N-Sulfinyl dienophiles

Numerous studies have dealt with different types of sulfur-containing hetero-dienophiles. Thus, hetero Diels-Alder reactions of N -sulfinyl dienophiles have been thoroughly studied by Weinreb et al. [454] the resulting cycloadducts represent useful and versatile intermediates in the synthesis of homoallylic amines [455] or pyrroles [456]. Further work using this type of S = N dienophiles... 

Asymmetric hetero Diels-Alder reactions of N-sulfinyl dienophiles with chiral dienes have been found to proceed with very good induced diastereoselec-tivities [459]. 

In 2002 the same author demonstrated the usefulness of this method in a rather demanding context including an intramolecular cycloaddition with an W-sulfinyl urea as a new type of N-sulfinyl dienophile (Scheme 60) [144]. As key steps in the total synthesis of freshwater cyanobacterial hepatotoxins, ( , )-diene 238 was transformed into N-sulfinyl urea 239 which immediately cycloadds intramolecularly yielding tricycle 240 as a single isomer in excellent yield. After reaction with phenylmagnesium bromide the intermediate allylic sulfoxide rearranges cleanly to diastereomerically pure allylic alcohol... 

Weinreb, S. M. Synthetic methodology based upon N-sulfinyl dienophile [4 + 2]-cycloaddition reactions. Acc. Chem. Res. 1988, 21,313-318. 

Two groups have recently examined enantioselective N-sulfinyl dienophile Diels-Alder reactions. In one case, Whitesell et al. found that a phenylmenthol derived N-sulfmyl carbamate adds to ( , )-2,4-hexadiene under Lewis acid catalysis to afford a single diasteteomer (equation 52). If the Lewis acid was omitted, a complex mixture of cycloaddition products was obtained. Attack of the diene on the N-sulBnyl dienophile as shown in the equation would rationalize the observed results. The site of Lewis acid complexation, however, is unknown. 

The Weinreb group has recently examined the reaction of chiral N-sulfinyl dienophile 23, prepared from (+)-camphor, with 1,3-cyclohex-adiene (Scheme 1-VIII). Whereas the uncatalyzed cycloadcUtion afforded a mixture of diastereomeric adducts, the reaction promoted by TiCU gave a single adduct 24 having the 35,6/ configuration. Stereochemistry at sulfur in this compound could not be determined. As in the phenylmenthol series, one can reasonably consider two reacting dienophile conformations 23A and 23B (Scheme 1-VIU). If conformer 23A is attacked by the diene in an endo manner from the most exposed face, the observed adduct 24 will be formed. Similarly, if conformer 23B reacts with cyclohexadiene via an exo transition state, 24 will result. 

As stated in the Introduction, N-sulfinyl compounds bearing electron-withdrawing substituents react as heterodienophiles. Arylsulfinyl derivatives usually require heating for a reaction to occur, whereas other types of N-sulfinyl dienophiles will often cycloadd near room temperature or below. In fact, these cycloadditions are sometimes dangerously exothermic when run in the absence of a solvent, and usually an inert solvent such as benzene, toluene, or cyclohexane is used.2 ... 

A number of representative examples of N-sulfinyl dienophile cycloadditions can be found in Table 1-1. As noted above, some adducts undergo... 

Weinreb, S.M., Synthetic Methodology Based Upon N-Sulfinyl Dienophile 4 -i- 2 -... 

Weinreb SM, Garigipati RS, Gainor JA. Natural product s)mthesis via cydoadditions with N-sulfinyl dienophiles. Heterocycles. 1984 21 309-324. 

Gautun reported enantioselective HDA reactions of 1,3-cyclohexadiene with N-sulfinyl dienophiles promoted by chiral Ti(IV)-based Lewis acids [172]. The yields and enantiomeric excesses obtained are heavily dependent on the method of catalyst preparation. Acceptable reproducibility was obtained with Ti(IV) catalysts prepared from Me2TiCl2 and chiral diols. Testing of various diol ligands gave the endo adduct in the yield of up to 69% and with 76% ee (Scheme 14.76). 

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