Y-alkoxy-a,p-unsaturated

The azomethine yhde derived from 79 has also been used in reactions with chiral ( )-y-alkoxy-a,p-unsaturated esters 80 (Scheme 12.27). The corresponding tetra-substituted pyrrolidines 81 were obtained with complete regiocontrol in fair to excellent de (125). 

Lithium divinyl cuprates. The addition of. inylic cuprates to chiral -y-alkoxy-a,p-unsaturated ketones and esters proceeds with high diastercoselectivity the major product is that in which the vinyl group is anti to the ally lie alkoxyl group. The geometry of the unsaturated system docs not affect the stcrcocheiiiistry of the addition. 

Figure 10.25 Twenty-nine specific toxicophores for mutagenicity as identified by Kazius el al. (Kazius, J-, et al. Derivation and validation of toxicophores for mutagenicity prediction. J. Med. Chem. 2005, 48, 312-320.) (A) Specific aromatic nitro, (B) specific aromatic amine, (C) aromatic nitroso, (D) alkyl nitrite, (E) nitrosamine, (F) epoxide, (G) aziridine, (H) azide, (I) diazo, (J) triazene, (K) aromatic azo, (L) unsubstituted heteroatom-bonded heteroatom, (M) aryl hydroxylamine, (N) alkyl halide, (O) acyl halide, (P) N- or 5-mustard, (Q) polycyclic aromatics, (R) bay-region, (S) K-region, (T) sulphonate-bonded C, (U) unsaturated aldehyde, (V) alkyl A-nitro, (W) diazonium, (X) p-propiolactone, (Y) unsubstituted a,p unsaturated alkoxy, (Z) l-aryl-2-monoalkyl hydrazine, (AA) aromatic methylamine, (AB) aryl hydroxylamine ester, and (AC) polycyclic planar system.

Scheme 7.70 Proposed mechanism for the multi-step one-pot synthesis of y-alkoxy or y-hydroxy a,p-unsaturated esters and nitriles...

The alkoxy radicals so formed are the precursors of a, P-unsaturated ketones, aldehydes, carboxylic acids and alcohols. Saturation reactions, Nor-rish type I reactions of ketonic compounds and oxidation of aldehydic species occur under irradiation. This finally leads to the formation of saturated carboxylic acids as the main oxidation products accompanied by esters, y-lactones, peresters, anhydrides, alcohols and ether bridges. 

Hydroxybenziodoxole 104 can be readily converted into its acetoxy derivative, l-acetoxy-1,2-benziodoxole-3(l//)-one (88, 2X = O, Y = OAc), by heating 104 with acetic anhydride and the acetoxy derivative can be further converted into the alkoxy derivatives by treatment with an appropriate alcohol [280], The tetrabutylanmionium salt of hydroxybenziodoxole 104 has been prepared by the reaction of hydroxybenziodoxole with tetrabutylammonium fluoride in THF it is a mild oxidant that is useful for the preparation of epoxides from a,p-unsaturated carbonyl compounds [281], l-Hydroxy-l,2-benziodoxole-3(l//)-one and l-acetoxy-l,2-benziodoxole-3(l//)-one have found wide application as starting compounds for the synthesis of various benziodoxole-based hypervalent iodine reagents by ligand exchange on iodine [239]. 

Scheme 18.17 Rearrangement of y-alkoxy allylic sulfoxides to a,p-unsaturated aldehydes as applied to prostaglandin synthesis.

High regioselectivity has been observed for addition of silyl enol ethers to a,p-unsaturated aldehydes and ketones, promoted by lithium perchlorate in diethyl ether. Potassium enolates of acyclic y-alkoxy-a-methyl pentanoates can be alkylated with allylic and benzylic halides with high 2,3-syn selectivity. The results have been rationalized in terms of non-chelated (for potassium enolates) and chelated (for lithium enolates) transition states. 

Shin, C., Y. Sato, and J. Yoshimura a,P-Unsaturated Carboxylic Acid Derivatives. XI. Convenient Synthesis of tert.-Butyl 2-Alkoxy- and Hydroxy-2-acetylamino-3-mono- or 3,3-dihaloalkanoates. Bull. Chem. Soc. Japan 49, 1909 (1976). 

In 1993, Tiecco et al. reported a similar reaction for p,y-unsaturated esters, amides or nitriles with 10 mol% of diphenyl diselenide (449) and an excess of ammonium persulfate in alcohols or water to afford the y-alkoxy or y-hydroxy a,ji-unsaturated derivatives in good yields (Table 7.32) [311],... 

Alkoxy-2,5-dihydrofurans were oxidatively cleaved to p-alkoxy-substituted a, 3-unsaturated y-ketoaldehydes by using DDQ, as shown below. Presumably, the reaction occurred via the corresponding 3-alkoxyfuran as a transient intermediate <07AGE1634>. However, (5-alkoxybutenolides were obtained from these substrates under Mn(III)-catalyzed ally lie oxidation conditions <07SL1294>. 

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

We knew that a-alkoxy-P,y-unsaturated aldehydes were not suitable for Evans condensations... 

We could prepare a-alkoxy-y-phenylselenenyl aldehydes as "stable" equivalents of a-alkoxy-P,y-unsaturated aldehydes but their reaction with boron enolates did not lead to the expected condensation products, probably due to inadequate work up conditions. 

Alternatively, we surmised that the lactone 14 could be converted to Weinreb amide 40, which provided additional options for generation of the homoallylic alcohol 42. For example, through the influence of an a-alkoxy group, homoallylic alcohol 42 could be obtained by either a chelation-controlled reduction of p,y-unsaturated ketone 41 or a non-chelation-controlled allylation of 13 (Scheme 14). Thus, elaboration of lactone 35 into amide 40 began by treatment of 35 with N,0-hydroxylamine hydrochloride in the presence of trimethylaluminum to give the amide 39 in 93% yield. Further, protection of the revealed... 

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