Conjugate addition procedures

Cycloalkenones are ubiquitous as reactive intermediates and bioactive materials. Modification of a simple cycloalkenone by addition of a carbon substituent at the o-position should be a useful transformation, but one that is not readily accomplished by conventional enone chemistry. a-Substituted cycloalkenones could of themselves be of interest, but perhaps, of more general importance would be their use as intermediates for the production of substituted cycloalkanones or a, 5-disubstituted cycloalkanones by a subsequent conjugate addition procedure.2 These strategies avoid many of the limitations attendant to the trapping of enolates with carbon electrophiles. The method of Kim involving treatment of enones with the combination of a dimethyl acetal, pyridine and trimethylsilyl triflates results in a-(1-methoxyalkyljenones.3 The metallation of a-bromoenones masked as ketals for [Pg.184]

This amphiphilic conjugate alkylation system has been improved to a synthetically useful level by the development of aluminum tris(2,6-diphenylphenoxide) (ATPH) as a highly efficient carbonyl stabilizer, thereby achieving a practical conjugate addition procedure. 

The lithio cuprate conjugate-addition procedure for the preparation of 1-PGEi methyl ester has been studied in considerable detail by Sih, who introduced this useful process to prostaglandin synthesis (3T). 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

A result equivalent to an allylic substitution reaction with a chiral leaving group can also be achieved by a two-step procedure involving a conjugate addition reaction and a subsequent elimination reaction, as demonstrated by Tamura et al., wbo studied the reaction shown in Scheme 8.15 [27]. 

Posner recently reported a very simple and fast way to activate epoxides towards nucleophilic opening by ketone lithium enolate anions by use of BF3 Et20 (1 equiv.) [73]. The application of this procedure to the nucleophilic opening of propene oxide with the lithium enolate of 2-cycloheptanone, obtained by the conjugate addition of trimethylstannyllithium to 2-cycloheptenone, afforded the stan-... 

Butvlcyclohexanone by Conjugate Addition of a Chiral Hetcrocuprate Derived from C to 2-Cyclo-hexenone (Table 4, Entry 9) Typical Procedure ... 

An example for synthesis of the chiral [l-keto ester 69 is illustrated in equation 64. It involves conjugate addition of the dipotassium / -keto ester 68 to vinyl sulfone 67 followed by in situ quenching with allyl bromide54. The method provides a new procedure to sevenring annulation product 70 that is a potential precursor for (l)-(-)-cytochalasin C. 

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

A particularly important example of the intramolecular aldol reaction is the Robinson annulation, a procedure that constructs a new six-membered ring from a ketone.171 The reaction sequence starts with conjugate addition of the enolate to methyl... 

Suggest starting materials and reaction conditions suitable for obtaining each of the following compounds by a procedure involving conjugate addition. 

Entries 5 to 9 illustrate some of the modified reagents and catalytic procedures. Entry 5 uses a phosphine-stabilized reagent, whereas Entry 6 includes BF3. Entry 7 involves use of TMS-C1. Entries 8 and 9 involve cyanocuprates. In Entry 9, the furan ring is closed by a Mukaiyama-aldol reaction subsequent to the conjugate addition (Section 2.1.4). 

---