A,p-Enals

E,Z)-l -Dienes.1 This unit, often present in insect pheromones, can be obtained with high stereoselectivity by reaction of an aldehyde with 1 to provide an (E)-a,p-enal (2), which on reaction with a phosphorane generated with BuLi and HMPT provides (E,Z)-dienes almost exclusively. 

The paper reports application of this sequence to a l-alkyl-2-silyloxycyclopro-pane (equation I) to furnish an a,p-enal. 

The above process proceeds with low enantioselectivity when applied to acyclic enones. However the acetals of a,p-enals formed from L-diethyl or L-diisopropyl tartrate react enantioselectively with CHzVZ QHs (2, 134).4 Example ... 

The catalyzed reaction of 1 with a,P-enals takes an unexpected course. The adduct with methacrolein, for example, obtained after silyl ether cleavage does not contain the expected aldehyde group, but has the bicyclic structure 5. Apparently the initial product a undergoes an intramolecular aldol condensation to give b. which undergoes silyl transfertoc, which is hydrolyzed by acid to the 7-hydroxy-bicyclo[2.2.1 Jheptanone 5. 

Oxidation of a,p-enals. Sodium chlorite is superior to other reagents for oxidation of oc,/l-unsaturated aldehydes to the corresponding carboxylic acid, particularly of aldehydes containing an ct-methylene group. In addition, the oxidation is stereospecific. 2-Methyl-2-butene2 was used as the chlorine scavenger. 

DITHIOESTERS 2,4-Bis(methylthio)-2,4-dithiooxocyclodiphosphathiane. a.p-ENALS Bipyridinium chlorochromate. 

Isomerization of 2-ynols.4 This Ru complex in combination with a trialkyl-phosphine is an effective catalyst for isomerization of 2-ynols to a,p-enals in refluxing toluene. 

Asymmetric Diels-AUer reactions The observation that simple acyloxy-boranes such as H2BOCOCH=CH2, prepared by reaction of BH3 with acrylic acid, can serve as Lewis acid catalysts for reactions of the a,P-unsaturated acids with cyclopentadiene (15, 2) has been extended to the preparation of chiral acyloxy-boranes derived from tartaric acid. The complex formulated as 3, prepared by reaction of BH3 with the monoacylated tartaric acid 2, catalyzes asymmetric Diels-Alder reactions of a,P-enals with cyclopentadiene with high enantioselectivity. The process is applicable to various dienes and aldehydes with enantioselectivities generally of 80-97 % ee. 

Selective reductions.1 Zinc bo and a,P-enals at -15° without effc Reduction of azomethines.s Z ary amines or the amine-BH3 compfc alkylation-reduction of nitriles to j... 

Selective reductions.2 Zinc borohydride in DME can reduce saturated ketones and a,p-enals at —15° without effect on a,P-enones or saturated aldehydes. 

Asymmetric allylboration of RCHO. (S)-l reacts with aliphatic or aryl aldehydes or with a,p-enals to form homoallylic alcohols in 92-97% ee and 80-92% chemical yield. The chemical and optical yields are higher than those obtained with B-allyldiisopinocamphenylborane (14,12), with allylboronates modified with tartrates, or with B-allyltrimethylsilylboronates. The high asymmetric induction is believed to result from steric effects rather than electronic effects. 

Prolines.1 The complex 2 undergoes base-catalyzed (CH,ONa) Michael addition to a,p-enals and -enones. Reaction of 2 with acrolein furnishes a dihydro-pyrrole-2-carboxylic acid which is reduced to (S)-proline. 

Dienals. The cyclohexylimine (2) of 1 reacts with carbonyl compounds in THF to give (E,E)-dienals in 65-80% yield. The reaction of 2 with a,p-enals to provide trienals proceeds in generally lower yield (25-45%). 

