Diene cyclocondensation

Danishefsky, S. J. Simoneau, B. Total synthesis of ML-236A and compactin by combining the lactonic (silyl) enolate rearrangement and aldehyde-diene cyclocondensation technologies./. Am. Chem. Soc. 1989, 111, 2599-2604. 

Cyclocondensation reactions with perfluoroalkyl-subsbtuted CO and CN multiple bond systems can be divided into several subgroups, according to the charge pattern of both reactants On the basis of this simple concept, hetero-l,3-dienes should undergo two types of condensation reactions, classified by the number of skeleton atoms of the diene being incorporated into the ring system (equation 10). 

The chiral BIN0L/Ti(0-i-Pr)4 combination has also been used as a very enantio-selective catalyst for the cyclocondensation of polyfluoroalkylaldehydes with Danishefsky s diene leading to polyfluoroalkyldihydropyrenones in moderate yields (35-60%) and with high ee (90-98.5% ee) [20]. 

Ghosh et al. (228) investigated the cycloaddition of Danishefsky s diene (1-methoxy-3-trimethylsiloxybutadiene, 334) and glyoxylate esters. The reaction provides a mixture of the Mukaiyama aldol product (336) and dihydropyrone (335). Treatment of the unpurified reaction mixture with trifluoroacetic acid induced the cyclocondensation to provide dihydropyrone (335) in 70% combined yield and 72% ee, Eq. 188. 

For highly functionalised dienes and their equivalents, also very useful for designing organic syntheses involving cycloaddition and cyclocondensation reactions, see S. Danishefsky, CHEMTRACTS Organic Chemistry, 1989, 2, 273-297. 

The cyclocondensation of Danishefsky s diene 35 with alaninals of type 25, contrary to diene 32, requires neither elevated pressure nor high temperature. The zinc bromide-mediated reaction of 35 with alaninal 25 was followed by acidic workup, resulting in removal of both the trimethylsilyl protection and the ethoxy group [45,46] (Scheme 13). 

Cyclocondensation of 2-siloxy dienes and aldehydes is catalyzed by 1 mol % of a soluble lanthanide complex, Eu(hfc)3, and gives the hetero-Diels-Alder adduct in up to 58% ee (Scheme 107) (263). Upon treat-... 

Quinolines have also been prepared on insoluble supports by cyclocondensation reactions and by intramolecular aromatic nucleophilic substitution (Table 15.26). Entry 10 in Table 15.26 is an example of a remarkable palladium-mediated cycloaddition of support-bound 2-iodoanilines to 1,4-dienes. Reduction of the nitro group of polystyrene-bound 2-nitro-l-(3-oxoalkyl)benzenes with SnCl2 (Entry 11, Table 15.26) leads to the formation of quinoline /Y-oxides. These intermediates can be reduced to the quinolines on solid phase by treatment with TiCl3. 4-Quinolones have been prepared by thermolysis of resin-bound 2-(arylamino)methylenemalonic esters [311]. 

Cyclocondensations with aldehydes.2 The diene 1 reacts with aldehydes to give products of type 2 and/or 3, depending on the Lewis acid catalyst. With BF3 etherate, the rron.v-adduct 3 predominates, whereas with ZnCl2 catalysis the civ-adduct 2 is... 

Cyclocondensation of dioxygenated 1,3-dienes with aldehydes. In the presence of ZnCl2 in benzene or BP3 etherate in ether, this diene 1 undergoes cyclization with a wide variety of aldehydes to afford 2,3-dihydro-y-pyrones (equation I). The products... 

Cyclocondensation with imines. The diene (1) undergoes a similar [2 + 4] cycloaddition with imines, even nonactivated imines. Use of a three- or fourfold excess of the diene improves the yield of 5,6-dihydro-y-pyridones (equation l).4... 

The cyclocondensation of the diene (1) with (R)-glyceraldehyde acetonide (9) results in high asymmetric induction at C5 of the dihydropyrone (10). The configuration (S) was established by degradation to 2-deoxyribonolactone (11). The result is in accord with the Cram rule for addition to chiral carbonyl compounds. The paper also describes conversion of the pyrone (10) to chiral 2,4-dideoxy-D-glucose. 

The synthetic value of this reaction has been enhanced by the development of a wide range of methodologies for glycal synthesis from 0-acylatcd glycosyl halides1 or from noncarbohydrate precursors. By use of the Lewis acid-catalyzed diene-aldehyde cyclocondensation reaction, glycals of natural and non-natural sugars can be obtained (Scheme 4).31... 

Scheme 4. Synthesis of glycals by Lewis acid-catalyzed diene-aldehyde cyclocondensation reaction (P-R2 gluco series a-R2 galacto series).

Methods based on the cyclization of diene derivatives have been described. Thus, chalcose (152) has been synthesized by a cyclocondensation reaction of the silyloxy diene 166 with acetaldehyde (Scheme 50).241... 

S. J. Danishefsky, J. F. Kerwin, and S. Kobayashi, Lewis acid catalyzed cyclocondensation of functionalized dienes with aldehydes, J. Am. Chem. Soc., 104 (1982) 358-360. 

The Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) reaction is a fast procedure to obtain dihydropyrones such as 28.4... 

LACDAC Lewis acid catalyzed diene-aldehyde cyclocondensation... 

The synthesis of the C9-C15 subunit 64 commenced with the cyclocondensation of aldehyde 67 and diene 68 to provide dihydropyrone 66 (Scheme 16) [118]. A Luche reduction [119, 120] and acid-mediated Ferrier rearrangement gave lactol 69 [121], installing the 03-04 (Z)-trisubstituted olefin. A further five steps... 

S. Danishefsky, Cycloaddition and Cyclocondensation Reactions of Highly Functionalized Dienes Applications to Organic Synthesis, Chemtracts Org. Chem. 1989, 2, 273—297. 

A particularly elegant example is the application of Danishefsky s diene [107] to the total synthesis of carbohydrates and carbohydrate derivatives. While it was known that activated aldehydes undergo cycloaddition with electron-rich dienes, the process was not efficient with typical aldehydes under thermal conditions. A major breakthrough was realized [108] with the development of the Lewis acid-catalyzed diene-aldehyde cyclocondensation (LACDAC) reaction, which provided a new strategy for the synthesis of carbohydrates and other polyoxygenated natural products (Scheme 1.4) [109],... 

Larsen SD, Grieco PA (1985) Aza Diels-Alder reactions in aqueous solution cyclocondensation of dienes with simple iminium salts generated under Mannich conditions. J Am Chem Soc 107 1768-1769... 

Cyclocondensation with carbonyl compounds. This diene undergoes condensation with both aldehydes and ketones in the presence of 1 cquiv. of zinc chloride or BF, etherate to afford unstable orthoester adducts, whii h are hydrolyzed to 8-lactones (equation I). The europium(lll) catalysts Eu(fod), and the chiral Eu(hfc), are also excellent catalysts,... 

Cyclocondensation with aldehydes (II, 332 333). The cyclocondcnsation of aldehydes with trimethylsilyloxydienes to provide 2.3-dihydro-4-pyroncs has been studied in the most detail with this diene. Two pathways base been identified. In reactions catalyzed by ZnCIi, MgBr, and a lanthanide shift reagent uch as Eu(fod), a pericyclic pathway is suggested by isolation of the initial cycloadduci 2 with the expected e/ir/o-seleetivity. In the presence of acid, this adduct is converted into a <7.v-2,3-dihydro-4-pyronc (3). Only traces of the /ra/i.v-isomer (4) arc formed. In coniiast, the BF,-catalyzed reaction results... 

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

---