Vinyl conjugate addition

Conjugate addition of vinyllithium or a vinyl Grignard reagent to enones and subsequent oxidation afford the 1.4-diketone 16[25]. 4-Oxopentanals are synthesized from allylic alcohols by [3,3]sigmatropic rearrangement of their vinyl ethers and subsequent oxidation of the terminal double bond. Dihydrojasmone (18) was synthesized from allyl 2-octenyl ether (17) based on Claisen rearrangement and oxidation[25] (page 26). 

The primary disadvantage of the conjugate addition approach is the necessity of performing two chiral operations (resolution or asymmetric synthesis) ia order to obtain exclusively the stereochemicaHy desired end product. However, the advent of enzymatic resolutions and stereoselective reduciag agents has resulted ia new methods to efficiently produce chiral enones and CO-chain synthons, respectively (see Enzymes, industrial Enzymes in ORGANIC synthesis). Eor example, treatment of the racemic hydroxy enone (70) with commercially available porciae pancreatic Hpase (PPL) ia vinyl acetate gave a separable mixture of (5)-hydroxyenone (71) and (R)-acetate (72) with enantiomeric excess (ee) of 90% or better (204). 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

Synthetic polymers can be classified as either chain-growth polymen or step-growth polymers. Chain-growth polymers are prepared by chain-reaction polymerization of vinyl monomers in the presence of a radical, an anion, or a cation initiator. Radical polymerization is sometimes used, but alkenes such as 2-methylpropene that have electron-donating substituents on the double bond polymerize easily by a cationic route through carbocation intermediates. Similarly, monomers such as methyl -cyanoacrylate that have electron-withdrawing substituents on the double bond polymerize by an anionic, conjugate addition pathway. 

However, the configuration of the major isomer obtained in the conjugate addition to methyl ( )-3-[(35,)-3-tot-butoxycarbonyl-2,2-dimcthyl-4-oxazolidinyl]-2-propenoate (entry 3) did not depend on the cuprate type alkyl-, vinyl-, 2-methylpropenyl-, phenyl-, and benzvl-cuprates induced the same sense of asymmetry, although the absolute configuration was not determined5. Here also, the stereochemical outcome was not dependent upon the geometry of the double bond. 

Cory and Renneboog53 have devised an efficient bicycloannulation for the synthesis of tricyclo[3.2.1.02,7]octane-6-one (66) as shown in equation 63. The method involves three steps (1) the enolate undergoes an initial conjugate addition to phenyl vinyl sulfone, (2) the resulting sulfone-stabilized carbanion undergoes an intramolecular Michael addition to the enone, and (3) the resulting enolate displaces phenylsulfinyl moiety from the tricyclooctanone. The amount of HMPA (3 mol equivalents) is critical for effective cyclization of the enolate. 

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 stereoselective conjugate addition of lithium (Z)-dialkenylcuprates to vinyl sulfones gives (Z)-olefms in the range of 70-80% overall yield and no ( )-isomer is detected (equation 66)56. The degree of stereoselectivity is higher than 90%. 

TABLE 6. Conjugate addition of organometallic reagents to vinyl sulfones55... 

Deprotonation of the vinylic proton is a serious side-reaction in the conjugate addition of organometallic reagents to y-siloxy-a, /J-unsaturated sulfones (89)63b. The use of the... 

The conjugate addition of 103 to phenyl vinyl sulfone (53) proceeds under phase-transfer conditions. The yield of cyclopropanes in the following cyclization is low for synthetic purposes (equation 84)69. 

Recently, enantiomerically pure vinylic sulfoximines have been shown to undergo effective and highly stereocontrolled conjugate addition of hydrocarbon groups using organocopper reagents108. 

Given the above possible reaction mechanism, it is then intriguing to speculate that another approach to the same stereoselective reduction of a vinyl sulphone could be achieved by the use of a suitably sterically hindered organosilane, as outlined in equation (64). Such a reaction would provide an interesting test for the stereoelectronics of a conjugate addition reaction by a second-row heteroatom to a vinyl sulphone. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Thioazolium ions, as catalysts for conjugate addition of aldehydes, 59, 57 Thiobutyric acid, 55, 129, 131 Thioketals, conversion to vinyl sulfides,... 

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