Palladium catalysis allylation

The synthesis of thiepins 14 was unsuccessful in the case of R1 = i-Pr,79 but if the substituents in the ortho positions to sulfur arc /erf-butyl, then thiepin 14 (R1 = t-Bu R2 = Me) can be isolated in 99% yield.80 Rearrangement of diazo compound 13 (R1 = t-Bu R2 = H), which does not contain the methyl group in position 4, catalyzed by dimeric ( y3-allyl)chloropalladium gives, however, the corresponding e.w-methylene compound. The thiepin 14 (R1 = t-Bu, R2 = H) can be obtained in low yield (13 %) by treatment of the diazo compound with anhydrous hydrogen chloride in diethyl ether at — 20 C.13 In contrast, the ethyl thiepin-3,5-or -4,5-dicarboxylates can be prepared by the palladium catalysis method in satisfying yields.81... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

The molybdenum-catalyzed asymmetric reaction differs from the palladium-catalyzed reaction in several ways, the most important of which is the different regios-electivity achieved. Molybdenum-catalyzed reactions favor the most sterically hindered position (Eq. 11.39), in contrast with palladium catalysis. The molybdenum-catalyzed allylations also suffer from significantly lower reactivity. 

Allyl sulphones can be converted to dienes by alkylation and elimination of sulphinic acid under basic conditions (equation 64)105. Several vitamin A related polyenes have been synthesized following this two-step protocol (Table 10)106. The poor leaving-group ability of the arylsulphonyl group requires treatment with strong base for elimination. However, elimination of the allylsulphonyl group takes place readily under palladium catalysis (equation 65)107. Vinyl sulphones can be converted to dienes via Michael addition, alkylation with allyl halides and elimination of sulphinic acid sequence (equation 66)108. 

Platinum-catalyzed allylation of aldehydes with allyltin reagents was first reported in 1995.4S7 457b,483 483a Ar0matiC) aliphatic, a,/3-unsaturated aldehydes and even cyclohexanone undergo allylation with allyltributyltins in the presence of PtClgtPP 113)2 >n THF at room temperature or higher temperature (Equations (123) and (124)). Allylplatinum species are considered to be the active intermediates on the basis of related mechanistic studies on palladium catalysis. 

The group of allyl-based linkers was developed by Kunz et al. [49] Linkers of the general allyl type are particularly valuable, because they are removable under almost neutral conditions using palladium catalysis and are orthogonally stable towards the commonly used acid and base-labile protecting groups (Tab. 3.2). 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

Ellman used silyl chemistry for the direct linkage of aromatics onto the solid support by converting an aryl bromide to aryl lithium and reacting this with a silyl resin.90 It is the production of the silyl resin that is of interest in the context of this review, since an in situ Suzuki coupling was used to link the allyl silane to bromomethyl polystyrene resin (Scheme 40). 9-BBN is used to carry out the regioselective hydroboration, and this is linked to the resin with palladium catalysis in the usual way. After brief exposure of this... 

Alkylation and deprotection of N-protected aminomethylphosphonate esters 6 are shown in Scheme 6. The nitrogen is protected as the imine derived from benzophenone or a benz-aldehyde, and a variety of conditions are used for deprotonation and alkylation (Table 2). The benzaldehyde imine of aminomethylphosphonate can be deprotonated with LDA and alkylated with electrophilic halides (entries 1 and 2). For the best yields, saturated alkyl bromides require an equivalent of HMPA as an additive. 36 Allylic esters can be added to the carbanion with palladium catalysis (entries 3-7). 37,38 For large-scale production, phase-transfer catalysis appears to be effective and inexpensive (entries 8-12). 39,40 ... 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Several new leaving groups have been discovered recently which merit special discussion. Allyl sul-fones, surprisingly, function as substrates for palladium catalysis.86 As the sulfone group had previously been proven to be able to stabilize an adjacent carbanion, this result allowed allyl sulfones now to be considered as synthons for 1,1- and 1,3-dipoles (equation 10). That is, the allyl sulfone can be used alternately as a nucleophile and electrophile, greatly extending its synthetic utility. 

The copper-catalysed asymmetric conjugate addition of dialkylzinc leads to homo-chiral zinc enolates.28 These intermediates have been trapped in situ with activated allylic electrophiles, without the need for additional palladium catalysis (Scheme 3). 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

Palladium-catalyzed allylation reactions proceed with net retention of configuration that is the result of two inversions.118-120 132-135 Grignard reactions with nickel or copper catalysis proceed with net inversion.128 136-138... 

Direct allylation of rhodanine 49 (Scheme 13) under Pd(0)-catalysis with cinnamyl ethyl carbonate affords the /V-allylated compound 50. However, allylation with cinnamyl bromide and a base is not regioselective, producing a mixture of 50 and sulfide 51. Sulfide 51 isomerizes to 50 under palladium catalysis (N > S), thus indicating that Pd(0)-catalyzed allylation of 49 is thermodynamically controlled (93T1465). 

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