AROM/RCM

AROM)-RCM- and -CM sequences initiated by chiral molybdenum-based catalysts [194] or, more recently, also by ruthenium-based [195] catalysts. 

Catalytic Asymmetric Synthesis Through Tandem Mo-Catalyzed AROM/RCM... 

Scheme 12. Mo-catalyzed tandem AROM / RCM allows access to complex heterocyclic structures efficiently and in optically enriched form...

In contrast to 52 (Scheme 12), diastereomer 55 (Scheme 13), because of its more exposed and highly reactive strained olefin, undergoes rapid polymerization in the presence of 4a. The less reactive Ru complex 56 [23] can however be used under an atmosphere of ethylene to effect a tandem ROM/CM to generate 57. The resulting triene can be induced to undergo Mo-catalyzed ARCM (5 mol % 4a) to afford optically pure 58, the AROM/RCM product that would be obtained from 55. 

The Mo-catalyzed transformations shown in Scheme 14 may also be viewed as AROM/RCM processes [24], Furthermore, it is possible that initiation occurs at the terminal olefin, followed by an ARCM involving the cyclic alkene. Regardless of these mechanistic possibilities, the enantioselective rearrangements... 

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. 

Promising results were obtained for the AROM/RCM of norbomyl trienes with (97i) (ees up to 96% and 80% yield of the desired product were reported) (equation 25). 

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,... 

Asymmetric Ring-opening Metathesis (AROM) Sequence Hoveyda, Schrock, and co-workers applied their own asymmetric ring-opening/ring-closing metathesis (AROM/RCM) sequences to the total synthesis of... 

SCHEME 24.41. Total synthesis of the africanol using AROM/RCM. 

Ru-catalyzed AROM/CM sequences served as a key step in the total synthesis of baconipyrone C (163, Scheme 24.42), a marine polyketide isolated from Siphonaria baconi The employed Ru carbene [Ru]-VI is generated in situ by treatment of the achiral Ru-PCya complex with Ag-based V-heterocyclic carbene (NHC) and Nal. And then, the [Ru]-VI-catalyzed AROM/RCM of oxabicycle 161 with styrene (8 equiv) afforded the fully substituted pyran 162 in 62% yield and in 88% ee. The additional transformations led to 163 in good overall yield. Although this application of AROM/CM process to 161 was the first and rare example of Ru-catalyzed enantioselective olefin metathesis process, very recently, an application of enantioselective RCM reaction catalyzed by [Ru]-VII to the synthesis of (—)-5-e/>/-citreoviral has been reported by Funk. ... 

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]. 

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 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. 

Major advances were also made in the field of ARCM. Notable examples of this process are shown in Scheme 2 and include AROM <02JA10779>, and the desymmetrization reactions of acetals <00TL9553> and ethers <02JA2868>. Especially noteworthy are the ARCM to yield medium-sized, cyclic amines that occur in high yield and enantiomeric excess in the absence of solvent <01JA6991> [—m indicates the site of RCM]. 

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