Miscellaneous Hetero Diels-Alder Reactions

In addition to the mentioned oxa-, aza- and thia- 1,3-butadienes and the hitherto discussed dienophiles, a multitude of polyhetero dienes and -dienophiles have been employed in recent hetero Diels-Alder reactions. The array of heteroatoms amenable for such cycloadditions is by no means restricted to oxygen, nitrogen and sulfur since there exist numerous reactions involving less common heteroatoms such as phosphorus, silicon or selenium. 

Hetero Diels-Alder reactions of l-thia-3-aza-l,3-butadienes have also attracted theoretical interest resulting in a study dealing with kinetic and thermodynamic parameters of such cycloadditions [444]. 

N-Acylimines which may react as l-oxa-3-aza-l,3-butadienes represent a class of heterodienes which exhibit a close relationship to l-thia-3-aza-l,3-butadienes [13]. A very impressive application of such an l-oxa-3-aza-l,3-butadiene has been worked out by Swindell et al.[445]. The asymmetric hetero Diels-Alder reaction described therein opens a very elegant approach to the A-ring side chain of taxol. This synthesis takes advantage of the bulky chiral auxiliary attached to the dienophile 6-5 which upon cycloaddition with the l-oxa-3-aza-1,3-butadiene 6-4 yielded the 1,3-oxazine derivative 6-6. Subsequent hydrolysis, hydrogenolysis and transesterification gave the methyl ester of the taxol A-ring side chain 6-7 in good endo and excellent zr-facial selectivity (Fig. 6-2). 

less extensively investigated bisheterodienes are 1,4-dioxa-, 1,4-dithia-and l-oxa-4-thia-l,3-butadienes. Thus, several 1,4-benzodioxines have been synthesised by Nair et al. starting from o-benzoquinones [446,447]. In an earlier work, Dondoni has studied their reactivity towards the C=C double bond of several oxazoles [448]. Cyclic dithiaoxalates have been employed as 1,4-dithia- 

Conceptionally related glycosidation methodologies stem from Leblanc s [452] and Schmidt s groups [453]. They involve azodicarboxylates (which actually are well known to react as heterodienophile, see Sect. 3.4.) as l,2-diaza-4-oxa- 

---

Syntheses with Miscellanous Hetero Diels-Alder Reactions... 

Miscellaneous. There are several other reports on the application of this ligand to catalytic asymmetric reactions, although enantioselectivities are modest. Those reports include the Mukaiyama-Michael reaction, allylation of aldehydes, asymmetric Diels-Alder reaction, Mukaiyama-Aldol reaction of ketomalonate, aziridination reaction of a-imino esters, and asymmetric hetero-Diels-Alder reaction. ... 

The emphasis in this work is on the scope and preparative synthetic utility of the hetero Diels-Alder reaction. No attempt has been made to carefully define or delineate the important mechanistic questions, many of which are as yet unanswered, of the various [4 -I- 2] cycloaddition reactions other than to try to provide a rationale for the facility with which the cycloadditions proceed and to provide a basis for the stereo- and regio-chemical observations. We have purposely excluded reactions of singlet oxygen as a dienophile, since extensive surveys are available elsewhere. Many miscellaneous heterodienophiles and heterodienes have not been covered if in our opinion they are not of general synthetic value. A comprehensive treatment of all recorded hetero [4 + 2] cycloadditions is beyond the scope of this monograph. However, we do hope to provide a broad survey of this reaction type as it exists today in order to furnish a foundation for continued development. 

---