Enantioselectivity insertion

Either or both myrcene and 5-hydroxygeranyl diphosphate are then converted to ipsdienol, or 5-hydroxygeranyl diphosphate is converted to ipsdienone via a ketone (5-keto-geranyl diphosphate) intermediate. As outlined in Vanderwel (1991), ipsdienol can be converted directly or via other ketone intermediates to ipsenol. Note that the ultimate enantiomeric composition of ipsdienol may result from the enantioselective insertion of a hydroxyl group at C5 of geranyl diphosphate or from an enantioselective interconversion of ipsdienol and ipsdienone (modified from Fish etal., 1984 Vanderwel, 1991). For intermediates in this pathway, OPP denotes a diphosphate moiety. Figure adapted from Seybold et al. (2000). 

Chiral dirhodium complex 87 (see Section 7.04.2.4) catalyzes the diastereo- and enantioselective insertion of phenyldiazoacetate 251 into 1,2,3,6-tetrahydropyridine 252 to give predominantly the erythro 6-substituted-l,2,3,6-tetrahydropyridine 253 with high enantiomeric selectivity. The threo-isomex 254 is a minor product and was formed with much lower selectivity (Equation 24) <1999JA6509, 2001TL3149>. 

Scheme 6. A schematic process for the enantioselective insertion of 2,3-dihydro-furan into the Pd-Ph bond in [PdPh (/ )-BINAP ]+ species, showing the two possible modes (a) and (b) for olefin-coordination. The binaphthyl group in (R)-BINAP ligand is omitted for clarity.

Table 10. Pentad Analysis, Bernoullian Probability of Enantioselective Insertion (b), and Probability of ...

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

The most useful of the insertion processes is the intramolecular reactions that occur with high selectivity for the formation of five-membered ring products. The electrophilic nature of the process is suggested by C-H bond reactivity in competitive experiments (3°>20 >1°) [76, 77]. Asymmetric catalysis with Rh2(MPPIM)4 has been used to prepare a wide variety of lignans that include (-)-enterolactone (3) [8], as well as (R)-(-)-baclofen (2) [7],2-deoxyxylolactone (31) [80,81],and (S)-(+)-imperanane (32) [82].Enantioselectivities are 91-96%... 

This methodology has provided an alternative, highly enantioselective route to sertraline 1 [94]. Insertion into the oxygen-activated CH2 position of allyl ethers yields syn-aldol products with high stereocontrol (Eq. 13) [97], and... 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

In one case, the insertion of the whole chiral hgand into a Co-exchanged zeohte by subhmation was described [24], Only small ligands, such as li and 2i, can be efficiently introduced into the micropores of the Y zeohte, whereas the bulkier Jacobsen s hgand la only remains on the external surface of the sohd. Unfortunately, these occluded (salen)Co complexes led to very low enantioselectivities (up to 8% ee) in the reduction of acetophenone with NaBH4. 

The enantioselective P-borylation of a,P-unsaturated esters with (Bpin) was studied in the presence of various [CuCl(NHC)] or [Cu(MeCN)(NHC)] (NHC = chiral imidazol-2-ylidene or imidazolidin-2-ylidene) complexes. The reaction proceeds by heterolytic cleavage of the B-B bond of the (Bpin), followed by formation of Cu-boryl complexes which insert across the C=C bond of the unsaturated ester. Best yields and ee were observed with complex 144, featuring a non-C2 symmetric NHC ligand (Scheme 2.31) [114]. 

In the same area, good levels of enantioselectivity have been achieved in intramolecular C H insertion reactions of a-diazocarbonyl compounds... 

As another extension of this process, Davies et al. have developed highly regio-, diastereo- and enantioselective C-H insertions of methyl aryldiazoace-tates into cyclic A-Boc-protected amines catalysed by rhodium(II) S)-N- p-dodecylphenyl)sulfonylprolinate. The best results were obtained in the case of the C-H insertion of methyl aryldiazoacetates into A-Boc-pyrrolidine, which gave, in all cases, a diastereoselectivity and an enantioselectivity greater than 90% de and 90% ee respectively (Scheme 10.77). The synthetic utility of this method was demonstrated by means of a two-step asymmetric synthesis of a novel class of C2-symmetric amines. 

A further example of highly diastereoseleetive and enantioseleetive C-H insertions performed in similar eonditions to those deseribed above was the reaetion between aryldiazoacetates and allylsilyl ethers, yielding p-hydroxy ester derivatives that are equivalents to aldol products. " An illustrative reaction between an aryldiazoacetate and trani-2-butenylsilyl ether is shown in Scheme 10.78. This reaction led to the diastereoseleetive formation of the equivalent of a syn-a do product in both high yield and enantioselectivity. 

Polymerization of triphenylmethyl methacrylate in the presence of a chiral anion catalyst results in a polymer with a helical structure that can be coated onto macroporous silica [742,804). Enantioselectivity in this case results from insertion and fitting of the analyte into the helical cavity. Aromatic compounds and molecules with a rigid nonplanar structure are often well resolved on this phase. The triphenylmethyl methacrylate polymers are normally used with eluents containing methanol or mixtures of hexane and 2-propanol. The polymers are soluble in aromatic hydrocarbons, chlorinated hydrocarbons and tetrahydrofuran which, therefore, are not suitable eluents. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Waymouth and coworkers used chiral zirconocene complexes such as 56 with Et3Al as the stoichiometric reductant to enantioselectively desymmeter-ize oxabicyclic compounds (Scheme 9) [29]. A reductive coupling mechanism to give 57 followed by (i-alkoxidc ring opening and transmetallation is consistent with the experimental results. Neither direct insertion of the alkene into the M - C bond nor nucleophilic attack mechanisms can be ruled out, however [12]. 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

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