Enones alkylation with

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

Recently, Maruoka described the novel dual function catalyst 26 bearing hydroxyl groups which were incorporated to allow hydrogen bonding to the enolate intermediate. Indeed, 26 was found to catalyze enone epoxidation with 89-99% tt [67]. Interestingly - and unlike some other systems - alkyl substitution is tolerated (Scheme 12.14). 

Simple diastereoselectivities are observed in the reaction of cyclo-alkenones with cyclic alkenes, e.g., cyclopentene, wherein the transoid tricycle is formed preferentially. Whereas cyclopent-2-enone (7) affords 36 selectively, the more flexible cyclohex-2-enone (8) gives a 3 1 mixture of diastereoisomers 37 and 38 [7,61]. A stereogenic center in the cycloalkenone also has a strong impact on the product ratio as shown for the reactions of 4-alkylcyclohex-2-enones 39 and 40 with acyclic alkenes wherein the major diastereoisomer formed is the one in which the enone-alkyl group is trans to the new ring forming C-C bonds, i.e., 41t and 42t, respectively (Sch. 12) [62,63]. Cycloadducts 42 have been further converted to the pheromone periplanone-B. 

Fig (16) The enone (131), prepared from (130) is alkylated with iodide (133) to obtain the product (134). It reacts with trimethylsilyl cyanide and zinc iodide. The resulting product (135) is converted to tricyclic compound (136) by heating with hydrochloric acid and ethanol. 

An alternative disconnection of the alkoxide requires the addition of a silyllithium reagent to an enone. Addition of stoichiometric base to the alcohol 51 produces an alkoxide 52, but no evidence of Brook rearrangement to generate 53 was found on protonation of the product. However, alkoxide 52 must exist in equilibrium with some of the organolithium 53, since alkylation with a soft electrophile (Mel) produced 54.41 The equilibrium concentration of the organolithium 53 is lessened in this case by the impossibility of O-Li coordination. 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

One of the syntheses mentioned there started with 3-pyrazolidinone 236, which was protected as the benzyloxycarbonyl derivative 237 in order to obtain selective N-alkylation at position 8 yielding compound 238 after removal of the protecting group. Addition of the resulting amine 238 to l-octyne-3-one 239 formed the enone 240 with the complete diazaprostanoid skeleton. Katalytic... 

Another route to (+)-19-nortestosterone (73) started firom 2-methyl-l,3 cyclopentanedione (74). The asymmetric aldol condensation of the Michael adduct using L-phenylalanine produced the opticaUy active enone (75). The PdCh-catalyzed oxidation yielded crystalline trione (76) in 77% ee, which was recrystallized as an optically pure form. Reduction of the double bond and aldol condensation afforded the desired cd tratu-fused ketone (77). The construction of the A-ring was carried out by alkylation with... 

Reactions of the Bislactim Ether Cuprate. The lithiated bislactim ether can be converted to an azaenolate cuprate by treatment with CuBr SMe2 (see Copper(I) Bromide)fi Conjugate addition of the cuprate to enones (eq 3) and dienones, or alkylation with base labile electrophiles like ethyl 3-bromopropionate, proceeds with high trans diastereoselectivity. Hydrolysis of the Michael... 

The ultimate in the three-component coupling approach to prostaglandins has now been achieved by Noyori (48). As illustrated in Fig. 15, the cuprate derived from iodide [82] was added to enone [80] in the usual fashion. Then, after addition of hexamethylphosphoramide, triphenyltin chloride was used to effect enolate interchange. As opposed to lithium (or copper) enolates, the tin enolate is cleanly alkylated with allylic iodide [81]. The protected PGE2 [83] was obtained in 78% yield. Two-step deprotection to PGEj was straightforward. 

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