Triple asymmetric synthesis

The borolanyl triflate (eq 10) has also been employed to form the chiral boron enolates of methyl ketones which have additional chiral centers present in their carbon framework. Reaction of these enolates with chiral aldehydes constitutes a triple asymmetric synthesis , in which the approximate multiplicativity of the three diastereofacial selectivities appears to be valid. ... 

In 1994, Hanessian and co-workers [50] reported the first examples of metal-free three-dimensional triple-stranded helicates through spontaneous self-assembly of chiral C2-symmetrical diols and chiral C2-symmetrical diamines. The initial observation resulted from the utilization of enantiopure C2-symmetrical vicinal trans-1,2-diaminocyclohexane [51,52] as ligands in the asymmetric dihydroxylations of olefins [53] and as reagents for asymmetric synthesis [54], When equimolar amounts of (5,5)-frfl x-l,2-diaminocyclohexane (28) and its (i ,i )-enantiomer (29) were individually mixed with (5,5)-frfl x-l,2-cyclohexanediol and heated in refluxing benzene, crystals of the respective supraminol complexes 28 30 and 29 30 were formed quantitatively (Scheme 12). This was the physical basis for the separation of racemic diols with tr[Pg.104]

Enders D, Htittl MRM, Runsink J, Raabe G, Wendt B (2007b) Organocatalytic one pot asymmetric synthesis of functionalized tricyclic carbon skeletons via a triple cascade/Diels-Alder sequence. Angew Chem 119 471... 

A catalytic triple domino Michael-aldol-oxa-Michael reaction of acetaldehyde with ( -2-(2-nitrovinyl)phenols catalyzed by (R)-2- diphenyl [(trimethylsilyl)oxy] methyl pyrrolidine followed by a sequential one-pot Wittig, Michael/Wittig-Horner reactions with PPh3=CHC02Et was applied to the asymmetric synthesis of polyfunctionalized chromans (14EJO3076). 

The absolute configurations of the sulfoxides resulting from the asymmetric oxidation of sulfides are safely predicted by the method shown in Scheme 1.7. In aryl methyl sulfides, one takes aryl as the large (L) group. For methyl alkyl sulfides, it is the methyl group which is the smaller. 7t-Systems play a special role, as often encountered in asymmetric synthesis thus in the oxidation of Me— C=C—Bu", the triple bond has to be taken as the (L) group [54,55]. 

Arylrhodium species undergo facile intermolecular 1,2-addition across carbon-carbon triple bonds, with the resulting alkenyl rhodium intermediate providing an entry point for further cascade reactions [121]. As an example, Hayashi applied this concept to the asymmetric synthesis of a number of cycloalkanols 157 starting from ynals 155 and arylboronic acids (Scheme 8.43) [122]. TransmetaUation of the... 

Enders described a fascinating organocatalytic one-pot asymmetric synthesis of tricyclic compounds using a triple-cascade/Diels-Alder reaction sequence. Combination of dieneal 110 with enal 111 and nitro alkene 112 in the presence of a chiral amine catalyst results in a Michael/Michael/aldol condensation sequence to yield cycloaddition precursor 113. Cooling the reaction mixture and addition of a Lewis acid promotes the desired intramolecular Diels-Alder reaction to selectively afford the highly functionalized tricyclic target 114. ... 

D. Enders, B. Schmid, N. Erdmann, G. Raabe, Synthesis 2010, 13, 2271-2277. Asymmetric synthesis of thiadecalins via an organocatalytic triple cascade/sulfa-Michael sequence. 

Boukouvalas and co-workers employed an intramolecular oxycarbonylation of benzyl alcohol 89 in the asymmetric synthesis of (—)-panacene, tetrahydrofuroben-zofuran derivative, which holds the prominent position of being the archetypical member of a family of marine bro-moallenes. ° The synthesis of the panacene building block 89 (Scheme 15.22) starts from the aldehyde 87, which is accessed from commercially available 2-methoxy-6-metyl-benzoic acid. An asymmetric alkynylation of 87 followed by reduction of the triple bond with hydrogen over Lindlar... 

Since Huisgen s definition of the general concepts of 1,3-dipolar cycloaddition, this class of reaction has been used extensively in organic synthesis. Nitro compounds can participate in 1,3-dipolar cycloaddition as sources of 1,3-dipoles such as nitronates or nitroxides. Because the reaction of nitrones can be compared with that of nitronates, recent development of nitrones in organic synthesis is briefly summarized. 1,3-Dipolar cycloadditions to a double bond or a triple bond lead to five-membered heterocyclic compounds (Scheme 8.12). There are many excellent reviews on 1,3-dipolar cycloaddition, in particular, the monograph by Torssell covers this topic comprehensively. This chapter describes only recent progress in this field. Many papers have appeared after the comprehensive monograph by Torssell. Here, the natural product synthesis and asymmetric 1,3-dipolar cycloaddition are emphasized.630 Synthesis of pyrrolidine and -izidine alkaloids based on cycloaddition reactions are also discussed in this chapter. 

Metal-catalyzed C-H bond formation through isomerization, especially asymmetric variant of that, is highly useful in organic synthesis. The most successful example is no doubt the enantioselective isomerization of allylamines catalyzed by Rh(i)/TolBINAP complex, which was applied to the industrial synthesis of (—)-menthol. A highly enantioselective isomerization of allylic alcohols was also developed using Rh(l)/phosphaferrocene complex. Despite these successful examples, an enantioselective isomerization of unfunctionalized alkenes and metal-catalyzed isomerization of acetylenic triple bonds has not been extensively studied. Future developments of new catalysts and ligands for these reactions will enhance the synthetic utility of the metal-catalyzed isomerization reaction. 

At the end of the previous chapter, we discussed the medium dependence of the lipase-catalyzed synthesis of nifedipines, dihydropyridines with an aromatic substituent in the 4-position and often asymmetric ester derivatives in the 3- and 5-positions, which are active as calcium antagonists in cardiovascular therapy. At the Amano Company in Nagoya, Japan, lipase-catalyzed hydrolyses of methylene-oxypropionyl or -pivaloyl diesters with Amano PS (Pseudomonas sp.) lipase were found to yield varying enantiomeric excesses depending on the solvent in cyclohexane the different esters yielded half-esters with 88.8-91.4% e.e. (R)-specificity for a triple mutant ( FVL ) of Amano PS lipase, whereas the same transformation with the same enzyme in diisopropyl ether (DIPE) yielded between 68.1 and > 99% e.e. of the (S)-product (Chapter 12, Figure 12.10) (Hirose, 1992,1995). 

The final approach was elegantly presented by Panek [44]. Several optically active ( )-crotylsilanes are available via stereoselective Ireland-Claisen rearrangement of enantiomerically pure vinylsilanes. Addition of the chiral crotylsilanes to acetals or to mixtures of aldehyde and trimethylsilyl methyl ether is effected by la to afford homoallylic ethers in exceedingly high diastereo- and enantioselectivity (Sch. 13). Occasionally a stoichiometric amount of la is required for allylation of aliphatic acetals, preserving the excellent level of asymmetric induction. The synthesis of (-F)-macbecin I involving triple use of the strategy imderscores the utility of the la-catalyzed asymmetric allylation [44c]. 

---