AROM reactions

The appreciable levels of asymmetric induction observed in the catalytic ARCM reactions mentioned above suggest a high degree of enantiodifferentiation in the association of olefinic substrates and chiral complexes. This stereochemical induction may also be exploited in asymmetric ring-opening metathesis (AROM). Catalytic ROM transformations [20] offer unique and powerful methods for the preparation of complex molecules [2d, 2g]. The chiral Mo-alkyli-denes that are products of AROM reactions can be trapped either intramolecu-larly (RCM) or intermolecularly (cross metathesis, CM) to afford a range of optically enriched adducts. 

Transformations shown in Schemes 12-14 constitute the first examples of catalytic AROM reactions ever reported. Meso-triene 50 is converted to chiral heterocyclic triene 32 in 92% ee and 68% yield in the presence of 5 mol % 4a (Scheme 12) [21]. Presumably, stereoselective approach of the more reactive cy-clobutenyl alkene in the manner shown in Scheme 12 (II) leads to the enantioselective formation of Mo-alkylidene III, which in turns reacts with an adjacent terminal olefin to deliver 51. Another example in Scheme 12 involves the net rearrangement of meso-bicycle 52 to bicyclic structure 54 in 92% ee and 85% yield. The reaction is promoted by 5 mol % 4a and requires the presence of di-... 

Recently, Floveyda and Schrock have developed molybdenum-based catalysts (i.e. 744a,b) for an asymmetric ring-opening metathesis (AROM) reaction (Scheme 121) (98JA4041, 98JA9720, 99JA11603). Using a tandem AROM/RCM sequence, they examined the asymmetric synthesis of several heterocyclic compounds. For example,... 

More complex heterocyclic structures have been synthesized efficiently and with high stereoselectivities using tandem AROM-RCM sequences [85] similarly, application of tandem AROM/CM to functionalized norbomenes affords enantio-pure highly functionalized cydopentanes [86]. A polymer-supported chiral molybdenum catalyst for enantioselective metathesis effidendy promotes ARCM (kinetic resolution as well as desymmetrization) and AROM reactions and can be recycled [87]. 

A solution of the sodium salt of yV-methylaniline in HMPA can be used to cleave the methyl group from aryl methyl ethers ArOMe + PhNMe —> ArO + PhNMca- This reagent also cleaves benzylic groups. In a similar reaction, methyl groups of aryl methyl ethers can be cleaved with lithium diphenylphosphide (PH2PLi). " This reaction is specific for methyl ethers and can be carried out in the presence of ethyl ethers with high selectivity. 

Ruppe S, A Neumann, W Vetter (2003) Anaerobic transformation of compounds of technical toxaphene. I. Regiospecific reaction of chlorobomanes with geminal chlorine aroms. Environ Toxicol Chem 22 2614-2621. 

Reactions carried out over a catalytic bed of PEG 1000 (300 g) and K2CO3 (6 g). Molar ratios ArOH DMC were 1 1.05 and 1 1.5 for PhOH and p-MeCgH40H, respectively. WHSV grams of ArOMe obtained hourly per gram of catalyst. 

The new catalyst is developed from commercially available starting materials and can be used in situ without isolation, to effect enantioselective olehn metathesis [Eq. (6.69)]. An active catalyst solution can be accessed by premixing of readily available (7 )-102, and a commercially available Mo-triflate 103 and can be used directly without further purification. This catalyst solution promotes ARCM reactions with equal or higher levels of efficiency and selectivity than does 75a. Desymmetrization of 80c with THE solution of 77 gave furan derivative 81c with 88% ee. Use of 75a gave 81c with 93% ee [Eq. (6.70)] similarly, AROM-CM of norbomene 82e gave cyclopentane derivative (R)-83e with 98% ee ... 

Atomic (or Nuclear) Energy Atomic (or Nuclear) Reactions Atomic (or Nuclear) Explosions. In chemical reactions the atomic nuclei maintain their charges, masses, and individual identities. These all change in aromic or nuclear reactions, first revealed in the discovery of radioactivity by Becquerel in 1895 and of radium by the Curies in 1898. 

With the above considerations in mind, we prepared and examined a myriad of chiral Mo-based catalysts for both asymmetric RCM (ARCM) and ROM (AROM) transformations [5]. In this article, several efficient and enantioselec-tive reactions that are catalyzed by these chiral complexes are discussed [6]. The structural modularity inherent to the Mo-based systems allows screening of catalyst pools, so that optimal reactivity and selectivity levels are identified expeditiously. 

The chiral Mo-alkylidene complex derived from AROM of a cyclic olefin may also participate in an intermolecular cross metathesis reaction. As depicted in Scheme 16, treatment of meso-72a with a solution of 5 mol % 4a and 2 equivalents of styrene leads to the formation of optically pure 73 in 57% isolated yield and >98% trans olefin selectivity [26]. The Mo-catalyzed AROM/CM reaction can be carried out in the presence of vinylsilanes the derived optically pure 74 (Scheme 16) may subsequently be subjected to Pd-catalyzed cross-coupling reactions, allowing access to a wider range of optically pure cyclopentanes. 

The Mo-catalyzed AROM/CM can be effected on highly functionalized nor-bornyl substrates (e.g., 76 and 77 in Scheme 17) and those that bear tertiary ether sites (e.g., 79-81). Although initial studies indicate that the relative orientation of the heteroatom substituent versus the reacting olefin can have a significant influence on reaction efficiency, the products shown in Scheme 17 repre-... 

More recently, we have synthesized and studied the activity of 89, the first supported chiral catalyst for olefin metathesis (Scheme 20) [28]. Catalyst 89 efficiently promotes a range of ARCM and AROM processes a representative example is shown in Scheme 20. Rates of reaction are lower than observed with the corresponding monomeric complex, but similar levels of enantioselectivity are observed. Although 89 must be kept under rigorously dry and oxygen-free conditions, it can be recycled. Catalyst activity, however, is notably diminished by the third cycle. As the data and the figure in Scheme 20 show, the product solution obtained by filtration contains significantly lower levels of metal impu-... 

Scheme 21. Air-stable chiral Ru-based catalyst for olefin metathesis can be used for highly effective and selective AROM/CM reactions...

The chiral Mo-alkylidene complex derived from AROM of a cyclic olefin may also participate in an intermolecular cross metathesis reaction. As depicted in Scheme 15, treatment of meso-67a with a solution of 5 mol% 4a and 2 equivalents of styrene leads to the forma-... 

The asymmetric reactions can also be coupled with achiral metathesis reactions as in, for example, AROM/RCM or AROM/CM reactions.66,67 Examples of the latter are given in Scheme 28.22.68-70... 

This methodology has been applied to the synthesis of the dihydropyran portion 32 of tipranavir (33), an anti-human immunodeficiency virus compound (Scheme 28.23).56-70 The dihydropyran 32 can be accessed from the cyclopentene 34 by what is formally a tandem AROM/RCM reaction. 

Conversion of l,l-dichloro-2,3-diphenyl-l-germaindene to the lithium (or sodium) dianion according to reaction 21 in THF-TMEDA led to an unusual phenomenon of arom-atization of the GeC4 portion of 1-germaindene at the expense of the aromatic Cg 37... 

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