1,4-Diazabicyclo octane reduction

An older paper <1971MI873> reported that ozonolysis of alkenes in the presence of tertiary amines resulted in the formation of aldehydes. A recent reinvestigation <20060L3199> has shown that amine oxides were responsible for this reductive ozonolysis . Indeed, pretreatment of the tertiary amines with ozone, giving rise to amine oxides, accounted for this phenomenon. A preparative method emerged, by treating the alkene (e.g., 1-decene) at 0 °C with a solution of 2% 03/02 in dichloromethane (2 equiv of ozone relative to the alkene) in the presence of an excess (about threefold molar excess) of A-methylmorpholine A-oxide, pyridine A-oxide, or l,4-diazabicyclo[2.2.2]octane A-oxide (DABCO A-oxide). Yields of aldehydes (nonanal in the above example) were 80-96%, and the excess of amine oxide ensured the absence of residual ozonide (Scheme 21). 

Further functionality (i.e., 4-oxo) has been introduced by the cyclization of a-allyloxy-carbonylnitrones, which have traditionally been problematic to obtain. Tamura and co-workers have reported that simple alkoxycarbonylnitrones (e.g., (243)) undergo transesterification and cyclization with various allylic alcohols in the presence of titanium isopropoxide (Scheme 43) <95T107, 95T119). Alternatively, allyl a-oximinocarboxylates (246) are converted in situ to nitrones (247) and further cyclized to the bicyclic heterocycles (248) (Scheme 44) <91T4495>. Tetrahydro-1 //-pyrrolo[3,4-c]isoxazoles (250) have been prepared by the condensation of C-acylnitrones with allyl amines <78AJC2013> further reduction of the bicycles (250) with sodium borohydride affords the 3-oxa-2,7-diazabicyclo[3.3.0]octane (251) (Scheme 45). 

Thus, numerous diazabicyclo[3.3.0]octanes ( pyrrolidinopyrrolidines ) were produced [101,102] and combined with various basic quinolone compounds, thereby resulting in quinolones which usually displayed powerful antibacterial activity [103,104]. However, these usually proved to be too toxic or displayed too great a reduction in their in vivo activity, and therefore were not investigated any further (cf. Fig. 14.7 X and R represent various radicals). 

In a similar reaction, the reduction of 3,7-dimethyl-l,5-diazabicyclo[3.3.0]-octane-2,6-dione (VIII/127) to the cyclooctane derivative VIII/128 (Scheme VIII/23) was nearly quantitative. 

One such epidioxypiperazinedione has been reduced to a regular pyrazine. Thus l,4-dibenzyl-2,3-dioxa-5,7-diazabicyclo[2.2.2]octane-6,8-dione (86) underwent reduction by sodium borohydride in ethanol at 20°C during 1 h to afford 3,6-dibenzyl-3,6-dihydroxy-3,6-dihydro-2,5( l//, 4//)-pyrazincdione (86a) in 65% yield, confirmed in structure by dehydration to 3,6-dibenzylidene-3,6-dihydro-2,5(1 H, 4//)-pyrazincdionc (86b).5... 

CarbocycUc Steroids.— The Torgov synthesis continues to exhibit its great versatility and was recently employed in the first synthesis of B-homo-oestrone. Condensation of the vinyl alcohol (407) and 2-methy 1-cyclopentane-l,3-dione in the presence of l,4-diazabicyclo[2,2 ]octane and cyclisation with toluene-p-sulphonic acid gave the B-homo-oestrapentaene (409) in 33 % overall yield from 3-methoxybenzosuberone. A three-stage reduction by sodium borohydride, catalytic hydrogenation, and lithium-ammonia afforded 3-methoxy-B-homo-... 

Preparation. From NaAlH2Et2 and RjB in the presence of 1,4-diazabicyclo-[2.2.2]octane. Such reagents with bulky alkyl groups exhibit high stereoselectivities in reduction reactions. 

The starting material for iloprost is the enantiomerically pure Corey lactone, which is treated with the lithium salt of ethyl acetate. After oxidation, treatment with l,5-diazabicyclo[4.3.0]non-5-ene (DBN) leads to an exceptionally interesting rearrangement. Presumed cleavage of the cyclic ether generates an enolate, which adds to the cyclopentenone in a Michael reaction. Decarbethoxylation is achieved with l,5-diazabicyclo[2.2.2]octane (DABCO), and the w-chain is constructed under Horner-Wadsworth-Emmons conditions. The subsequent reduction leads to a mixture of allyl alcohols, which can be purified by chromatography, and the alcohol from the less polar product then be released by trans-esterification. Both alcohol functions are then protected as THP-ethers. The... 

In a similar manner, simple Baylis-Hillman alcohols 62 were transformed into P,y-disubstituted-a-methylene-y-lactams 29b (Scheme 4.16) [48]. The sequential treatment of alcohols 62 with HBr, DABCO (l,4-diazabicyclo(2.2.2]octane), and a nitroalkane 51 afforded the requisite 2-methylene-4-nitroalkanoates 63 as two diastereoisomers in a 1 1 ratio. Subsequent standard transformations involving reduction of the nitro group and lactamization gave the final products 29b as mixtures of two diastereoisomers with the ratio originating from the substitution... 

PUR foams. When it is reacted with ethylene oxide, there is block copolymerization at the end groups. Commercial testing of Laprol 3503 has shown that in the production of molded PUR articles there is a reduction in their mass without reduction in strength-related properties, resulting in reductions in the consumption of raw material and the reject rate, and accordingly a reduction in the labor outlay in repair of the articles. Because of the relatively high chemical activity of Laprol 3503, it is possible to dispense with the expensive catalyst DABCO (1,4-diazabicyclo-2,2,2-octane). 

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