Unsaturated, Acyclic Compounds

Alditol derivatives having terminal double bonds have frequently been prepared by treatment of vicinal, primary-secondary disul- 

Further examples of l-phenylazo-l,2-unsaturated alditols derived by acetylation of aldose phenylhydrazones have been described,172 and a dimer, namely, l,2-bis(penta-0-acetyl-D-gluconoyl)ethylene (92), formed by way of a carbene intermediate, was reported to be 

Finally, further examples of unsaturated 1-nitroalditols have been described, and have been utilized in standard syntheses of 2-deoxy-aldoses by this means, 2-deoxy-D-rtho-hexose,174 2-deoxy-D-manno-heptose,175 2-deoxy-D-gaiacto-heptose,176 and 2,6-dideoxy-L-manno-heptose177 have been prepared. The reaction of ammonia with 3,4,5,6-tetra-0-acetyl-l,2-dideoxy-l-nitro-L-arabino-hex-l-enitol has been further examined, and found to proceed stereospecifically to give 

---

Diastereomers are also encountered in unsaturated acyclic compounds. When two C atoms are joined together by a double bond, all the remaining four single bonds to the two C atoms lie in the same plane as the C=C bond. If each of these two carbon atoms is bonded to a H atom and a hydrocarbon (alkyl) chain, the alkyl chains can be either on the same side of the C=C bond as each other or on opposite sides, and the resulting diastereomers (which used to be known as geometric isomers), shown in Fig. 2.2b, are termed cis and tram, respectively. Again, these diastereomers have different physical properties (see also Box 2.3). Optical isomerism is not possible about a C=C bond (the mirror images are superimposable). 

In the main, the physical and chemical properties of saturated and partially unsaturated alicyclic compounds closely resemble those of the analogous acyclic compounds formally derived by cleavage of the carbon ring at a point remote from any functionality. Relatively small, but often significant, differences in properties arise from conformational effects, and from strain effects in small rings, and these differences can be striking in properties which are particularly sensitive to molecular shape. 

Saito et al. (32,121) developed a variety of tartaric acid derivatives, including Ci-symmetric chiral alkenes such as 76. The 1,3-dipolar cycloaddition between 76 and 77 gave primarily endo-1%. (Scheme 12.26) The diastereofacial selectivity of the reaction is excellent, as endo-1% is obtained with >98% de. Other cyclic and acyclic nitrones have been employed in reactions with 76, and in all cases, moderate to excellent endo/exo-selectivities and excellent diastereofacial selectiv-ities were obtained (32,121). Three other research groups have applied various y-hydroxylated ot,p-unsaturated carbonyl compounds in related reactions with nitrones (122-124). However, the selectivities were somewhat lower than those obtained by Saito and et al. (32,121). 

C derivatives embracing a variety of substituted phenyl compounds and such unsaturated acyclic groups as allyl and vinyl.40... 

Aromatic aldehydes react very easily with tetramic acid under acidic conditions to give 3-benzylidene compounds (41). The yields are moderate, because often there are subsequent reactions. As a,/3-unsaturated carbonyl compounds, (41) react in a Michael addition with excess tetramic acid to form (67), but it can also react with other acyclic and cyclic 1,3-dicarbonyl compounds. In these reactions the aryl substituents may vary over a wide range. Thus, (67) and (68) can be cyclized with ammonium acetate to afford pharmacologically interesting compounds (70) and (71) (90TH1). The latter are dihydropyridines. Curiously, (69) does not cyclize under these conditions. (See Fig. 32.)... 

Although acyclic a,/ -unsaturated carbonyl compounds usually only undergo cis/trans-isomerization, irradiation of methyl 2,4-dioxopentanoate (15) in a mixture of benzene and cyclohexane affords a crystalline head-to-hcad cyclodimer 16.24... 

Besides acyclic unsaturated carbonyl compounds, their alicyclic analogues may be used, leading to fused dihydropyran derivatives. Cyclic vinyl ethers have also been utilized in the process. 

Since early investigations about the asymmetric addition of diethyl sodiomalonate to optically active vinylic sulfoxides,100-101 Posner and his coworkers102-117 have developed a highly useful methodology based on the conjugate addition of carbon nucleophiles to homochiral a-arylsulfinyl-a,(J-unsaturated carbonyl compounds. While acyclic derivatives still lead only to moderate results,103 the strength of this method is for cyclic systems. For example, the 2-sulfinyl-2-cycloalkenones (94) and (95), the 2-sulfinyl-2-alkenolides (96) and (97), as well as their respective enantiomers are excellent substrates. All these compounds are quite readily accessible in enantiomeric purities of >98% and are configurationally stable, at least for several months at 0 C. 

Several recent reviews have included specific types of electrophilic cyclofunctionalization reactions.1 Important areas covered in these reviews are halolactonization u cyclofunctionalization of unsaturated hydroxy compounds to form tetrahydrofurans and tetrahydropyrans lb cyclofunctionalization of unsaturated amino compounds lc cyclofunctionalization of unsaturated sulfur and phosphorus compounds ld lf electrophilic heterocyclization of unconjugated dienes 1 synthesis of y-butyrolactones 1 h synthesis of functionalized dihydro- and tetrahydro-furans lj cyclofunctionalization using selenium reagents lk lm stereocontrol in synthesis of acyclic systems 1" stereoselectivity in cyclofunctionalizations lP and cyclofunctionalizations in the synthesis of a-methylenelactones.lq Previous reference works have also addressed this topic.2... 

On the basis of the reaction of conjugated dienes with unsaturated halides in the presence of external nucleophiles, an elegant intramolecular version leading to a-alkylidene-y-lactams, has been developed (Scheme 8.19). Starting with an aryl halide, the regioselective insertion of an arylpalladium halide to the triple bond of acyclic compound 42 gives the c-vinylpalladium intermediate 43. Subsequent intramolecular carbopalladation of the diene affords a re-allyl palladium intermediate... 

Cheap and readily available L-proline has been used numerous times for the intermediate and reversible generation of chiral iminium ions from a,/ -unsaturated carbonyl compounds. For example, Yamaguchi et al. reported in 1993 that the rubidium salt of L-proline catalyzes the addition of di-iso-propyl malonate to the acyclic Michael acceptors 40a-c (Scheme 4.13), with enantiomeric excesses as high as 77% [22], With 2-cycloheptenone and 2-cyclohexenone as substrates ca 90% yield and ee of 59% and 49% were obtained. Later the enantioselectivity of this process was increased to a maximum of 88% ee in the addition of di-tert-butyl malonate to the E-pentenone 40a in the presence of 20 mol% Rb-L-prolinate and 20 mol% CsF [23], Taguchi and Kawara employed the L-proline-derived ammonium salts 41a and... 

Essentially, two types of unsaturated bifunctional compound display the capability of being condensed in high yield, via a transition metal-catalysed carbon-carbon coupling reaction, into their requisite generic high molecular weight polymers plus a small molecule non-conjugated acyclic dialkenes and haloaromatic derivatives. 

The 1,2-addition of allyl iodide to cyclic and acyclic a,/ -unsaturated carbonyl compounds has been achieved by using indium and indium trichloride. The reactivities of a,/3-unsaturated carbonyl compounds depend upon their structure. The reaction of ketones smoothly undergoes in THF or DMF. In the case of cyclic ketones, however, the solvent plays a crucial role, where much improved yields have been obtained in DMF than in THF (Equation (49)).236 Indium-mediated 1,2-allylation of /3-bromoacrolein produces homoallylic alcohol derivatives (Equation (50)), which can be transformed to cyclopentanones by a Pd-catalyzed cyclization.237,238... 

---