Lithium with acyclic aldehydes

In order to reverse the diastereoselectivity in the aldol reaction, the Lewis acid-catalyzed silyl enol ether addition (73) (Mukaiyama aldol reaction) was examined. Since the Mukaiyama aldol reaction is assumed to be proceeded via an acyclic transition state, a chelation controled aldol reaction of the a-alkoxy aldehyde should be possible (74). In the presence of TiCU, the silyl enol ether derived from 14 was reacted with aldehyde 13, followed by desilylation to afford the desired anti-Felkin product 122a as a single adduct (Scheme 21). Based on precedents for chelation-controlled Mukaiyama aldol reaction (74), the exceptional high selectivity in this reaction would be accounted for by chelation of TiCl4 with the C23-methoxy group of the aldehyde 13 (eq. 13). On the other hand, when the lithium enolate derived from 14 was treated with the aldehyde 13, followed by desilylation, it gave a 1 4 ratio of the two epimers in favour of the undesired (22S)-aldol product... 

Homologation of aldehydes can be achieved by reaction of the anion (26) with the aldehyde, metallating with BuLi, and hydrolysing the intermediate thus obtained. " The alkenyl-lithiums (27) and (28) provide routes to functionalized carbonyl compounds, both cyclic and acyclic, on reaction with a variety of conventional electrophiles. By employing bulky substituents at the carbonyl group of the enones (29a and b), a -activity is enforced. Lithium amides may be carbonylated to give the corresponding carbamoyl-lithiums (30), which are useful acyl anion equivalents. ... 

Diastereoselectivity in the aldol and the conjugate additions of 2 -hydroxy-1,T-binaphthyl ester enolates with a variety of carbonyl electrophiles has also been explored the tendency of the ester enolates, generated by BuLi, to react with aldehydes to give threo products preferentially with high diastereoselectivity has been interpreted in terms of an acyclic transition state of chelated lithium enolate involving the aldehyde carbonyl and the 2 -hydroxy group. 

A number of other acyclic Z and E lithium enolates were quenched similarly. In all cases the stereochemistry at the enol double bond was retained, as shown by subsequent conversion into the corresponding silyl enol ether. Upon reacting the titanium enolates with aldehydes, very clean aldol addition occured (>90% conversion at —78 °C). Generally, erythro-selectivity was observed irrespective of the geometry of the enolate. Equations 64 and 65 are typical25). 

Complexation of an acyclic a-lithio selenide with a chiral diamine led to diastereoisomeric complexed lithium intermediates which reacted with aldehydes more rapidly than the uncomplexed forms [201 (Scheme 20). They were charac-... 

Synthesis of the acyclic portion began, as in the previous synthesis, with enantiomerically pure citronellol (25). Protection of the alcohol as the benzyl ether and oxidative cleavage of the olefin to the aldehyde gave 26 (85%). Chain extension via the masked acyl anion equivalent 27, alcohol protection, and concomitant -elimination and isomerization of the allene to die alkyne with butyl lithium gave 28. The resulting protected ketone must now be converted to the P-alcohol required for the completion of the synthesis. Thus hydrolysis to die ketone followed by enantioselective reduction with (—)-N-methylephedrine-... 

The paper reports preparation of two new copper hydride complexes. The lithium complex (1) is prepared from CuBr and 2 equiv. of lithium trimethoxy-aluminum hydride (cf. 5, 168) the sodium complex (2) is prepared from CuBr and 1 equiv. of sodium bis(2-methoxyethoxy)aluminum hydride. Both complexes are useful for selective reduction of the double bond of conjugated cnones 1 is more efficient for reduction of cyclohexenones and 2 is more efficient for reduction of acyclic enones. Aldehydes, ketones, and halides are also reduced nitrile and ester units are inert. The effective stoichiometry of both reagents is consistent with the structures LiCuHj and NaCuHs, but complex 1 is clearly different from a reagent assigned the structure LiCuHa by Ashby et al. ... 

A new method for the conversion of aldopyranosides to 5-thioaldopyranosides is exemplified in Scheme 3 the isomeric acyclic intermediates, e.g. compound 33, could be separated, inverted at C-5 and cyclized stereoselectively, thus offering access to several different products. 5-Thio-D-arabinose (34) has been synthesized from D-arabinose in six standard reaction steps. Synthesis of 5-thio-L-fucopyranose, as the tetraacetate 35, from D-arabinose required chain-extension at the non reducing end which was achieved by diastereoselective reaction of aldehyde 36 with methyl lithium the D-aftro-product 37 was then treated sequentially with tosyl chloride and potassium thioacetate. A number of aryl a-5-thiofucosides, as well as p-nitrophenyl a-l,5-dithiofucoside, were prepared from 1-acetate 35 directly or via a trichloroacetimidate. These compounds were used to demonstrate the importance of sulfur in the ring and oxygen at the... 

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. 

In addition to this example of acyclic stereocontrol, the concept has also been applied to the cyclic chiral lithium enolate 101 this also resulted in high diastereoselectivity when the enantiomeric enolates were combined with the chiral aldehydes 102. As demonstrated by Eqs. (45) and (46), here again the stereochemical outcome is determined by the configuration of the enolate 101 [176]. 

Prepa ation.—Dimethylsilyl enol ethers of aldehydes and ketones may be prepared by irradiating the carbonyl compounds in the presence of dodecamethyl-cyclohexasilane (MeaSije/ Highly stereoselective formylation of (Z)-enol silyl ethers has been achieved on treatment of acyclic ketones with ethyl tri-methylsilylacetate and tetrabutylammonium fluoride on the other hand lithiation of pentan-3-one with lithium 2,2,6,6-tetramethylpiperidide followed by chloro-trimethylsilane gave mainly (84%) the ( )-enol silyl ether... 

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