Conversion of polyfunctional nitroalkanes into carbonyl compounds synthesis of the pheromone chalcogran and of key building blocks for the macrolides pyrenophorin and vermiculine

Abstract

Stiirting r r t m nitro:ilk;inc ;idducts of thc gcncral siructurc 3. sew-MI versions of the N d reaction are prformcd. Thc rcagoni comhiiiuticm HIOI KICOI turncd out to bc thc most uscful in libci-iiting thr c;irhonyl group bccausc of tcilrratiori of acid-scnsitive f i i t i~t i~~r~a l i t i c s .Other methods provide the acetiil 5. diketonc 7. y-hctoncs II and 9. o r the chlurinatcd niiro compound 13, rospc- In the preceding paper'' we reported on the eficient and very flexible synthesis of polyfunctional nitroalkanes 3. These were prepared by Michael addition of simple or already functionalized nitro compounds to the vinyl ketone 2, whose precursor is siloxycyclopropane 1. This protocol allows a very convenient creation of selectively functionalized carbon chains. Since the ultimate purpose of this concept is syntheses of building blocks for natural products, the transformation of the nitro group into a carbonyl or a hydroxy function is demanded. The distinction of these oxygen functions is an unalterable prerequisite in this process. 3Almost classical Nef conditions 5, employing sodium methoxide followed by application of concentrated sulfuric acid in methanol transform the nitroalkane 4 into the acetal 5 in high yield (Scheme I), whereas compound 6 gives the diketo ester 7 containing approximately 8 % of the methanol adduct of 2. Apparently, Nef reaction is fast and succeeded by acetalization in the case of the primary nitro compound 4. In contrast, retro-Michael reaction occurs to some extent with the secondary nitroalkane 6 providing 2 and its sub- sequent addition product with methanol. Protection of the keto function in 6 allows the C -NOz + C = 0 conversion without retro-Michael addition. However, the acetal moiety is cleaved by acid in the second step, and the yield of isolated 7 is only 54%.

Enantioselective Palladium-Catalyzed [3 + 2] Cycloadditions of Trimethylenemethane with Nitroalkenes

“…In contrast to Palomo’s report, however, we recovered not the ketone but gem -chloro-nitrocyclopentane 27 in reasonable yield as a single diastereomer. This unusual result has been observed previously, 17 and the structure of 27 has been unambiguously assigned by x-ray crystal analysis (Figure 3). The propensity for the peroxy acid to react not with the silyl nitronate, but with the chloride counterion demonstrated a need for a more reactive nitronate species.…”

Donor−Acceptor-Substituted Cyclopropane Derivatives and Their Application in Organic Synthesis

“…Parent vinylcyclopropane 16 and nitromethane provided Michael adduct 266 in high yield, which could be further substituted to diester 267 by a second 1,4-addition to methyl acrylate (Scheme ). , By Nef reaction intermediate 266 was also converted into acetal 268 . Similar transformations of other polyfunctionalized nitro compounds obtained via this route produced building blocks for prostaglandins or the antibiotic macrolide pyrenophorin (see section V.E, Scheme ) 73

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75

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“…Similar transformations of other polyfunctionalized nitro compounds obtained via this route produced building blocks for prostaglandins or the antibiotic macrolide pyrenophorin (see section V.E, Scheme 143 ). 128 By use of ammonium formate and Pd/C as catalyst, nitroalkane adducts of type 269 were efficiently converted into cyclic nitrones 270, which undergo 1,3dipolar cycloadditions to functionalized isoxazole The ultimate starting material in this sequence was siloxycyclopropane 16, which was allylated to provide compound 272 with the required dipolarophilic side chain. Whereas its ring cleavage combined with Michael addition of nitromethane proceeded without problems, nitrone 273 had to be generated by the less efficient zinc/ammonium chloride method (Scheme 77).…”

“…201 Siloxycyclopropane 16 and 1-nitropropane were combined to undergo the base-induced ring-opening Michael addition sequence (see Scheme 75 antibiotic macrolides such as pyrenophorin and vermiculin. 128 Enantiopure γ-keto ester 530 was most efficiently synthesized by trimethylsilyl chloride-assisted conjugate addition of in situ generated lower order cuprate 529 to enone 528 (Scheme 144). This compound was available in reasonable scale from the ethyl ester analogue of 16 (see Scheme 5) by standard treatment with fluoride.…”

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

“…40,42,43 Allylic acetals prepared from unsaturated carbonyls can be nitromercuriated; 44 nitromercurio ethers can be demercurated with NaBH 4 . 45,46 The b-nitro carbonyls and acetals can undergo modified Nef reactions with various bases or oxidants (DBU, 47 DBU/MCPBA, 48 49,50 borax/ KMnO 4 , 51 NaOH/NaNO 2 /AgNO 3 , 52 BuLi/MoOPH 53 ) as generally represented in Scheme 31 and generate b-dicarbonyl equivalent products. The Nef strategy has worked effectively on nitro acetals.…”