Amides homoallylic

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Ruthenium complexes containing this ligand are able to reduce a variety of double bonds with e.e. above 95%. In order to achieve high enantioselectivity, the reactant must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a functional group that can coordinate with the metal. The ruthenium-BINAP catalyst has been used successfully with unsaturated amides,23 allylic and homoallylic alcohols,24 and unsaturated carboxylic acids.25... 

An enantioselective imino-ene reaction was developed by Lectka to provide ct-amino acid derivatives.27 Aryl alkenes (cr-methyl styrene, tetralene), aliphatic alkenes (methylene cyclohexane), and heteroatom-containing enes, all gave high yields and high ee s of the homoallylic amides (Equation (17)). The mechanism of this reaction has been proposed to proceed through a concerted pathway. This mechanism is evidenced by a large kinetic isotope effect observed in the transfer of H(D). 

Ytterbium triflate [Yb(OTf)3] combined with TMSG1 or TMSOTf are excellent reagents for the conversion of a-methyl styrene and tosyl-imines into homoallylic amides 32 (Equation (19)) (TMS = trimethylsilyl).29 These conditions produce the first examples of intermolecular imino-ene reactions with less reactive imines. Typically, glyoxalate imines are necessary. A comprehensive examination of the lanthanoid metal triflates was done and the activity was shown to directly correlate with the oxophilicity scale. The first report used preformed imines, and subsequently it was found that a three-component coupling reaction could be effected, bypassing the isolation of the intermediate imine.30 Particularly noteworthy was the successful participation of aliphatic aldehydes to yield homoallylic amines. 

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

A recent study has indicated that the skeletal rearrangement step in the B12-catalysed isomerization of methylmalonyl-CoA to succinyl-CoA occurs not by a radical pathway but by an anionic or organocobalt pathway. A computational study of the isomerization of allyl alcohol into homoallyl alcohol by lithium amide has pointed to a process proceeding via a transition state in which the proton is half transferred between carbon and nitrogen in a hetero-dimer. l,l-Dilithio-2,2-diphenylethene... 

Ham et al. [60] used an unselective attack of a vinyl Grignard reagent on the iST-benzoyl-protected phenylalaninal 92 to generate alcohols 93 (Scheme 25). A tmns-selective, Pd(0)-catalyzed oxazoline formation starting from the homoallylic amide 93 was subsequently employed to build up the (S)-configuration at carbon atom C-3 of oxazoline 94. 

Reaction of the chiral lithium enolate of meso-2,6-dimethylcyclohexanone (6), generated by deprotonation with (R)-l-phenylethylamine and (/ )-camphor/(R)-l-phenylethylaniine derived chiral lithium amides (Table 1, entries 17 and 64) with 3-bromopropene, leads to homoallyl ketones of opposite absolute configuration in acceptable yield with poor to modest enantiomeric excess14, which can be determined directly by H-NMR spectroscopy in the presence of tris [3-(heptafluorohydroxymethylene)-D-camphorato]europium(III) [Eu(hfc)3]. 

Aryl homoallyl ketones and 4-methoxy phenyl ethers are also good substrates for the AD [8], whereas the structurally related allyl amides and thioesters give products with insufficient enantioselectivity. Homoallylic 4-methoxy benzoates perform relatively poor, which is consistent with Corey s proposed mechanistic model [9],... 

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

Some examples of photolytic intramolecular [2 + 2] cycloadditions which lead to the formation of lactones and lactams are sketched in Scheme 9.9. The allyl ester and N-monosubstituted amide do not undergo cydization, probably because of the high energy of the required E conformers. Cydization of the homoallyl ester does,... 

The basic Markovnikov selectivity pattern is partially or fully overrun in the presence of neighboring coordinating groups within the olefin substrate (Section 2.2.2). Known functionalities where inversed selectivity can occur include 3-alke-noylamides (e.g. 17 reacts to give a mixture of 18 and 19, Table 3) [43], homoallyl esters and alcohols, allyl ethers (but not necessarily allyl alcohols) [44], allyl amines, allyl amides, or carbamates (cf. 20 to 21) [45], allyl sulfides [46] or 1,5-dienes [47]. As a matter of fact, aldehyde by-products are quite normal in Wacker reactions, but tend to be overlooked. 

Although allylic lithiation by deprotonation of non-heterosubstituted compounds is possible using superbases (see section 2.6), in most cases allylic lithiation requires a directing heteroatom. (Non-heterosubstituted allyllithiums are best produced by reductive lithiation of allyl ethers or allyl sulfides - see section 4.4.) One of the few cases where this heteroatom is not a to the new organolithium is shown below the p-lithiation of a homoallylic amide 137. The reaction is particularly remarkable because of the possibility of competing deprotonation... 

The lithium derivative of the chiral chelating diamine (3 )-2-(l-pyrrolidinylmethyl)-pyrrolidine (6) has been used extensively in stereoselective synthesis, i.e. in the deprotonation of ketones and rearrangement of epoxides to homoallylic alcohols. The lithium amide has been crystallized from toluene solution, and X-ray analysis revealed that it forms a ladder-type tetramer with the two pyrrolidine nitrogens solvating the two lithiums at the end of the ladder38, (Li-6)4. 

The acyl moiety of capsaicin contains only one functional group, a double bond that is redundant for activity. On the contrary, the presence of the double bond is critical for the activity of olvanil, and interesting structure-activity relationships were discovered for this compound. Thus, an analog hydroxylated on the homoallylic carbon is easily available from the amidation of commercial and cheap ricinoleic... 

The stereoselectivities of the epoxidations of the homoallylic alcohols (104) and (105) and their benzoates (106) and (107) have been studied. The amide-directed epoxidation of the c/s-disubstituted al-kene (108) is stereoselective (equation 37). ... 

Oxazolidines and 1,3-Oxazinanes by Cyclization of O-Allylic and O-Homoallylic Amidals... 

The mercury-induced cyclization of amidals derived from secondary homoallylic alcohols afforded only six-membered ring products 7 via a 6-exo mode. For short periods (under kinetic control) the fa-isomer was the major product, while for longer periods (under thermodynamic control) the trans-isomer was formed with very high stereoselectivity161,162. 

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