The morpholine ring of the title dione, C(13)H(15)NO(3), shows a boat conformation that is distorted towards a twist-boat, with the boat ends being the two Csp(3) atoms of the ring. The benzyl substituent is in the favoured 'exo' position. In the monothione derivative, (+/-)-6-benzyl-3,3-dimethyl-5-thioxomorpholin-2-one, C(13)H(15)NO(2)S, this ring has a much flatter conformation that is midway between a boat and an envelope, with the dimethyl end being almost planar. The orientation of the benzyl group is 'endo'. The dithione derivative, (+/-)-6-benzyl-3,3-dimethylmorpholine-2,5-dithione, C(13)H(15)NOS(2), has two symmetry-independent molecules, which show different puckering of the morpholine ring. One molecule has a flattened envelope conformation distorted towards a screw-boat, while the conformation in the other molecule is similar to that in the monothione derivative. Intermolecular hydrogen bonds link the molecules in the three compounds, respectively, into centrosymmetric dimers, infinite chains, and dimers made up of one of each of the symmetry-independent molecules.

The synthesis of 3,3-dimethylmorpholine-2,5-diones 4a was achieved conveniently via the direct amide cyclization of the linear precursors of type 3, which were prepared by coupling of 2,2-dimethyl-2H-azirin-3-amines 2 with 2-hydroxyalkanoic acids 1. Thionation of 4a with Lawessons reagent yielded the corresponding 5-thioxomorpholin-2-ones 10 and morpholine-2,5-dithiones 11, respectively, depending on the reaction conditions. The structures of 3aa, 4aa, 10a, and 11a were established by X-ray crystallography. All attempts to prepare S-containing morpholine-2,5-dione analogs or thiomorpholine-2,5-diones by cyclization of corresponding S-containing precursors were unsuccessful and led to various other products. The structures of some of them have also been established by X-ray crystallography.Introduction. -In the last 30 years, we have demonstrated that the direct amide cyclization [1] is a useful method for the synthesis of cyclodepsipeptides, which contain a,a-disubstituted a-amino acids, e.g., a-aminoisobutyric acid (Aib) [2]. The combination with the azirine/oxazolone method [3] for the preparation of the linear precursors offers a convenient and efficient access to this class of compounds. For example, the reaction sequence starting with an a-hydroxy acid 1 and azirine 2a yielding compound 3 (n ¼ 1), followed by repeated hydrolysis and azirine coupling, and finally cyclization leads to cyclodepsipeptides of type 4 with 6-, 9-, 12-, and 15-membered rings [1b] (Scheme 1). Analogously, 16-and 19-membered cyclodepsipeptides are accessible from b-hydroxy acids [4]. Furthermore, cyclodepsipeptides with an alternating sequence of a-hydroxy and a,a-disubstituted a-amino acids can be prepared by coupling segments of type 3, followed by direct amide cyclization [1c] [5].The synthesis and stability of morpholine-2,5-diones (4a), which are the smallest cyclodepsipeptides, was studied already 60 years ago [6]. But only in the last couple of years have these compounds attracted increasing interest as natural products [7], biologically active compounds [8], and particularly as monomers of biodegradable polymers [9]. There are three types of cyclization leading to 4a, i.e., lactonization, lactamization, and cyclization of N-(2-bromoacetyl)glycine sodium salts (for reviews, see [10]). In the case of a,a-disubstituted glycines, a very simple and efficient protocol is the direct amide cyclization of 3 (n ¼ 1) [1b]. Surprisingly, all attempts to prepare the analogous seven-membered 1,4-oxazepane-2,5-diones 5 by the same method failed, and only the 14-membered cyclodimers were obtained [11].

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