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

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. 

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). 

An interesting but not synthetically useful reaction has been reported by Mloston and co-workers <2002CEJ2184>. The treatment of 2,2,4,4-tetramethylcyclobutan-l,3-dithione with dimethoxycarbene, generated by thermolysis of 2,2-dimethoxy-5,5-dimethyl-2,5-dihydro-[l,3,4]oxadiazole, led to the formation of 4-isopropyl-idene-3,3-dimethyl-thietane-2-thione in trace amounts (2% yield), together with other products (Equation 23). 

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-dihydro-2,5(l//,4//)-pyrazinedionc (74) gave a separable 1 2 mixture of 6-isopropyl-5-methoxy- (72) and 3-isopropyl-5-methoxy-3,6-dihydro-2(l//)-pyrazinonc (73) [Me3OBF4 (1 mol), CH2C12, 20°C, N2, 6 h 60% (mixture)] or 2-isopropyl-3,6-dimethoxy-2,5-dihydro pyrazine (75) [Me3OBF4 (excess), CH2C12, 20°C, N2, 4 days 85%].1351... 

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 ... 

Dimethoxy-2-isopropyl-5-(2-methoxyca rbonyl-alkyl)-2,5-dihydro- E16d, 440 (Michael-Addition)... 

Hy droxy-ethyl)-5-i sopropyl-3,6-dimethoxy-2,5-dihydro- E21b, 1772 [2-H - 2-CH(OH)-Ar] 2-(l-Hydroxy-ethyl)-5-isopropyl-3,6-dimethoxy-3,6-dihydro- E21b, 1770 [H CH(OH)-CH3]... 

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. 

Difluor-l,2-dihydro-8-isobutyryl-4-isopropyl-5,7-dimethoxy-l-oxa-3-oxonia-2-borata-naphthalin (compound 6). 

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