Ene reactions carbonyl

The class of ene reactions with carbonyl compounds as the enophile, which we denote the carbonyl-ene reaction [45], is an efficient alternative to the carbonyl addition reaction of allylic metals (Sch. 11). 

This limitation has been overcome by the use of vinylic sulfides and selenides instead of mono- and 1,2-disubstituted olefins. With these substrates, the ene products are formed with almost complete enantioselectivity and high diastereoselectivity [53], 

The synthetic utility of the vinylic sulfide and selenide approach is exemplified by the synthesis of enantio-pure (i )-(-)-ipsdienol, an insect aggregation pheromone (Sch. 13) [54], Kabat and Uskokovic have demonstrated the asymmetric catalytic synthesis of la,25-dihydroxyvitamin D3 (la,25(OH)2D3) A-ring synthon by means of a glyoxylate-ene reaction catalyzed by BINOL-Ti complex (1) (Sch. 14) [55]. 

The synthetic potential of the asymmetric catalytic carbonyl-ene reaction depends greatly on the functionality possible in the carbonyl enophile. The types of enophile that can be employed in the asymmetric catalytic ene reaction have, however, previously been limited to aldehydes such as glyoxylate [49,51-53,55,56] and chloral [50,57]. It is, therefore, highly desirable to develop other types of carbonyl enophile to provide enantio-enriched molecules with a wider range of functionality. We have thus developed an asymmetric catalytic fluoral-ene reaction [58], which is 

BINOL-Ti catalysis can also be used for the carbonyl-ene reaction with formaldehyde or vinyl and alkynyl analogs of glyoxylates in an asymmetric catalytic desymme-trization (vide infra) approach to the asymmetric synthesis of isocarbacycline analogs (Sch. 16) [61]. 

The heterogeneity of the catalysis was confirmed by an investigahon of the liquid-phase supernatants over the solid-state catalysts after a catalytic cycle. Neither the ligand nor catalyst achvity in the Michael reaction were observed in the supernatant solution for the catalyst 3d. The heterogenized ALB catalyst 3d was recovered by syringe removal of the supernatant and rinsing with fresh solvent 

3a linker = 1,2-phenylene 3b linker = 1,3-phenylene 3c linker = 1,4-phenylene 3d linker = single bond 

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Johnson J. S., Evans D. A. Chiral Bis(Oxazoline) Copper(II) Complexes Versatile Catalysts for Enantioselective Cycloaddition, Aldol, Michael, and Carbonyl Ene Reactions Acc. Chem. Res. 2000 33 325-335... 

Mikami K. Asymmetric Catalysis of Carbonyl-Ene Reactions and Related Carbon-Carbon Bond Forming Reactions Pure Appl. Chem. 1996 68 639 644 Keywords hefero-Diels-Alder reactions, asymmetric catalysis... 

The carbonyl-ene reaction is also very useful, and often gives synthetically... 

Another successful reaction of aldehyde 56 is the diastereoselective carbonyl-ene reaction, pictured in Scheme 44, leading to products 60 [63]. 

Scheme 10.16 Carbonyl-ene reactions of pyruvates with 1,1-disubstituted olefins with aminosulfoximine ligand.

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

The best carbonyl components for these reactions are highly electrophilic compounds such as glyocylate, pyruvate, and oxomalonate esters, as well as chlorinated and fluorinated aldehydes. Most synthetic applications of the carbonyl-ene reaction utilize Lewis acids. Although such reactions may be stepwise in character, the stereochemical outcome is often consistent with a cyclic TS. It was found, for example, that steric effects of trimethylsilyl groups provide a strong stereochemical influence.28... 

Visual models, additional information and exercises on the Carbonyl-Ene Reaction can be found in the Digital Resource available at Springer.com/carey-sundberg. 

The use of Lewis acid catalysts greatly expands the synthetic utility of the carbonyl-ene reaction. Aromatic aldehydes and acrolein undergo the ene reaction with activated alkenes such as enol ethers in the presence of Yb(fod)3.35 Sc(03SCF3)3 has also been used to catalyze carbonyl-ene reactions.36... 

The function of the molecular sieves in this case is believed to be as a base that sequesters the protons, which otherwise would promote a variety of side reactions. With chiral catalysts, the carbonyl ene reaction becomes enantioselective. Among the successful catalysts are diisopropoxyTi(IV)BINOL and copper-BOX complexes. 

Most carbonyl-ene reactions used in synthesis are intramolecular and can be carried out under either thermal or catalyzed conditions,43 but generally Lewis acids are used. Stannic chloride catalyzes cyclization of the unsaturated aldehyde 5. 

Fig. 10.2. Structures of complexed aldehyde reagent (a) and transition structure (b) for enantios-elective catalysis of the carbonyl-ene reaction by BINOL-Ti(IV). Reproduced from Tetrahedron Lett., 38, 6513 (1997), by permission of Elsevier.

Carbonyl-ene reactions can be carried out in combination with other kinds of reactions. Mixed acetate acetals of y,8-enols, which can be prepared from the corresponding acetate esters, undergo cyclization with nucleophilic capture. When SnBr4 is used for cyclization, the 4-substituent is bromine, whereas BF3 in acetic acid gives... 

Section 10.1.2.2 describes another tandem reaction sequence involving a carbonyl-ene reaction. 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

Pinacol Rearrangement in Tandem with the Carbonyl-Ene Reaction. Overman and co-workers have developed protocols in which pinacol rearrangement... 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Scheme 1.16. Indium(lll)-catalyzed domino carbonyl-ene reaction...

A simple synthesis of fluorenes as 4-297 was developed by Schafer and coworkers, also using a combination of a Claisen rearrangement and a carbonyl ene reaction (Scheme 4.63) [100]. Heating 4-295 in xylene at 180 °C led to 4-297 as a single diastereomer in 73 % yield the phenol 4-296 can be assumed as an intermediate, but this could not be detected in the reaction mixture. 

Tietze and coworkers [117] also used a metallo-ene reaction as the initiating step for the synthesis of the BCD-ring portion of steroids, which is then followed by a carbonyl-ene reaction. 

A full account5 describes the enantioselective carbonyl-ene reaction of... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

The alkene 1-decene (24) was poorly reactive in the carbonyl-ene reaction with ethyl mesoxalate and required a temperature up to 170 °C for a very long time (5 h) [42]. When performed in a homogeneous liquid medium at the same temperature but under the action of MW irradiation the reaction gave a similar result. Reaction time was appreciably shortened by use of GS/MW coupling [30]. Thus, irradiation at 60 W for only 10 min led to the ene adduct 25 in 50% yield (Scheme 7.2). Under these conditions a maximum temperature of 230 °C was measured. To obtain the same yield with conventional heating at 170 °C reaction for 1 h is required. The stereoselectivity of the reaction was not related to the mode of heating. A higher con-... 

This methodology has been extended by the same author to include carbonyl-ene reactions [37]. The cyclization of (+)-citronellal (19) to pulegols 20 and 21 is faster... 

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