E)-OL-Methyl-a., -enals.1 The anion of the t-butyl- or cyclohexylimine of a-trialkylsilylpropionaldehyde (1) is known (13, 323) to react with aldehydes to provide a-methyl-a,p-enals as a mixture of (E)- and (Z)-isomers in the ratio 1.3-11 1. However, the crude imine intermediates fsomerize mainly to the (E)-isomers when treated at room temperature with trifluoroacetic acid. 

The chiral acetals of a,p-enals derived from (H,R)-( -I-)-N,N,N, N -tetramethyltartaric acid diamide (9, 47-48) undergo either 1,4- or I. . .-addition of R,AI with high asymmetric induction. The course of reaction can be controlled by the choice of solvent. 1,4-Addition is favored in 1,2-dichloroethane (or toluene) 1,2 addition is the main or only reaction in chloroform. The adducts can be converted into optically active p-alkyl aldehydes or allylic alcohols (Chart I). ... 

Oxidation of allylsUanes to a, -enals. 2-Substituted allylsilanes are oxidized to a,p-enals by reaction with QH5l=0 (2 equiv.) activated with BF, etherate (1 equiv.) in dioxanc. 

Enones (cf. 11, 391-392). PdlOAc). is the preferred catalyst for dehydrogenation of alkenyl allyl carbonates to give a.p-enals or -enones. Use of a phosphine ligand can catalyze allylation/protonation in addition to p-elimination. 

Allylic pinacols. Reduction of ketones bearing an electron-withdrawing group with TiCli in the presence of a,p-enals results in coupling to allylic pinacols in 45 85% yield. Example ... 

Disubstituted 4-isoxazolines 65 were easily converted to a,p-enals 66 by treatment with Mel in THF at reflux temperature. When the same reaction was performed in polar solvents such MeOH, DMF or MeCN the formation of minor amounts of a,p-unsaturated amides 68 was observed. The amides 68 were obtained as sole products in high yields by heating the preformed isoxazolinium salts 67 in MeOH. The new process is believed to proceed through the heterolytic cleavage of the C3-N bond of 67 assisted by the solvent with formation of an allylic tertiary carbocation intermediate <03JOC3718>. 

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes . The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,p-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo exo= 11 89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while p-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and p-positions, high enantioselectivity is observed thus the a-substituent effect overcomes that of the p-substituent. 

OLy -Enals p-Keto diethylacetals, obtained by reaction of ketones with this reagent, can be converted into one-carbon-homologated a,p-enals by reduction (NaBH4) and acid-catalyzed rearrangement. 

E)-OL fi-Enals. The ylide derived from 1 (K2CO3) reacts with aldehydes in THF/ether to give (E)-a,p-enals in 80-95% yield. 

Conjugate addition to enals In the presence of Ni(acac)2, diarylzinc reagents undergo 1,4-addition to a,p-enals in satisfactory yield however, the same reaction with dialkylzinc reagents gives low yields (15%, one example). 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Brdnsted-acid-assisted chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phenylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5-Z7ri(trifluoromethyl)-benzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,P-enals and various dienes. The interesting aspect is the role of water, THE, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

This asymmetric cycloaddition has also been achieved using the ammonium salt derived from amine (8.228) as catalyst. In this approach the acceptor a,p-enal (8.230) is further activated by conversion to iminium ion in situ and even unactivated alkenes such as (8.229) can be used as the donor. 

An alternate approach, pioneered by Kunz and MacMillan, proceeds by reaction of sulfur ylides with a,(3-unsaturated iminium ions, formed by reaction of a,p-enals with enantiomerically pure amines. In this approach the sulfur ylide (9.87) reacts with a range of (3-aryl- and P-alkyl-substituted enals, including (9.88), in the presence of the dihydroindole (9.89) to give the cyclopropane with ees ranging from 89 to 96%. More recently, it has been shown that replacement of the carboxylate functional group in (9.89) with an isosteric tetrazolic acid gives an improved catalyst that effects cyclopropanation with 99% ees in all cases studied. 

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