Reduction stereocontrolled

The first of these alternative approaches started with commercially available indanone-3-carboxylic acid 23 (derived from phenylsuccinic anhydride via Friedel-Crafts chemistry). This indanone was a viable precursor to 6 through an aminomethyl homologation with cyanide or nitromethane (Scheme 3.10). Our intent was to obtain ester 25, which after reduction would afford methylamine 28, which in turn would cyclize to generate lactam 29, giving benzazepine 6 upon reduction. Stereocontrol in the homologation was unnecessary, as lactam 29 would theoretically provide a thermodynamic sink under epimerizing reaction conditions, capturing the desired di-indane isomer. 

It was anticipated that two of the three stereochemical relationships required for intermediate 12 could be created through reaction of the boron enolate derived from imide 21 with a-(benzyloxy)ace-taldehyde 24. After conversion of the syn aldol adduct into enone 23, a substrate-stereocontrolled 1,2-reduction of the C-5 ketone car-... 

Diketimines can be prepared by condensation of 1,2-diketones with 2 equiv of an amine, or 1 equiv of a 1,2-diamine, by azeotropic removal of water. Either a chiral diketone or a chiral amine/diamine can be used in order to obtain a chiral diimine. In both cases, the use of 1,2-diamines is expected to provide better stereocontrol, because of the rigidity of the derived cyclic diimines. For example, the reaction of camphor 1,2-diketone 275 and racemic 1,2-diphenylethylenediamine (d,l)-26 gave the diimine 276 as a mixture of two diastereomers (Scheme 45) [138]. Reduction of 276 with sodium borohydride followed by hydrogenolysis of the N substituents afforded the camphordiamine, which was isolated as the dihydrochloride... 

The synthesis in Scheme 13.21 starts with a lactone that is available in enantiomer-ically pure form. It was first subjected to an enolate alkylation that was stereocontrolled by the convex shape of the cis ring junction (Step A). A stereospecific Pd-mediated allylic substitution followed by LiAlH4 reduction generated the first key intermediate (Step B). This compound was oxidized with NaI04, converted to the methyl ester, and subjected to a base-catalyzed conjugation. After oxidation of the primary alcohol to an aldehyde, a Wittig-Horner olefination completed the side chain. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

In a related cobalt-catalyzed transformation, 1,3-dienes tethered to ally lie ethers engage in Et2AlCl-mediated reductive cyclization.463 Exposure of benzylic ether 22a to Co(acac)3-PPh3 in the presence of Et2AlCl results in formation of divinylcyclopentane 22b with excellent /raar-diastereoselectivity. As demonstrated by the conversion of 23a to 23b, this method is also applicable to the stereocontrolled formation of six-membered rings (Scheme 16). 

The stereocontrol and functional group tolerance exhibited by the palladium-catalyzed silane-mediated reductive enyne cyclization has led to its use as a key bond formation en route to structurally complex natural products. These include /3-necrodol,59 (—)-4a,5-dihydrostreptazolin,S9b ( )-laurene,S9c and, as illustrated by the conversion of 1,6-enyne 35a to furan 35b, ( )-phyllanthocin (Scheme 25).S9a... 

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