Allenyl/propargyl-substituted

Metal-mediated carbonyl allylation, allenylation, and propargylation of optically pure azetidine-2,3-diones were investigated in aqueous environments.208 Different metal promoters showed varied regioselec-tivities on the product formation during allenylation/propargylation reactions of the kcto-fi-lactams. The stereochemistry of the new C3-substituted C3-hydroxy quaternary center was controlled by placing a chiral substituent at C4. The process led to a convenient entry to densely functionalized hydroxy-ji-lactams (Eq. 8.82). 

This displacement of an allylic QH5Se group by a (CH,)3Sn group is observed also with allenyl, propargyl, and benzyl selenides, and in all cases results in the less substituted of the two possible trimethylstannyl compounds. 

Propargyltrimethylsilanes give allenyl derivatives on reaction with -acyliminium precursors. - On the other hand, application of allenyl-silanes or -stannanes provides access to propargyl-substituted lactams. All reactions proceed with high regio- and stereo-selectivity (equations 54 and 55). 4-Allenyl-azetidinones can be cyclized to A -carbapenem systems, mediated by Ag or Pd salts. - The reactions of ethoxylactams with allenylsilanes can be modified in such a way that bicyclic systems are obtained in one step (equation 56). ... 

The reactions with tertiary amines or phosphines that have no active hydrogen atoms result in platinacyclobutene cations, a rare species for late transition metal (Scheme 39). Substituted carbanions are added to the jj -allenyl/propargyl platinum complex to yield the neutral substituted-jj -TMM derivatives that undergo further [3 + 2] cycloaddition with good TT-acids as TCNE or maleic anhydride to produce highly substituted cyclopentanoids (Schemes 40, 41). 

Ovaska and Kyne (2008) have reported that a series of l-allenyl-2-propargyl substituted cyclopentanol derivatives undergo facile intramolecular microwave-assisted [2+2] cycloaddition affording strained tricyclic 5-6-4 ring systems (70-90% yield), as present in the natural product (-) sterpurene. Surprisingly, only those al-lenic systems were found to be reactive, which bear the allenyl and propargylic moiety in a trans relationship. 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

Tnfluoromethyl-substUuted 1,3-dipoles of the propargyl-allenyl type and trifluoromethyl-substituted nitrilium betaines. Tnfluoromethyl- [164, 765] and bis(trifluoromethy])-substituted [166, 167] nitrile ylides have been generated by different methods and trapped with various dipolarophiles to yield [3+2] [768] and [3+1] cycloadducts [769], respectively... 

The equilibrium between propargyl- and allenyl-tin compounds is not spontaneous, but it occurs in the presence of Lewis acids or coordinating solvents, and an ion-pair mechanism has been proposed (159). Substitution by iodine, or addition to chloral, occurs with propargyl/al-lenyl rearrangement (160, 161), analogous to the allylic rearrangement already mentioned. 

Friedel-Crafts reaction remains unexplored, possibly due to the difficulty of the cycloalkyne formation. A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3-6H20-catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols (Scheme 8) [24, 25]. FeCls, InCls, and Yb(OTf)3 also exhibit good catalytic activity for the reaction. 

Solvolysis of the propargyl chlorides E- and Z-24 (stereochemistry based on Cl and Ph25) in 80% aqueous ethanol at 50 °C gave, besides the corresponding solvent captured substituted propargyl products, the allenyl chlorides E- and Z-25 formed with complete retention via the allenyl cation intermediate (equation 6)25. 

Substituted allenyl cations 47 have been generated from propargyl alcohols 48 under stable carbocation conditions (Sbf s/f SOsII in SO2CIF) (equation 17). On the basis of 13C-NMR chemical shifts, the positive charge has been found to be extensively delocalized with the mesomeric allenyl cations contributing highly to the total ion structure36,37. 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

Substituted propargylic alcohols were found to undergo direct carbonylation to the corresponding butenolides in 67-98% yield (Eq. 9.120) [86]. This reaction requires a catalytic amount of Pd2(dba)3-CHC13 (4%) and l,4-bis(diphenylphosphi-no)butane (8%) in CH2C12 under an atmosphere of CO (600 psi) and H2 (200 psi) at 95 °C for 36 h. The cyclocarbonylation reaction is believed to proceed via an allenyl-palladium intermediate, which is formed by initial insertion of Pd(0) into the C-O bond of the alkynol followed by rearrangement (Scheme 9.25). 

Although the preparation of the substituted allene ether substrates for the Nazarov reaction is not the topic of this chapter, it is necessary to mention a few aspects of their synthesis. Lithioallene 1 (Eq. 13.13) can be trapped with chlorotri-methylsilane to give 35 [6]. Exposure of 35 to sec- or tert-butyllithium leads to allenyl-lithium 36, which can be trapped with alkyl halides or other electrophiles to give 37. Desilylation of 37 leads to 38. This is somewhat laborious, but it leads to allene 38 uncontaminated by propargyl ether 39. Exposure of 39 to n-butyllithium, followed by quenching with acid, typically produces mixtures of 38 and 39 that are difficult to separate. Fortunately, one need not prepare allenes 38 in order to access the C6-sub-... 

The ratios of nucleophilic substitution versus [3,3]-sigmatropic rearrangement for the collapse of allenyl(aryl)iodine(III), generated from the reaction of aryliodanes with propargylsilanes in the presence of Bp3.0Et2 in alcohols, have been determined. The mechanism proposed by the authors ° involves the generation of propargyl cations from the allenyliodine (III) via a unimolecular pathway. 

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