Reaction selectivity, alkylideneally

Mukaiyama Michael reactions of alkylidene malonates and enolsilanes have also been examined (244). The stoichiometric reaction between enolsilane (342a) and alkylidene malonate (383) proceeds in high selectivity however, catalyst turnover is not observed under these conditions. The addition of HFIP effectively promotes catalyst turnover, presumably by protonation and silyl transfer from the putative copper malonyl enolate generated in this reaction. The reaction proved general for bulky P-substituents (aryl, branched alkyl), Eq. 209. 

The synthesis of capnellene discussed earlier is an interesting example in which (3) was used to generate a new titanium alkylidene which then underwent an intramolecular reaction with an ester carbonyl. The process effectively involved carbonyl alkylidenation by a substituted titanium alkylidene (equation 14). In this case steric factors apparently account for the desired reaction selectivity. ... 

Inokuchi, T., Okano, M., Miyamoto, T. Catalyzed Diels-Alder Reaction of Alkylidene- or Arylideneacetoacetates and Danishefsky s Dienes with Lanthanide Salts Aimed at Selective Synthesis of cis-4,5-Dimethyl-2-cyclohexenone Derivatives. J. Org. Chem. 2001,66, 8059-8063. 

In 2008, Enders and coworkers reported the first high-yielding enantioselective intermolecular Stetter reactions employing chalcones and aryUdene-malonates as acceptors and N-Bn triazolium salt 71 as precatalyst (Schemes 18.11 and 18.12) [48]. The use of an N-benzyl instead of the usual N-aryl substituent on the triazolium ring was crucial for the activity and selectivity of the catalyst. Rovis et al. subsequently disclosed a highly enantioselective Stetter reaction of alkylidene-... 

Transacetalation of 5-O-substituted 1,2-O-alkylidene-D-gluco-furanurono-6,3-lactones is a reaction particularly suited to the synthesis of selectively protected D-glucofuranosidurono-6,3-lactones.34... 

Many of the studies concerning ring-opening metathesis by well-characterized metathesis catalysts have employed substituted norbornenes or norborna-dienes. Substituted norbornenes and norbornadienes are readily available in wide variety, and they usually react irreversibly with an alkylidene. Norbornene itself is the most reactive, and the resulting polynorbornene probably is the most susceptible to secondary metathesis. Formation of polynorbornene often is used as the test reaction for ROMP activity. ROMP by well-defined species has been reviewed relatively recently [30], so only highlights and selected background material will be covered here. 

As expected, there was no formation of stilbenes or a dinitrile product and, more surprisingly, in all of the reactions reported only 5-7% of the allyltrimeth-ylsilane self-metathesis product was observed. It was proposed that this lack of allylsilane self-metathesis was due to the steric bulk of the TMS group reducing the reactivity of the Me3SiCH2 substituted alkylidene. In a more recent report by Blechert and co-workers it was noted that allyltrimethylsilane and its hydrocarbon equivalent (4,4-dimethylpent-l-ene) had comparable reactivities in the cross-metathesis reaction [28], further suggesting that the selectivity arises from steric rather than electronic effects. 

Snapper proposed that the selectivity for the formation of cross-metathesis products 41 observed in these reactions was due to the differing reactivities of the various ruthenium alkylidene species formed in the catalytic cycle (Scheme 6). 

A subsequent publication by Blechert and co-workers demonstrated that the molybdenum alkylidene 3 and the ruthenium benzylidene 17 were also active catalysts for ring-opening cross-metathesis reactions [50]. Norbornene and 7-oxanorbornene derivatives underwent selective ring-opening cross-metathesis with a variety of terminal acyclic alkenes including acrylonitrile, an allylsilane, an allyl stannane and allyl cyanide (for example Eq. 34). 

Reactions with other gem-diiodoalkanes under these conditions proceed in low yield however, addition of DMF (and ultrasonic irradiation) provides a very general method for alkylidenation of aldehydes with good (E)-selectivity (equation II). 

Dihydro-4//-l,3-thiazines 231 are conveniently prepared by the iodocyclization of A -homoallyl thioamides 230 in the presence of triethylamine (Scheme 28) <2004CL508>. The selectivity of the reaction was dependent on the groups attached to the thioamide, and high diastereoselectivities are achieved with the 1-naphthyl or the 2-methoxyphenyl groups giving the major product 233 with the aryl group in the equatorial position rather than 234. Treatment of thiazines 231 with pyrrolidine resulted in the formation of 6-alkylidene-5,6-dihydro-4//-l,3-thiazines 232. 

As illustrated above, various possible alkylidene intermediates and numerous primary and secondary pathways are involved in olefin CM. To simplify selective reaction design, an empirical product selectivity model was recently developed by Grubbs and co-workers, in which some degree of orthogonality amongst olefin cross-partners was established by categorizing the relative capacity of olefins to homodimerize in the presence of a given metathesis catalyst. ... 

Lactone 5 can be obtained in both enantiomeric forms or as a racemate according to the described procedure. The reaction sequence includes the in situ formation of an alkylidene-1,3-dicarbonyl system 7 which can act as a heterodiene in an intramolecular hetero-Diels-Alder addition. A small amount of the ene product 4 with de > 98% is formed at room temperature as well. The remarkable selectivity in formation of diastereomer 3 is explained by an energetically more favorable exo transition state 8 with a pseudo-chair arrangement having the methyl group quasi-equatorial. Polycyclic cis-fused compounds can also be synthesized by the procedure above,9 and a related sequence to the cannabinoid skeleton has been described using appropriate 1,3-dicarbonyl reactants.10... 

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. 

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