P-Unsaturated Systems

Vinyllithium [917-57-7] can be formed direcdy from vinyl chloride by means of a lithium [7439-93-2] dispersion containing 2 wt % sodium [7440-23-5] at 0—10°C. This compound is a reactive intermediate for the formation of vinyl alcohols from aldehydes, vinyl ketones from organic acids, vinyl sulfides from disulfides, and monosubstituted alkenes from organic halides. It can also be converted to vinylcopper [37616-22-1] or divinylcopper lithium [22903-99-7], which can then be used to introduce a vinyl group stereoselectively into a variety of a, P-unsaturated systems (26), or simply add a vinyl group to other a, P-unsaturated compounds to give y, 5-unsaturated compounds. Vinyllithium reagents can also be converted to secondary alcohols with trialkylb o r ane s. 

A83543A aglycon 595 f. acetic acid 5 acetoxonium ion 538, 762 acetoxymercuration 390 acetylene coupling 268, 275 f. active ester 624 P-acylamino a,p-unsaturated system 111... 

Lewis acid-catalyzed Michael addition of silyl enol ether to a,P-unsaturated system. 

Lewis acid-mediated addition of allylsilanes to carbon nucleophiles. Also known as the Hosomi-Sakurai reaction. The allylsilane will add to the carbonyl compound directly if it is not part of an a,P-unsaturated system (Example 2), giving rise to an alcohol. 

The conjugate addition of enolate anions onto a,P-unsaturated systems is an important synthetic reaction, and is termed the Michael reaction, though this terminology may often be used in the broader... 

Michael-type addition of stabilized carbon donors to electron-withdrawing a,p-unsaturated systems is an efficient method for C-C bond construction. The nitro-group... 

The enol ether is cleaved under acidic conditions in the first step to give ketone 32. In order to suppress isomerization of the ketone to an u,P-unsaturated system, hydrolysis is conducted in the presence of 2-mercaptoethanol, which leads to formation of the S,0 acetal 31. 

The Michael addition of a nitrogen nucleophile to an a,P-unsaturated system has been advocated as a method to prepare P-amino acid derivatives (Scheme 2.24).88 91 However, the method is not... 

The procedure given here stems from our synthetic effort toward (+)-jasplakinolide9 11 that contains the p-amino acid (R)-p-tyrosine.12 This protocol permits the introduction of the desired carbon substituted at the p-site in an enantioselective manner. This approach contrasts with previous methodologies, which develop the chiral center via conjugate addition of an amine to an a,p-unsaturated system,13 reduction of a C=C or C=N functionality,14 or C-C bond formation involving imines and enolate derivatives.15... 

Mechanistically, the one-pot transformation can be rationalized by a sequence of chemoselective coupling of ort/to-halogenated (hetero)aromatic acid chlorides 81 and electron rich terminal alkynes 4, followed by nucleophilic addition of the sulfide ion to the a,p-unsaturated system 86 to furnish the anionic Michael adduct 87, and finally an intramolecular nucleophilic aromatic substitution in the sense of an addition-elimination process concludes the sequence (Scheme 46). 

Another frequent use of (1) and its enantiomer is the stereospecific conjugate addition of carbonyl compounds to a,p-unsaturated systems. Most published examples contain chiral imine derivatives of cyclic ketones, which add to a,p-unsaturated esters and ketones in a highly stereoselective manner (eq 13 and eq 14). When the ketone is not symmetrically substituted, reaction usually occurs at the most substituted a-position, including those cases where the ketone is a-substituted by oxygen (eq 15). High stereoselectivity can also be achieved when the Michael acceptor is other than an unsaturated ketone or ester, such as a vinyl sulfone (eq 16). Intramolecular variations of this transformation have also been described (eq 17). ... 

Enantioselective Copjugate Additions. The use of chiral imines for the enantioselective conjugate addition of carbonyl compounds to a,p-unsaturated systems is well established, mostly with imines derived from a-methylbenzylamine. Recently, (1) has been used to effect the Michael addition of a 4-piperidone to acrylonitrile and methyl acrylate (eq 2) ... 

