A,3*unsaturated methylation

Wittig-type reactions.1 In contrast to the corresponding phosphorane reagent, 1 reacts with ketones as well as aldehydes to form a, 3-unsaturated methyl ketones. Two typical products and the yields are formulated. 

The readily prepared and air-stable complex trans 4, catalyzes Diels-Alder reactions between 1,3-dienes and a,]3-unsaturated methyl ketones or enals. Nitro-methane is the best solvent, and rate accelerations are up to a factor of 10 compared to the uncatalyzed reaction and up to 10 compared to catalysis by trifluoroacetic acid (Scheme 10.20) [34]. 

The elimination is completely chemoselective with l-(l-hydroxyalkyl)-5-iactones and with methyl 3-hydroxy-a-selenoalkylcarboxylates (precursors of ( )-a,3-unsaturated methyl carboxylates Scheme 39, b and Scheme 170), 74 ut not with the other stereoisomer which produces a mixture of (Z)-a,3-un-saturated methyl carboxylates (by formal selenenic elimination) and a-seleno-a,3-unsaturated methyl carboxylates (by formal elimination of water). 

In the laboratory of S.V. Ley, the total synthesis of the 3-lactone cholesterol synthase inhibitor 1233A was achieved by using the oxidative decompiexation of a (jt-allyl)tricarbonyliron lactone as the key step. " The (Z)-alkene present in the target was introduced using the S-G modified HWE olefination of an aldehyde with b/s(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate to give the desired a, 3-unsaturated methyl ester in excellent yield. 

Reaction with trialkylboranes. 3-Butyne-2-one, like acrolein (this volume), does not react spontaneously with trialkylboranes, but in the presence of catalytic amounts of oxygen it reacts readily to give a,/3-unsaturated methyl ketones (2)... 

ANNULATION USING A [13-(TRIMETHYLSILYL)ACRYLOYL]SILANE AND THE LITHIUM ENOLATE OF AN a,(3-UNSATURATED METHYL KETONE (1R. 6S. 7S )-4-(tert-BUTYLDI-METHYLSILOXY)-6-(TRIMETHYLSILYL)-BICYCLO[5.4.01UNDEC-4-EN-2-ONE... 

Juvabione, the compound responsible for this activity, was isolated from the balsam fir, Abies balsamea (L.) Miller, and identified as the methyl ester of todomatuic acid, (+)-4(i )-[ 1 R)-S -dimethyl-3 -oxohexyl]-1-cyclohexene-1-carboxylic acid [87]. This compound is a sesquiterpenoid (Fig. (6)) with a cyclohexene group and an a,(3-unsaturated methyl ester group the chemical data for this compound are summarized in Appendix II, Table 1. The IR spectrum suggests that there is a carbonyl ester group present in conjunction with a double bond (1722 and 1645 cm 1) and also an isolated carbonyl group (1712 cm 1) [87]. Mass spectroscopy confirms... 

To improve understanding of mechanistic aspects of Raney nickel s selectivity and activity, a series of seven variously substituted a, 3-unsaturated methyl esters were hydrogenated either under deuterium (deuteriumated) or under nitrogen over deuterated Raney nickel. For comparison, some of the molecules were deuteriumated over Pd/C, and in some instances the Raney nickel was modified with L-glutamic acid. 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

The allylic geminal diacetate 141 undergoes the monoallylation of malonates to give 142 and the two regioisomers 143 and 144[93,94]. The dimethylacetal 145 or ortho esters of aromatic and a,/3-unsaturated carbonyl compounds react with trimethylsilyl cyanide to give the methyl ether of cyanohydrin[95]. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

The catalytic reduction of 2-methyl-3-phenyl-3-isoxazoline (159) produced /3-hydroxypropiophenone (160) (74CPB70). Ring fission also occurred on base treatment of the 3,5-diaryl-3-isoxazoline (161) to give the a,/3-unsaturated oxime (162) (70CI(L)624). 

The alkylation of dienamines has not been studied extensively. Thus the dienamine (44) is reported (43,44) to alkylate at Cj with methyl iodide to give the iminium salt (45), which on hydrolysis gives the alkylated a,)3-unsatur-ated ketone (46). Similar dienamines prepared from A -2-oko steroids. On the other hand, are reported to undergo only N alkylation (45). 

Similarly, methyl vinyl ketone has been added to enamines derived from aldehydes (3,321,324-327) and ketones (3,328), providing a useful extension of the Robinson annelation reaetion. Condensations of enamines with other a, 3-unsaturated ketones can give a variety of diketones (329). 

In the case of t-butyl substituted a,/3-unsaturated ketones, however, no reaction with ketones occurred in the presence of triphenylmethyl fluoroborate instead, a 1,2-methyl shift in the unsaturated ketone accompanied by cyclization afforded a crystalline dihydro-furylium salt. ... 

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 ... 

A ketone vvith a substituent group in its /3 position might be prepared by a conjugate addition of that group to an a,/3-unsaturated ketone. In the present instance, the target molecule has a propyl substituent on the /3 carbon and might therefore be prepared from 2-methyl-2-cyclopentenoneby reaction with lithium dipropylcopper. 

This provides a route to a/3-unsaturated aldehydes (25). 2-Methyl-3-phenylprop-2-enal (25)... 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

Titanium tetrachloride induces reaction with dichloromethyl methyl ether to give a, (3-unsaturated aldehydes.127... 

Complexes 17-19 can be written in one valence structure as a, /3-unsaturated carbonyl compounds in which the carbonyl oxygen atom is coordinated to a BF2(OR) Lewis acid. The C=C double bonds of such organic systems are activated toward certain reactions, like Diels-Alder additions, and complexes 17-19 show similar chemistry. Complexes 17 and 18 undergo Diels-Alder additions with isoprene, 2,3-dimethyl-1,3-butadiene, tram-2-methyl-l,3-pentadiene, and cyclopentadiene to give Diels-Alder products 20-23 as shown in Scheme 1 for complex 17 (32). Compounds 20-23 are prepared in crude product yields of 75-98% and are isolated as analytically pure solids in yields of 16-66%. The X-ray structure of the isoprene product 20 has been determined and the ORTEP diagram (shown in Fig. 3) reveals the regiochemistry of the Diels-Alder addition. The C-14=C-15 double bond distance is 1.327(4) A, and the... 

The introduction of various metal-catalyzed reactions, however, remarkably expanded the scope of the epoxidation of Q,.3-unsaturatcd ketones. Enders et al. have reported that a combination of diethylzinc and A-methyl-pseudoephedrine epoxidizes various o,. j-unsaturatcd ketones, under an oxygen atmosphere, with good to high enantioselectivity (Scheme 23).126 In this reaction, diethylzinc first reacts with the chiral alcohol, and the resulting ethylzinc alkoxide is converted by oxygen to an ethylperoxo-zinc species that epoxidizes the a,/3-unsaturated ketones enantioselectively. Although a stoichiometric chiral auxiliary is needed for this reaction, it can be recovered in almost quantitative yield. 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

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