Stereospecific reactions insertion

Further supporting evidence for the occurrence of diradicals was obtained by Reich and Cram when they heated [2.2]paracyclophane with either dimethyl maleate or fumarate esters at 200 °C for 40 h in the absence of air. The cis- and trans-2,3-dicarboxymethyl[4.2]paracyclophanes 162 and 163 were formed in about equal amounts, irrespective of the configuration of the olefin employed. Other similar reactions would also suggest a radical mechanism for this reaction furthermore, a concerted addition of the olefinic double bond to 2, or to the postulated intermediate diradical 157, can be ruled out because of lack of stereospecificity of insertion. 

This mechanism implies that, if the C-H bond is at a stereogenic centre, the stereochemistry at that centre will be retained through the reaction, as in Cane s synthesis of pentalenolactone. A nice example of this result is the ingenious synthesis of a-cuparenone using a stereospecific carbene insertion. 

The stereochemistry of nitrene insertion into unactivated C—bonds has been studied using substituted cyclohexanes as substrates. For arylnitrenes which usually exhibit triplet reactivity, the reaction is nonspecific, but most other nitrenes undergo stereospecific C—insertion. For example, benzqylni-trene inserts selectively into the tertiary C—bond of toth cis and tra/u-1,4-dimethylcyclohexane with retention of configuration. Similarly with cis- and rra/is-l,2-dimethylcyclohexane as substrate, ethoxycarbonyl-, methatiesulfonyl- and cyano-nitrenes all insert with retention of configuration at the tertiary C—bond. 

The classical heterogeneously catalyzed propene polymerization as discovered hy Natta is a stereospecific reaction forming a polymer with isotactic microstructure. During the development of single-site polymerization catalysts it was found that C2-symmetric chiral metallocene complexes own the same stereospecificity. An analysis of the polymer microstructure hy means of NMR spectroscopy revealed that misinsertions are mostly corrected in the next insertion step, which suggests stereocontrol (Figure 6) hy the coordination site, as opposed to an inversion of stereospecificity hy control from the previous insertion steps (chain-end control). In addition, it was found that Cs-symmetric metallocene catalysts lead to syndio-tactic polymer since the Cosee-Arlmann chain flip mechanism induces an inversion of the stereospecificity at every insertion step. This type of polymer was inaccessible by classical heterogeneous systems. 

Full experimental details of the non-stereospecific ene-insertion reaction of hexafluorobutyne with 2,4-dimethylpenta-2,3-diene (see Vol. 2, p. 110) have appeared. An attempt to find a further example in the corresponding reaction of 3-methylbuta-l,2-diene was not successful in that only isomeric [2 + 2] cycloadducts were obtained. Since the isomer ratio in the latter reaction remains constant over the range 80—150 °C, a two-step mechanism for the cycloaddition was favoured. 

This conceptual link extends to surfaces that are not so obviously similar in stmcture to molecular species. For example, the early Ziegler catalysts for polymerization of propylene were a-TiCl. Today, supported Ti complexes are used instead (26,57). These catalysts are selective for stereospecific polymerization, giving high yields of isotactic polypropylene from propylene. The catalytic sites are beheved to be located at the edges of TiCl crystals. The surface stmctures have been inferred to incorporate anion vacancies that is, sites where CL ions are not present and where TL" ions are exposed (66). These cations exist in octahedral surroundings, The polymerization has been explained by a mechanism whereby the growing polymer chain and an adsorbed propylene bonded cis to it on the surface undergo an insertion reaction (67). In this respect, there is no essential difference between the explanation of the surface catalyzed polymerization and that catalyzed in solution. 

In the past few years metal deuterides have become commercially available at reasonable prices. This has encouraged the use of these reagents for reactions involving deuteride displacements of suitable leaving groups. The attractive feature of these reactions is the stereospecificity of the deuterium insertion. 

The stereochemistry of the insertion by (phenylthio)carbene to the a C-H bond of trans- and c/s-4-terr-butylcyclohexyloxides 16 was investigated19 to find that the reaction proceeds stereospecifically giving trans and cw-4-rert-butyl-l-methylcyclohexanol 19, respectively, after desulfurization of the primary insertion products 17 (Scheme 9). 

When the reaction of DMFL with alcohols, cyclohexane, or a-methylstyrene is initiated by triplet senitization, the outcome is virtually the same as it is for the direct irradiation. Thus ethers are formed in high yield with the alcohols, direct insertion accounts for the major product in cyclohexane, and the olefin cyclopropanation is stereospecific. 

The signature application for the G-H insertion in synthesis is probably the total synthesis of (—)-tetrodotoxin 126 by Du Bois and Hinman.233 Two stereospecific G-H activation steps, rhodium-catalyzed carbene G-H insertion and carbamate-based nitrene C-H insertion, have been used to install the two tetrasubstituted centers C6 and C8a (Scheme 12). Diazoketone 122 was treated with 1.5mol% Rh2(HNCOCPh3)4, and cyclic ketone 123 was selectively formed in high yield without purification. The reaction of carbamate 124 with 10mol% Rh2(HNCOCF3)4, PhI(OAc)4, and MgO in C6H6 solvent furnished the insertion product 125 in 77% yield. 

Insertion of phenyl, trimethylsilyl, and nitrile-stabilized metalated epoxides into zircona-cyclcs gives the product 160, generally in good yield (Scheme 3.37). With trimethylsilyl-substituted epoxides, the insertion/elimination has been shown to be stereospecific, whereas with nitrile-substituted epoxides it is not, presumably due to isomerization of the lithiated epoxide prior to insertion [86]. With lithiated trimethylsilyl-substituted epoxides, up to 25 % of a double insertion product, e. g. 161, is formed in the reaction with zirconacyclopentanes. Surprisingly, the ratio of mono- to bis-inserted products is little affected by the quantity of the carbenoid used. In the case of insertion of trimethylsilyl-substituted epoxides into zirconacydopentenes, no double insertion product is formed, but product 162, derived from elimination of Me3SiO , is formed to an extent of up to 26%. 

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