Unsaturated diastereoselective additions

The diastereoselective addition of [(S)-3-alkoxy-l-octenyl]lithium to an enantiomerically pure cyclic y-(rer/-butyldimethylsilyloxy)-o(,/S-unsaturated sulfone was employed in the synthesis of ( )-prostaglandin E219, with addition occurring exclusively anti to the sterically demand-... 

Variable levels of asymmetric induction or diastereoselectivity have been found with additions of or-ganometallics to a,0-unsaturated chiral amides (chiral auxiliary). For example, as shown in Scheme 26, Mukaiyama reports that the diastereoselective addition of Grignard reagents to -substituted a,p-un-... 

In contrast, few examples of conjugate additions of nonallylic a-sulfinyl (or a-sulfonyl) carbanions have been reported (for allylic oc-sulfinyl carbanion additions, see Section 1.2.2.5.1). Notable is the dia-stereoselective addition of alkyl f-butyl sulfoxides (245) to a,(3-unsaturated esters (equation 20)187 which is complementary to the diastereoselective addition of enolates to 3-substituted-a,f3-unsaturated sulfoxides (equation 20). 

In the pioneering work by Wilcox and Gaudino, a straightforward route to the carbocyclic analogue of D-fructofuranose, 64, and its 6-phosphate derivative was delineated [14a,b]. As shown in Scheme 9, the first move consisted of Wittig olefination of benzyl-protected arabinose 60 with carboxy-tert-butylmethylene triphenyl phosphorane to deliver unsaturated ester 61, which was then cleverly elaborated into dibromide 62 via a reaction cascade encompassing Swem oxidation of the secondary OH, ester hydrolysis, diastereoselective addition of dibromomethyl lithium, and carboxylic acid methylation. 

In a similar fashion, diastereoselective addition of the vinylcuprate 103 to the glyceraldehyde-derived enone 102 was used for the construction of the precursor 104 of iso[7]-levuglandin D2.92 Besides enones and enoates, heteroatom-substituted nitroolefins and a,/3-unsaturated phosphine oxides also participate in diastereoselective copper-mediated 1,4-addition reactions.93,93 1,938... 

The stereochemistry of conjugate addition of organomagnesium compounds to a,[3-unsaturated ketones is governed by similar considerations to those governing addition to saturated ketones recent examples include diastereoselective additions to both acyclic (6) [77] and cyclic [78] (7) enones. 

Piperidine and benzylamine have been utilized in diastereoselective addition reactions to other a,/ -unsaturated vinyl sulfoxides bearing the R absolute configuration92,93 at sulfur. A conjugate addition of piperidine to (f )-l-methyl-4-[(Z)-l-propenylsulfinyl]benzene (20) in a polar solvent such as methanol gives an 83 17 (21A/21B) diastereomeric mixture of adducts94,95. 

Diastereoselective addition of cuprate reagents to unsaturated oxazolidines and subsequent hydrolysis affords 3-substituted aldehydes with up to 81% ee (eq 11). ... 

Incorporation of an auxiliary into a cyclic system has been used for the diastereoselective addition of cuprates to unsaturated 6-membered ring dioxinones, which are perhaps less important for their synthetic potential than for the mechanistic insight they provide. The dioxinones shown in Scheme 4.12a were obtained from / -3-hydroxybutanoic acid using the self-regeneration of chirality centers concept discussed in Chapter 3 (c/., Scheme 3.9 and 3.10). After the addition, hydrolytic removal of the achiral auxiliary (pivaldehyde) liberates a 3-alkyl-3-hydroxybutyrate that is essentially enantiomerically pure [134]. 

As previously discussed, 2 -i- 2 photocycloaddition can be stereoselective when carried out with rigid starting materials. When unsaturated lactam 178, prepared in a few steps from levulinic acid and (S)-( -f )-valinol, was subjected to photocycloaddition with ethylene, a very diastereoselective addition (de = 85%) takes place [152] (Scheme 29). Acidic methanolysis produces the corresponding esters and recovered valinol. Preferential formation of 179 involves an attack of ethylene from the convex side of the molecule. 

The role of the imidazolidinone catalyst 100 employed is depicted in Scheme 6.13. In the proposed cycle, the nucleophile (Nu) is added over the first formed a,p-unsaturated iminium ion 102. After a fast hydrolysis, adduct 104 and catalyst 100 are released. The adduct 104 would then enter in the second catalytic cycle to form the active enamine 105, which could trap the electrophile (E) present in the reaction in a highly diastereoselective addition. 

Das, S., Kumar, J.S.D., Shivaramayya, K., and George, M.V., Formation of lactams via photoelectron-transfer catalyzed reactions of N-aUylamines with a,P-unsaturated esters. Tetrahedron, 52,3425,1996. (a) Bertrand, S., Glapski, C, Hoffmann, N., and Pete, J-P., Highly efficient photochemical addition of tertiary amines to electron deficient alkenes. Diastereoselective addition to (5R)-5-menthyloxy-2(5ff]-furanone. Tetrahedron Lett., 40, 3169, 1999 (b) Bertrand, S., Hoflfrnann, N., and Pete, J-P., Stereoselective radical addition of tertiary amines to (5R)-5-menthyloxy-2[5H]-furanone application to the enantioselective synthesis of (-)-isoretronecanol and (-l-)-labumine. Tetrahedron Lett., 40,3173,1999 (c) Farrant, E. and Mann, J., Novel synthesis of the indoUzidine alkaloid skeleton with appropriate functionality and stereochemistry for use as a chiral scaffold, /. Chem. Soc., Perkin Trans. 1,1083,1997. 

When having an Q ,/3-unsaturated carbonyl moiety, 2(5/7)-furanones are capable of undergoing 1,4-Michael-type additions. It was found that 1,4-addition reactions of thiophenols to the furanones 168,170, and 172 take place at room temperature in the presence of triethylamine to give a quantitative yield of the adducts 169, 171, and 173. Complete diastereoselective Michael-type addition occurred in all cases (Scheme 48) (88T7213). 

The stereochemical outcome of the Michael addition reaction with substituted starting materials depends on the geometry of the a ,/3-unsaturated carbonyl compound as well as the enolate geometry a stereoselective synthesis is possible. " Diastereoselectivity can be achieved if both reactants contain a stereogenic center. The relations are similar to the aldol reaction, and for... 

Corey used a chiral bromoborane 75 (1.1 equiv.) to promote the addition of tert-butyl bromoacetate (76) to aromatic, aliphatic, and a,P-unsaturated aldehydes to give the halo alcohols 77 with high enantio- and diastereoselectivities (Table 1.10) [35]. 

The titaniated (25)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazines derived from cyclo(L-Val, Gly) or cyclo(L-Val, Ala) (1, R1 = H, CH3) react with a,/I-unsaturatcd aldehydes exclusively by 1.2-addition (cf. nearly exclusive 1,4-addition of ,//-unsaturated ketones with cuprate complexes of 2,5-dialkoxy-3,6-dihydropyrazines, see Section D. 1.5.2.3.1.4.) in a highly diastereoselective mode to give virtually only the (l S,2R)-diastereoniers 2 ". In reactions with the corresponding lithiated pyrazines both regioselectivity and diastereofacial differentiation at C-2 are also remarkably high (dc 95 %), but the diastereomeric excess at C-l is substantially smaller (30 50%) ... 

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