Allylic stereospecificity

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Aryl halides react with a wide variety of aryl-, alkenyl- and alkylstan-nanes[548-550]. Coupling of an aryl tritlate with an arylstannane is a good preparative method for diaryls such as 688. The coupling of alkenylstannanes with alkenyl halides proceeds stereospecifically to give conjugated dienes 689. The allylstannane 690 is used for allylation[397,546,551-553]. Aryl and enol triflates react with organostannanes smoothly in the presence of LiCl[554]. 

Many examples of stereospecific allylation consistent with the above mechanism have been reported. As one example, the regioselective and highly diastereoselective allylation of the lactone 17 with the optically active allylic phosphate 16 proceeded with no appreciable racemization of the allylic part to give the lactones l8 and 19, and the reaction has been used for the synthesis of a polypropionate chain[26]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

An interesting feature of the synthesis is the use of allyl as a two-carbon extension unit. This has been used in the stereospecific synthesis of dicyclohexano-18-crown-6 (see Eq. 3.13) and by Cram for formation of an aldehyde unit (see Eq. 3.55). In the present case, mannitol bis-acetonide was converted into its allyl ether which was ozonized (reductive workup) to afford the bis-ethyleneoxy derivative. The latter two groups were tosylated and the derivative was allowed to react with its precursor to afford the chiral crown. The entire process is shown below in Eq. (3.59). 

When ethyl trifluoroacetylacetate is treated with an allylic alkoxide, tran-sesterification is followed by ester enolate Claisen rearrangement m a process that on decarboxylation yields stereospecifically the tnfluoromethyl ketone product [22] (equation 19)... 

Similar methodology has been used to prepare the dialkoxyphosphinyldi-fluoromethylcopper compound 242 (equation 160) Functionalization with allyl bromide, methyl iodide, and iodobenzene occurs readily, as well as stereospecific syn addibon to hexafluoro-2-butyne [243. ... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Halogen atoms can be stereoselectively introduced by ring-opening of y-azir-idinyl-a,P-enoates (Scheme 2.39). Treatment of 149 with diethylaminosulfur tri-fluoride (DAST) results in stereospecific ring-opening to yield fluorinated derivative 150 [59]. A related stereoselective conversion of y-aziridinyl-a,P-enoates 151 into allyl halides 152 by use of lithium halide in the presence of Amberlyst 15 was also reported recently [60]. 

The application of these catalysts in the initial state (without any special treatment of the surface organometallic complexes of such cata-lysts) for ethylene polymerization has been described above. The catalysts formed by the reaction of 7r-allyl compounds with Si02 and AUOj were found to be active in the polymerization of butadiene as well (8, 142). The stereospecificity of the supported catalyst differed from that of the initial ir-allyl compounds. n-Allyl complexes of Mo and W supported on silica were found to be active in olefin disproportionation (142a). 

Since its discovery two decades ago, the reversible interconversion of allylic sulfenates to sulfoxides has become one of the best known [2,3]-sigmatropic rearrangements. Certainly this is not only because of the considerable mechanistic and stereochemical interest involved, but also because of its remarkable synthetic utility as a key reaction in the stereospecific total synthesis of a variety of natural products such as steroids, prostaglandins, leukotrienes, etc. 

One of the first uses of the allylic sulfoxide-sulfenate interconversion was made by Jones and coworkers64, who reported exclusive suprafacial rearrangement of the allyl group in the steroidal sulfoxide 17 shown in equation 13. Two other examples are shown in equations 1465 and 1566. Evans and coworkers have demonstrated the utility of the suprafacial allylic sulfoxide-sulfenate rearrangement in a new synthesis of the tetracyclic alcohol 24 (equation 16)67, as well as in a synthesis of prostaglandin intermediates as shown in equation 1768. The stereospecific rearrangement of the unstable sulfenate intermediate obtained from the cis diol 25 indicates the suprafacial nature of this process. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

The evidence is in accord with an addition-elimination mechanism (addition of ArPdX followed by elimination of HPdX) in most cases. The reactions are stereospecific, yielding products expected from syn addition followed by syn elimination. Because the product is formed by an elimination step, with suitable substrates the double bond can go the other way, resulting in allylic rearrangement, for example, ... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

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