3.6- Dimethoxy-2-isopropyl-5- 2- methyl- -2,5-dihydro

With chiral racemic oxiranes one enantiomer reacts faster than the other the degree of kinetic resolution is very high for L-valine/alanine-based dialkoxydihydropyrazines. For example, in the reaction of one equivalent of (2.S )-2,5-dihydro-2-isopropyl-3,6-dimethoxy-5-methyl-pyrazine (1, R1 = CH3) with two equivalents of fW-(//,/ )-2,3-dimethyloxirane (R2,R4 = CH3 R = H) virtually only the (2//,3/ )-oxirane enantiomer reacts with the lithiated dihydropyrazine to give exclusively the (l /, 2/, 2 / )-configuratcd adduct i.e., (2/ ,5S)-2,5-dihydro-5-isopropyl-3,6-dimethoxy-2-[(l/ ,2/ )-2-(2-methoxyethoxymethoxy)-l-methylpropyl]-2-methylpyrazine, entry 7. Likewise, kinetic resolution (intramolecular) occurs upon reaction with rac-7-oxabicy-clo[4.1.0]heptane (entry 8). 

Bromomethyl-5-isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydropyrazine (272) gave 2-isopropyl-3,7-dimethoxy-6-methyl-2//-diazepine (273) and/or the isomeric 2-isopropylidcnc-3,7-diincthoxy-6-methyl-5,6-dihydro-2//-diazcpinc (274) [Bu OK, Mc2SO, 50°C, 1 h 0 and 75%, respectively KOH, Me2SO, 25°C, 24 h 73% and 6%, respectively KOH, Mc2SO, 50°C, 5 h 93% and trace, respectively the kinetics and mechanism have been studied].923... 

Isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydro-2-pyrazinecarbaldehyde (275) gave 2-(2,2-dibromovinyl)-5-isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydropy-razine (276) (CBr4, PPh3, CH2C12, 0°C, A, 30 min then substrate j, 4 h ... 

A soln. of 2,4,6-trimethoxytoluene in isobutyric acid satd. with BFg, and the product isolated after 1 hr. 2,2-difluoro-l,2-dihydro-4-isopropyl-5,7-dimethoxy-8-methyl-l-oxa-3-oxonia-2-boratanaphthalene (Y 76%) suspended in 4 1 methanol-water, and stirred 1 hr. at 50° baeckeol (Y 96%). F. e. s. G. P. Schiemenz and U. Schmidt, A. 1976,1514. 

In contrast, when a twofold excess of the dialkoxydihydropyrazine is used, then 2 1 adducts are obtained. This has been demonstrated18 by reacting A,7V-bis(2-iodoethyl)-4-methylben-zenesulfonamide with two equivalents of the lithiated D-valine/alanine-based dialkoxydihydropyrazine 8 to give 7V.fV-bis 2-[(2S,57 )-2,5-dihydro-5-isopropyl-3,6-dimethoxy-2-mcthyl-2-pyrazinyl]ethyl -4-methylbenzenesulfonamide (9) in high yield and >95% de. The adduct can be hydrolyzed in high yield to the corresponding amino acid methyl ester 10. 

Pyrazin 3,6-Dimethoxy-2-isopropyl-5-(l -methyl-2-nitro-ethyl)-2,5-dihydro- E16d, 441 (Michael-Addition)... 

Dimethoxy-2-( 1 -hydroxy-ethyl )-5-isopropyl-2-methyl-2,5-dihydro- E21b, 1770 [2-H - 2-CH(OH)-CH3]... 

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