A-allylic alkylation

Direct catalytic intermolecular a-allylic alkylation of aldehydes and cyclic ketones has been achieved using a one-pot combination of a transition metal catalyst, Pd(PPh3)4, and an organocatalyst a secondary amine which facilitates enamine catalysis.300... 

A simple method for the direct catalytic allylic alkylation of aldehydes and cyclic ketones has been developed.26 The direct catalytic highly chemo- and regio-selective intermolecular a-allyhc alkylation reaction has been mediated by an unprecedented combination of palladium and enamine catalysis which furnishes a-allylic alkylated aldehydes and cyclic ketones in high yield. 

Palladium-catalysed asymmetric a-allyl alkylation of acyclic ketones has been reported allyl enol carbonates of a wide range of ketones undergo allyl transfer in high yields and ees at room temperature.197... 

The three principal palladium-mediated reactions of interest in the synthesis of vitamin h(l) and carotenoids are (a) allylic alkylation of 7C-allylpalladium complexes, (b) Heck-type couplings, and (c) cross-coupling of alkenyl and alkynyl metal derivatives. 

Chen et al. developed the first asymmetric and chemoselective A-allylic alkylation of indoles with MBH carbonates. This method was realized by employing modified cinchona alkaloids (DHQD)2PHAL as organocatalysts. Either electron-rich or electron-deficient indoles could be employed and moderate to excellent enantioselectivity was achieved (62-93% ee) (Scheme 3.115). ... 

Scheme 4 Catalytic intermolecular a-allylic alkylation of cyclohexanraie...

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

In addition to the applications reported in detail above, a number of other transition metal-catalyzed reactions in ionic liquids have been carried out with some success in recent years, illustrating the broad versatility of the methodology. Butadiene telomerization [34], olefin metathesis [110], carbonylation [111], allylic alkylation [112] and substitution [113], and Trost-Tsuji-coupling [114] are other examples of high value for synthetic chemists. 

There are three sorts of C-H bonds in cyclohexene, and Table 5.3 gives an estimate of their relative strengths. Although a typical secondary alkyl C-H bond has a strength of about 400 kj/mol (96 kcal/mol) and a typical vinylic C-H bond has a strength of 445 kj/mol (106 kcal/mol), ail allylic C-H bond has a strength of only about 360 kj/mol (87 kcal/mol). An allylic radical is therefore more stable than a typical alkyl radical with the same substitution by about 40 kj/mol (9 kcal/mol). 

Because of resonance stabilization, a primary allylic or benzylic carbocation is about as stable as a secondary alkyl carbocation and a secondary allylic or benzylic carbocation is about as stable as a tertiary alkyl carbocation. This stability order of carbocations is the same as the order of S l reactivity for alkyl halides and tosylates. 

Problem 16.20 Refer to Table 5.3 on page 156 for a quantitative idea of the stability of a benzyl radical. How much more stable (in kj/mol) is the benzyl radical than a primary alkyl radical How does a benzyl radical compare in stability to an allyl radical ... 

Removal of the unsaturated side-chain appendage from C-8 in 22 provides diol lactone 23 and allylic bromide 24 as potential precursors. In the synthetic direction, a diastereoselective alkylation of a hydroxyl-protected lactone enolate derived from 23 with allylic bromide 24 could accomplish the assembly of 22, an intermediate that possesses all of the carbon atoms of PGF2o- It was anticipated that preexisting asymmetry in the lactone enolate would induce the... 

Additions of carbon nucleophiles to vinylepoxides are well documented and can be accomplished by several different techniques. Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pKa 10-20) proceeds under neutral conditions and with excellent regioselectivities [103, 104]. The sul-fone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh3)4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115, 116]. 

One contributing factor, which seems to have been largely ignored, is that the ring closed radical (in many cases a primary alkyl radical) is likely to be much more reactive towards double bonds than the allyl radical propagating species. This species will also have a different propensity for degradative chain transfer (a particular problem with allylamines and related monomers - see 6.2.6.4) and other processes which complicate polymerizations of the monoencs. 

Diallyl monomers find significant use in cyclopolymerization (Section 4.4.1). Transfer to monomer is of greater importance in polymerizations of allyl than it is in diallyl monomers.184 This might, in part, reflect differences in the nature of the propagating species [e.g. a secondary alkyl (115) v.v a primary alkyl radical (116)]. Electronic factors may also play a role,185... 

Das aus dem (a-Halogen-alkyl)-cyclopropan-System mit Organo-zinnhydriden gebildete Radikal kann sich zum entsprechenden Allyl-Radikal umlagern, oder es stellt sich ein Gleichgewicht ein z. B.6 ... 

Both sides of acetone have been alkylated with different alkyl groups, in one operation, by treatment of the Al,lV-dimethylhydrazone of acetone with n-BuLi, followed by a primary alkyl, benzylic, or allylic bromide or iodide then another mole of n-BuLi, a second halide, and finally hydrolysis of the hydrazone. ... 

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

Phosphinous amides, based on proline and tetrahydroisoquinoline carboxylic acid, bearing a second donor center (50, Ar=Ph R =H, CH3,Tr, Ph R =H, CH3,Tr, Ph and 51, R =H,Tr R =H,Tr) (Scheme 40) have been developed for use in allylic alkylation and amination of substituted propenyl acetates, yielding the corresponding products in 87-98% (5-94% ee) and 29-97% (14-93% ee) respectively [55, 167]. With bidentate ligands of type 38 where R=(S)-PhMeCH, and with the bis(aminophosphanes) 52 (R=Ph) similar allylic alkylations have been also tested [168,169]. 

Using the above procedures, allyl a-azido alkyl ethers of type 281 were prepared by employing an unsaturated alcohol such as allyl alcohol [76] (Scheme 32). The reaction of an aldehyde with allyl alcohol and HN3 in a ratio of 1 3 9 carried out in the presence of TiCl4 as catalyst provided azido ethers 281, 283, and 285 in 70-90% yield. The ratio of reagents is critical to ensure a high yield of azido ether and to prevent formation of acetal and diazide side products [75]. Thermolysis of azido alkenes 281, 283, and 285 in benzene (the solvent of choice) for 6-20 h led to 2,5-dihydrooxazoles 282,284, and 286, respectively, in 66-90% yield. 

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