenyl-, and crotylphosphonates with aldehydes has been studied. The cinnamyl derivative undergoes a Peterson reaction with aromatic or aliphatic aldehydes to give the phosphonodienes in high yields and high stereoselectivity. Thus,... 

An attempt to effect palladium catalysed C-allylation of 3,5-dimethyl-2/f-1,2,6-thiadiazine 1,1-dioxide (137) is only moderately successful, as allylation at C-4 to give the cinnamyl-derivative (138 13% yield) is accompanied by equal amounts of the A-cinnamyl derivative (139) (Equation (12))... 

Cinnamyl-Z-ecgonine has been obtained by acylation of Z-ecgonine with cinnamic anhydride. Esterification of this cinnamyl-derivative with methanol gave cinnamylcocaine (103). After the physical properties of cinnamylcocaine had been established it was subsequently isolated from Java coca leaves (109) and from Erythroxylum monogynum Roxb. (77). It has been reported (77) that cinnamylcocaine is devoid of mydriatic and anaesthetic properties. 

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