The cycloadditions of (Ti -allyl)Fp complexes to alkenes proceed with high chemoselectivity. Only highly activated alkenes such as methylenemalonates, benzylidenemalononitrile, TCNE or I,2-di-cyano-4,5-dichloroquinone will participate in the reaction. With the less electrophilic a,p-unsaturated systems, cycloaddition can only be effected with Lewis acid activation. Thus the cycloadduct (6) is formed in reasonable yield (as a mixture of stereoisomers) from (3) and cyclohexenone using freshly sublimed AlBn (equation 4). The same reaction gives only a 8% yield with Aids. The exclusive formation of a ci.r-hydrindanone system can be explained by suprafacial attack of the enone on the allyl unit, which is then followed by another suprafacial ring closure of the dipolar intermediate, affording the thermodynamically preferi cyclic system (7a) and (7b). ... 

Generalizing about regioselectivity in a.p-unsaturated systems is much less straightforward. There can be as many as three acidic sites that could undergo deprotonation and predicting a priori which might be preferred is difficult. There are instances of deprotonation at the least highly substituted of several posi-... 

The Wilkinson catalyst selectively hydrogenates the sterically less-hindered double bond. The trisubstituted double bond, which is also part of an a,p-unsaturated system, is stable under these relatively mild hydrogenation conditions. 

In the LUMO, the largest coefficient is on the P carbon of the a,p-unsaturated system, shown with an asterisk. And it is here, therefore, that nucleophiles attack. In the reaction you have just seen, the HOMO is the methoxide oxygen s lone pair, so this will be the key orbital interaction... 

Lewis acids prefer to lie syn to the smaller substituent of the carbonyl, e.g. sy/t to H for aldehydes, anti to —OR for simple alkyl esters. In a,p-unsaturated systems, Lewis acid coordination syn to the double bond favors the s-trans conformation, but in two crys structures, where coordination anti to the alkene occurs, s-cis complexes are observed. " Finally, chelation with titanium and tin occurs readily and yields stable, crystalline complexes. 

P-Hydroxy esters may be alkylated via their dilithium dianions. Deprotonation of the hydroxy group by the base prevents its elimination to form an a,P-unsaturated system. Two recent publications by Prater et alP and by Seebach et al ° provide summaries of the results of the alkylations of nonracemic... 

As for the reaction between dialkyl phosphites and a,P-unsaturated systems, a-cyano- - and a-carboxy acrylonitriles react with triethyl phosphite in alcohol to give the conjugate addition products in good yields (85-90%). 

Addition of hydrazines to 1,3-difunctional compounds is one of the most common methods employed for the preparation of pyrazoles. For example, several synthesis of pyrazoles have been reported where azide reagents are added to a,P-unsaturated systems. Reactions of trifluoroacetyl enol ether (thiophene) 1 with hydrazines afforded 3-(2-furyl) or 3-(2-thienyl)pyrazoles 2 <05S2744>. A regiospecific one-pot synthesis of trifluoromethyl-substituted heteroaryl pyrazolyl ketones has also been disclosed <05JHC631, 05JHC1055>. 1,3,5-... 

Michael addition of aromatic or heterocyclic aldehydes (via cyanohydrins) to a,p-unsaturated systems. Also addition of an aliphatic aldehydes catalyzed by thiazolium ylids (see 1st edition). 

The cyclic C-17 a-P-unsaturated butenolide (lactone) could be replaced with a small group of what can be considered noncyclic bioisosteres. The requirements seem to be at least an a-P-unsaturated system that also permits a partial positive charge on the P-carbon, as long as the system is not extended (as in D) or bulky (as in C, when R = C2H5). 

The diastereoselective ultrasonically induced zinc-copper 1,4-addition of alkyl iodides to chiral a, P-unsaturated systems in aqueous media was studied by Suares and co-workers the Z-isomer gives good diastereos-electivities while reactions with the E-isomer are nonstereoselective. The 1,4-addition to chiral y, a-dioxolanyl-a, P-unsaturated esters also proceeds with good yields (51-99%) (Eq. 10.29). " ... 

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