Diastereoselective synthesis triple

Diastereoselective synthesis of compounds (259) has been accomplished by an application of a-acylaminoradical cyclization at a silylated triple bond in compound (258) <86CL735>. Desilylation of (259) (TFA-CH2CI2) gave a quantitative yield of (260) as a single diastereoisomer. A similar reaction of the aldehyde (261) with tributyltin hydride in presence of AIBN gave a mixture of diastereoisomers (262) and (263) in 86% yield (without diastereoselectivity at the C-7 position). A particularly noteworthy feature is that the radical cyclization proceeds with complete facial selectivity <94CC1383>. These reactions are shown in Scheme 45. 

The first diastereoselective synthesis of methyl (3R,7R)-jasmonate is attributed to Gerhard Quinkert. [94] In the initial step, starting from bis-(8-phenyhnen-thyl) malonate, a vinylcydopropane is constructed. After removal of the chiral auxiliary, the cyclopentanone is built up by means of a domino homo-Michael reaction / Dieckmann cydisation. Attack of dimethyl pent-2-ynylmalonate leads to inversion at the stereogenic centre at the vinyl cyclopropane. After decarboxylation, the vinyl residue is transformed into an ester group and the triple bond hydrogenated with a Lindlar catalyst. 

In addition, the same research group has carried out the diastereoselective synthesis of a-phospharyl-substituted 2-ethylphosphaferrocenes."" New triple-decker complexes 77 G4Me4P)(FeCp )(MGp )](BF4) (M = Rh, Ir)... 

Keck and Wagner used a diastereoselective thiyl radical addition/cyclization sequence to generate the key compound 157 for a total synthesis of ewMycoricine 158 (Scheme 2.28). In this sequence, photogenerated PhS undergo exclusive addition at the p-site of the C = C triple bond in the starting alkyne 156 to produce the resonance-stabilized vinyl radical 159 (interestingly, with BusSn, ... 

The solution-phase synthesis and resolution of new phosphinopeptidic building blocks containing a triple bond and their involvement in 1,3-dipolar cycloaddition with a variety of in j// -prepared nitrile oxides allowed the diastereoselective preparation of a novel class of isoxazole-containing phosphinic peptides 619. Inhibition assays of some of these peptides revealed their behavior as very potent inhibitors of metalloproteases, outmatching previously reported phosphinic peptides in terms of potency <2003CEJ2079>. 

Chiral sulfoxides with a pyridine substituent 16 are useful chiral dienophiles (Section D. 1.6.1.1.1.1.2.2.). The synthesis starts with the (—)-menthyl ester of propynoic acid which undergoes addition of 2-pyridinethiol to the triple bond. The oxidation of the sulfur occurs with some diastereoselectivity and the isomers are separated by crystallization from hexane16. 

The Conia-ene reaction of P-ketoesters bearing a pendant triple bond involves the cycloisomerization of an enyne formed by enolization. This transformation is efficiently catalyzed by cationic gold(I) complexes and afforded cyclopentane derivatives with excellent yields and moderate to good diastereoselectivities (Scheme 4-40). Acetylenic silyl enol ethers or imines react in an analogous manner. By this method, iodoalkynes were converted into iodocyclopentenes, which are highly useful in natural product synthesis. 

The main stereoselective MBFTs for the synthesis of spirocyclic acetals or aminals involve the activation of a C-C triple bond to form an intermediate cyclic enol ether. The method disclosed above for the synthesis of a-heteroatom-substituted spirocen-ter (see Section 9.3.3, Scheme 9.18) [34] was next extended by the same authors to the synthesis of spiroacetals. They simply used salicyladehyde as starting aldehyde, but the transformation was not diastereoselective anymore [43]. This problem of stereoselectivity was recently solved by Gong and coworkers, who employed a gold(I)/chiral Brpnsted acid catalysis to do so [44], The chroman spiroacetals were obtained in excellent yields (67-97%) and with high stereoselectivities (up to 95% ee, up to 25 1 dr) (Scheme 9.24). This reaction resulted in the formation of three new single bonds and two stereogenic centers. 

The asynunetric organocatalytic triple cascade reaction for the synthesis of telrasu-bstituted cyclohexene carbaldehydes developed by Enders et al. (Scheme 1.30) [40] is a milestone of organocatalytic cascade reactions. This three-component domino reaction proceeds by way of a catalyzed Michael-Michael-aldol condensation sequence affording products in good to moderate yields (25 to 58%). Notably, four stereogenic centers are formed with high diastereoselectivity and complete enantioselectivity. 

---