Alkylation, regioselective allylic

A combination of rhodium complexes and phosphates promotes a highly regioselective allylic alkylation of unsym-metric allylic esters, where alkylation occurs at the more substituted allylic terminus of the esters (Equation (46)). As Evans and his co-workers reported, both the regio- and stereochemistry of the starting allylic esters are maintained in the allylic alkylated products (Equation (47)). Thus, the rhodium-catalyzed allylic alkylation takes place at the carbon substituted by a leaving group with net retention of configuration. A variety of carbon-centered... 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

In sharp contrast to the transition metal-catalyzed allylic alkylation of allylic alcohols and their derivatives (see Chapter 11.03) where 77 -allyl-transition metal complexes are key intermediates, the benzyiic alkylation of benzyiic alcohols and their derivatives catalyzed by transition metal complexes has been quite unexplored, although 7] -benzyl-transition metal complexes have often been considered to explain the regioselectivity of transition metal-catalyzed addition to vinylarenes (Scheme 21). A3,63a... 

Trimethylsilyl alkyl and aryl sulfides react with allyl carbonates and vinyl epoxides to deliver the alkyl or aryl sulfide to the allyl unit. These species show typical regioselectivities by (i) adding to the less substituted end of alkyl substituted allyls (equation 290) (ii) adding to the allyl terminus more distant from remote oxygen functionality (equation 291) and (iii) showing substantial endocyclic addition to methylenecyclohexane-derived allyls (equation 292).223... 

Alkylation of dihydropyranylacetates. The Pd(0)-catalyzed alkylation of allylic acetates by stabilized carbanions originally reported by Trost and Verhoeven (8,475 9, 451 -457)4 has been extended to alkylation of dihydropyranyl acetates as a route to natural C-glycopyranosides.5 Again the displacement is regioselective and results in net retention of configuration in reactions with most carbanions. However, alkylation with phenylzinc chloride or vinylzinc chloride occurs with inversion. 

The regioselective and enantiospecific allylic substitution of alkyl-substituted allyl benzoates and carbamates with (Me2PhSi)2Zn and Cul has been shown to occur by an oxidative addition - reduction elimination mechanism rather than an SN2 mechanism.16... 

An enantioselective rhodium(II)-catalysed intramolecular cyclopropanation, follow- (g) ed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalysed 5 + 2-cycloaddition has been reported.102 ... 

Alkylation ofaUylic ethers.2 PdCl2(dppf) is the most effective catalyst for alkylation of allyl trialkylsilyl ethers with Grignard reagents to give an internal alkene. NiCl2(dppf) also catalyzes this reaction, but with the opposite regioselectivity, thus forming a terminal alkene. 

Primary amines have been transformed into imines which when metallated react with carbonyl compounds. Treatment with butyllithium, alkylation with allyl bromide and hydrolysis gives highly substituted aldehydes (Scheme 6). Thus, in this example, the carbon adjacent to the original amino nitrogen atom becomes the carbonyl carbon. The technique has been used several times in the course of total synthesis, as with a recent approach to crinine and as the key step in a recent highly regioselective preparation of a,3 unsaturated aldehydes (equation 33). ... 

Alkylation of allylic alcohols. The alkyl substitution of allylic halides with allylic rearrangement by reagents of the type RCu-BFs (8, 334-335) can also be effected with allylic alcohols. However, in this case the alkylation is somewhat less regioselective and some a -substitution is also observed. On the other hand, allylic alcohols are more readily available than allylic halides. 

Copper salts such as CuCN, CuBr-SMc2 and CuCN-2LiCl were demonstrated to mediate the regioselective allylation, alkylation, and propargylation of the lithium anion of n-butylthiooxazole 128 providing 2,5-disubstituted systems 129. Desulfurization with deactivated W2-Raney nikel produced 5-substituted derivatives <03TL7395>. 

Recently, a new ruthenium catalyst that also provides regioselective allylic alkylation has been reported. In DMF, a highly branched alkylation product of cinnamyl carbonate vsdth malonate anion was obtained in quantitative yield (branched/line-ar = 14/1) within 30 min in the presence of 1 mol% of [(C5Me5)Ru(MeCN)3]PF6 catalyst (Eq. 5.30) [46]. 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Another methodology applied to the monosubstitution of diols is the use of copper complexation of dianions. The dianion is first formed by reaction of a diol with two equivalents of NaH. The copper complex is then formed by addition of a copper salt. Reaction of the copper complex with various electrophiles (alkyl halides, acyl chlorides) then gives the selectively protected products. As with the phase-transfer technique, very little disubstitution is observed. However, as illustrated in Scheme 3.16, the regioselectivity is reversed (i.e., 4,6-diols give mainly 4-substitution and 2,3-diols give mainly 3-substitution). Using this technique, both alkylations (benzylation, allylation) and acylations (acetylation, benzoylation, pivaloylation) have been carried out. As usual, the degree of selectivity depends on reaction conditions and structural factors [44]. 

A highly regioselective allylic substitution of allyl phosphates, with retention of the regiochemical integrity of the staring material (i.e., SN2-type alkylation, rather than Sn2 ) was reported [Eq. (Ill) 121]. This mode of substitution is in stark contrast to that of the copper-catalyzed one described in the foregoing section [see Eq. (54)]. 

Alkylation of allylic acetates. Regioselective monoalkylation of allylic acetates is possible by use of enol stannanes (prepared by reaction of lithium enolates with chlorotri-n-butyltin) in the presence of this Pd complex. The less substituted end of the allyl group is alkylated with formation of the (E)-isomer.4 Examples ... 

Alkylation of allylic alcohols. The alkylation of allylic alcohols by Grignard reagents in the presence of nickel-phosphine1-2 catalysts has been shown to be rtereospecific in the case of the cis- and ms-4-methyl-2-cyclohexene-l-ols (2)J. The hydroxyl group is replaced with inversion, but the regioselectivity is different. In... 

Allylic alkylations are among the most widely applied catalytic C-C bond formation reactions in organic chemistry. In the 1980s already mononitrosyl ferrate complexes of type 31 were reported to be active in regioselective allylic alkylations [94, 95]. However, this pioneering work suffered from low turnover numbers and the reaction had to be carried out under CO atmosphere. 

In further studies, Chou and colleagues found that the sulfolene nucleus could be regioselectively substituted with alkyl chains incorporating an alkene bond. Alkylations with allylic halides were particularly effective (Scheme 6.25, Table 6.8). They utilized this chemistry in neat syntheses of simple terpenes (see Section 6.4). In some cases the alkene bond of the side-chain was utilized as a dienophile in an intramolecular Diels-Alder reaction [43,46,69,109]. 

Palladium-catalyzed aUyUc alkylation of allyl dienol carbonates Reactivity, regioselectivity, enantioselectivity, and synthetic applications, particularly, straightforward access to di-, tri-, and tetrasubstituted furans and pyrroles 13SL2350. 

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