Preparation and Structure of Dienophiles

A multitude of Msulfinyl compounds and sulfur diimides bearing a variety of substituents on the nitrogen atom(s) have been prepared. The Al-sulflnyl compounds are commonly generated by treatment of the parent aniline, amine, sulfonanude, etc., with thionyl chloride and pyridine [Eq. (3)]. 

The resulting Al-sulfinyl derivatives can often be distilled and/or crystallized but are water sensitive and thus are frequently prepared in situ for subsequent cycloaddition reactions. Symmetrically substituted sulfur diimides can usually be prepared by the reaction of SCI2 or S2CI2 with the parent NH2 compound in the presence of a base such as pyridine or triethylamine [Eq. (4)].  

N-DichIorosulfoiiainides or A. N-dichlorocarbamates, when treated with elemental sulfur, also afford diimides [Eq. (5)]. 

Unsymmetrical sulfur diimides are commonly [N epared by two methods. Treatment of a N,lV -l is(arylsulfonyl)sulfur diimide with an equivalent of an amine leads to the displacement of one sulfonyl group [Eq. (6)].  

Alternatively, an amine and an N-substituted dichlorosullimide will react to yield an unsymmetrical sulfur diimide [Eq. (7)].  

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Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

The structure of A -sulfinyl compound 39 was solved using a single crystal grown by the slow evaporation of a solution of dichloromethane (DCM) and hexane (Figure 7) <2003T4651>. The A -sulfinyl compound crystallizes with two molecules in a unit cell. This work provides additional evidence for the (Z)-preference of this dienophile used in [4-1-2] cycloaddition reactions to prepare 1,2-thiazines. 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

Vinyl nitroso compounds have proven to be rather interesting species since they can act as either lit or 4ir components in Diels-Alder cycloadditions. The particular reaction which occurs is dependent upon the structure of the vinyl nitroso compound and the diene which are used. For example, vinyl nitroso compound (112), prepared from oxime (111), reacts as a dienophile (equation 44). On the other hand, nitroso compound (113) (equation 45) reacts with cyclopentadiene to give oxazine (114). Not enough data are presently available to interpret these results satisfactorily. 

The optically pure, structurally characterized zirconocenium tert- butoxide complex l(S,S)-(EBIH)Zr(OBut)(THF)]BPh4 (967, Scheme 242) was prepared by treatment of the corresponding dimethyl complex (A,A)-(EBIH)ZrMe2 966 with /< 7/-butanol in toluene followed by in situ protonolysis with [HNEt3]BPh4 in THF. The complex catalyzes the asymmetric Diels-Alder reaction between cyclopentadiene and various dienophiles.732 The enantiopure zirconocene bis(triflate) complex (A, ST)-(EBIH)Zr(OTf)2 968 also efficiently catalyzes the asymmetric Diels-Alder reaction between cyclopentadiene and oxazolidinones.733,734... 

Small helical molecules are of interest because of their photophysical and chiroptical properties. Helicenophanes, i.e. helical molecules containing the [2.2]paracyclophane moiety, have been studied due to the peculiar structural properties of the cyclophane framework. Enantiopure compounds have extraordinarily high specific rotation values. Some helical cyclophanes have been prepared " by cycloadditions between [2.2]paracyclophane-based dienes 19 and 20 with dienophiles 1 and 21 (Scheme 7.6). 

Draw the structure of the cycloadduct 5 and explain why the preparation of this compound is best carried out as a one-pot procedure, rather than by isolation of the diene and separate heating with the dienophile in toluene. 

N-Phenylmaleimide, the product prepared in Experiment [24B], can act as a dienophile in the Diels-Alder reaction (see Experiments [14] and [15]). Draw the structure of the product that would be formed by the treatment of N-phenylmaleimide with (a) 3-sulfolene under the conditions given in Experiment [14] and (b) furan. 

Since the six carbons shown above have 10 additional bonds, the variety of substituents they carry or the structures they can be a part of is quite varied, making the Diels-Alder reaction a powerful synthetic tool in organic chemistry. A moment s reflection will convince us that a molecule like structure [XVI] is monofunctional from the point of view of the Diels-Alder condensation. If the Diels-Alder reaction is to be used for the preparation of polymers, the reactants must be bis-dienes and bis-dienophiles. If the diene, the dienophile, or both are part of a ring system to begin with, a polycyclic product results. One of the first high molecular weight polymers prepared by this synthetic route was the product resulting from the reaction of 2-vinyl butadiene [XIX] and benzoquinone [XX] ... 

The cationic aqua complexes prepared from traws-chelating tridentate ligand, R,R-DBFOX/Ph, and various transition metal(II) perchlorates induce absolute enantio-selectivity in the Diels-Alder reactions of cyclopentadiene with 3-alkenoyl-2-oxazoli-dinone dienophiles. Unlike other bisoxazoline type complex catalysts [38, 43-54], the J ,J -DBFOX/Ph complex of Ni(C104)2-6H20, which has an octahedral structure with three aqua ligands, is isolable and can be stored in air for months without loss of catalytic activity. Iron(II), cobalt(II), copper(II), and zinc(II) complexes are similarly active. 

Constrained -amino acids, which have gained widespread use in peptide design and are important for controlling secondary structures, were prepared by Kotha and colleagues76 via Diels-Alder reactions of outerring diene 56 with several dienophiles, followed by... 

In early studies of these reactions, the turnover efficiency was not always high, and stoichiometric amounts of the promoters were often necessary to obtain reasonable chemical yields (Scheme 105) (256). This problem was first solved by using chiral alkoxy Ti(IV) complexes and molecular sieves 4A for reaction between the structurally elaborated a,/3-unsaturated acid derivatives and 1,3-dienes (257). Use of alkylated benzenes as solvents might be helpiul. The A1 complex formed from tri-methylaluminum and a C2 chiral 1,2-bis-sulfonamide has proven to be an extremely efficient catalyst for this type of reaction (258). This cycloaddition is useful for preparing optically active prostaglandin intermediates. Cationic bis(oxazoline)-Fe(III) catalysts that form octahedral chelate complexes with dienophiles promote enantioselective reaction with cyclopentadiene (259). The Mg complexes are equally effective. 

The reaction of vinylindoles with dienophiles has been used for the preparation of natural products and synthetic compounds with pharmacological interest because their substituted carbazole structures were more easily accessible by these cycloadditions than by other routes. 

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