The hetero Diels-Alder reaction is one of the most important methods for the synthesis of heterocycles. In this article an overview is given for the period since 1989 describing the reaction of heterobutadienes such as oxabutadienes, thiabutadienes, azabutadienes, diaazabutadienes, nitroso-alkenes and nitroalkenes as well as of heterodienophiles such as carbonyls, thiocarbonyls, imines, iminium salts, azo- and nitroso compounds. In addition, several other less common hetero Diels-Alder reactions such as cycloadditions of thiaazabutadienes, oxaazabutadienes, dioxabutadienes, dithiabutadienes, oxathiabutadienes, diazaoxabutadienes as well as the use of N-sulfinyl-phosphaalkynes and other dienophiles are mentioned. A main point of discussion is the stereoselectivity of the reactions and the preparation of enantiopure compounds either using dienes and dienophiles carrying a chiral auxiliary or employing chiral Lewis acids. A point stressed is the synthesis of natural products using hetero Diels-Alder reactions leading to carbohydrates, alkaloids, terpenes, antibiotics, mycotoxins, cytochalasans, antitumor agents and several other classes of natural products.

Hetero diels-alder reactions in organic chemistry

This chapter reviews the transformations used to prepare amidines and N-substituted amidines with particular emphasis on newer methods published since 1993. The first part of the review covers the synthesis of amidines RC(NR1)NR2R3 (where R, R1,R2,R3 are carbon or hydrogen). This section covers the synthesis of formamidines, aliphatic and aromatic amidines and N-acyl and N-heteroacylamidines. The second part of the review covers N-substitued amidines where at least one of the groups (R1, R2, or R3) is an atom other than hydrogen or carbon. This section of the review covers the synthesis of N-haloamidines, N-imidoylhydroxylamines (also known as amidoximes), amidrazones, and amidines with an N-sulfur, phosphorus, arsenic, antimony, silicon, or boron bond. The review also covers the synthesis of amidine complexes with transition and actinide metals, group 13 and group 14 metals.

The review uses the same structure as the earlier review, COFGT (1995) (chapter 5.19) published by Elsevier in 1995 and covers the period up to 1993 in more detail.

Amidines and N -Substituted Amidines

Magnesium bromide mediated hetero Diels-Alder cycloaddition of diene 1 (R 1 = Ph) to chiral N-acryloyl-2-oxazolidinone 4b leads to 5b as the sole adduct formed. Chiral auxiliary removal leads to enantiomerically pure 5,6-dihydro-4H- 1,3-thiazine 3 (R 2 = Bn). The selectivity of the cycloaddition is reversed under thermal or high pressure activation. The predominant diastereomeric adduct 6b is isolated in pure form after flash chromatography. For some years, studies in our laboratory have focused on the construction of the dihydro-l,3-thiazine ring, a subunit found in biologically active natural products (eg. cepharnycin C) as well as in many unnatural compounds displaying a broad range of activities (medicinal drugs, herbicids, pesticids, etc). In particular it has been shown that the hetero Diels-Alder reaction of 3-aza-4-dimethylamino-l-thia-butadienes I with acrylates 2 induced by heating 1 or by application of high pressure 2 provides a convenient and efficient route to substituted 5,6-dihydro-4H-1,3-thiazines 3, allowing for the simultaneous construction of carbon-carbon and sulfur-carbon bonds and installation of two contiguous stereogenic centers (Scheme 1).

An asymmetric route to the 5,6-dihydro-4H-1,3-thiazine skeleton via an asymmetric hetero diels-alder reaction

Easy access to substituted selenazine and selenopyran derivatives by a cycloaddition-cyclorersion process

Synthesis and reactivity of N-selenoacylamidines precursors of selenoheterocycles

Novel, diversely substituted 1-thia 3-aza butadienes have been prepared and reacted with ketene or its derivatives. Via a general (4 + 2) cycloaddition reaction, they afford functionalised 6H-1,3-thiazine 6-ones, the electrophilic properties of which are described. This cycloaddition gives rise to other reaction products resulting from the addition of two or three molecules of ketene according to the nature of the substituents.

Thia-1 aza-3 butadienes substitues: action du cetene et derives

2-Phenyl-4-dimethylamino-1-thia-3-azabutadiene and methylacrylate gave 5,6-dihydro-4H-1,3-thiazine by 4 + 2 cyclocondensation reaction at 55°C. The heterodienes configuration was established by X-Ray spectra. The Diels-Alder character of this reversible reaction was indicated by kinetic and thermodynamic parameters determined by 1H N.M.R.

Substituted 1-thia-3-aza -1,3-butadiene: diels-alder reaction with methylacrylate. determination of activation parameters

N-Protected7-amino-7-methoxy cephems are synthesised from methylN-(O-methoxycarbonylbenzoyl)methoxy(thiocarbamoyl)glycinate in two major steps: construction of the thiazine ring and subsequent closure of the β-lactam ring.

Total synthesis of N-protected 7-amino-7-methoxy cephems

The methoxylation of dihydrothazine derivatives has been carried out using t-butyl hypochlorite and lithium methoxide; a possible mechanism involving an acylimine intermediate is proposed.

M. Chehna

Papers

Thia-1 aza-3 butadienes substitues: action du cetene et derives

Substituted 1-thia-3-aza -1,3-butadiene: diels-alder reaction with methylacrylate. determination of activation parameters

Total synthesis of N-protected 7-amino-7-methoxy cephems

Simple and efficient methoxylation of 1,3-dihydrothiazine derivatives

Simple and efficient methoxylation of 1,3-dihydrothiazine derivatives