Aldehydes and Dienes

With 1.5 equiv of aldehyde and diene relative to amine. With 10 mol% Triton X-100 added. 

Catalytic Asymmetric Diels-Alder Reaction. Amino alcohol (1) combined with Boron Tribromide generates a chiral catalyst for the asymmetric Diels-Alder reaction (97% ee) of unsaturated aldehydes and dienes. ... 

Chiral tridentate chromium(III) complexes catalyze highly enantio- and diastereo-selective hetero-Diels-Alder reaction between various aldehydes and dienes with one oxygen substituent (Sch. 60) [206]. Complex formation between catalysts and aldehydes could not be detected by IR and the successful use of acetone as a solvent casts doubt on a simple Lewis acid mechanism. 

Klin dig s cationic iron(II) complex 39a, derived from tra s-l,2-cyclopentanedi-ol, is a stable, isolable brown solid that possesses sufficient Lewis acidity to catalyze Diels-Alder reactions between unsaturated aldehydes and dienes [95]. The highest selectivities and yields were realized using bromoacrolein as the dienophile (Scheme 32). Further inspection reveals that dienes less reactive than cy-clopentadiene give cycloadducts in higher yield and enantioselectivity, a characteristic that is even more impressive when one considers that the endo and exo transition states produce enantiomeric products for isoprene and 2,3-dimethyl-butadiene. Cyclohexadiene may be used in the reaction with bromoacrolein to afford the cycloadduct in 80% de and >99% ee. In the case of cyclopentadiene. 

Initial investigations focused on the use of thermal and high-pressure conditions to perform reactions between aldehydes and dienes.Under these conditions the only products observed are those which... 

Nonpolar solvents e.g. benzene) have also led to aldol products." Topology and stereochemistry can be a function of aldehyde and diene used in the reaction (vide infra). 

Yamamoto and cowoikers have recently found a chiral aluminum catalyst (79) that catalyzes the hetero cyclocondensation reaction (Scheme 28). In the reaction of benzaldehyde with diene (14) an enantiofacial selectivity of up to 95% ee was observed. A summary of substituted aldehydes and dienes used in this study is given in Table 20. As with the Eu(hfc)3 catalyst, the more substituted dienes give higher enantiofacial selectivity. Aromatic aldehydes are the best substrates and xylyl groups give the most efficient catalysts. The aluminum catalyst has also been extended to other simple aldehydes (Table 21) and has recently been used for the resolution of racemic dienophiles. ... 

In summary, the condensation of activated dienes with aldehydes is a versatile tool in organic synthesis. The reaction is applicable to both complex and simple aldehydes and dienes a list of the dienes which were used in cyclocondensation reactions is given in Figure 5. The high degree of stereoselectivity also makes the cyclocondensation of activated dienes with aldehydes a useful synthetic tool. 

This reaction type has been applied to several other aldehydes and dienes and can be used in the synthesis of optically pure natural and non-natural carbohydrate-type systems, such as L-glucose. Hetero-Diels-Alder cycloadditions of this type can also be catalyzed by other chirally modified transition metal complexes, such as CpRu(CH2 = CH2)L3PF6 [L2 = (S)-Chi-raphos, (-)-Diop]68, (binaphthol)TiX269 70 102, vanadium103 104, or carbohydrate-modified titanium catalysts105. 

The catalyzed cycloaddition of alkoxy or amino aldehydes has been the subject of extensive studies. The influence of different Lewis acids and protective groups on the diastereoselectivity has been investigated for various types of aldehydes and dienes. Induced and simple diastereoselectivities (endoiexo) in the [4 + 2] cycloaddition of aldehydes 1 are highly dependent on the Lewis acid applied as catalyst. Several reactions ofa-alkoxyaldehydes 1 to dienes 2 under Lewis acid catalysis have been performed to give adducts 3 and 435. Among the catalysts tested (see table below) the best results were achieved for the magnesium bromide catalyzed cycloaddition of 1 to several dienes. Adduct 3 was obtained as a single compound. 

Some exceptions to the general rules occur. Cyclopentene is completely combusted, undoubtedly because of the high reactivity of cyclo-pentadiene. 4,4-Dimethyl-1-pentene is expected to produce an unsaturated aldehyde, but instead 2,3-dimethylpentadiene is the initial product. A methyl shift from a quarternary carbon is apparently easy, permitting formation of a diene instead of the oxygenated compound. 3,3-Dimethyl-l-butene is not expected to react at all under the general rules, but here also a methyl shift occurs so that diene, olefin aldehyde, diene aldehyde, and diene dialdehyde are formed. The reactivity of the latter olefin relative to 1-butene, measured by oxidation of a mixture at low conversion, was 0.21, while that of 4,4-dimethyl-1-pentene was 0.75. These reactivities suggest that isomerization occurs before reaction for 3,3-dimethyl-l-butene, while isomerization probably occurs after the aUyl intermediate is formed in the case of the pentene. 

Allylic olefins of higher molecular weight than propylene can also be converted to the corresponding a-3 unsaturated nitriles, aldehydes, and dienes by catalytic vapor phase oxidation and ammoxidatlon. Examples include the conversion of isobuthylene to methacrylonitrile ( eq. 14) or methacrolein ( eq. 16 ), a-methyl styrene to atroponitrile ( eq. 15 ) or atropoldehyde ( eq. 17), and 2-methylbutene to isoprene (eq. 18). 

In 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,p-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malim-ide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan s conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation). Scheme 3.2 [7]. 

Since we are dealing with boron reagents, oxygen should be a particularly efficient control element and this was nicely demonstrated in the Ni-mediated borylative Mori-Tamaru-couphng of aldehydes and dienes. 

Tf2NH or B(C6F5)3. While B(C6F5)3 provided Diels-Alder products of a,P-unsaturated aldehydes and dienes selectively, Tf2NH gave a Diels-Alder product of a,P-unsatureted ketones and dienes preferentially. They proposed that this reversal of chemoselectivities arises from a combination of steric as well as electronic effects of the dienophiles (Table 2.20, Figure 2.7). 

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