The design and synthesis of new nonproteinogenic R-amino acids is an area of current interest. 1 In particular, γ,δ-unsaturated R-amino acids have attracted attention due to their presence in natural products 2 and their usefulness as synthetic intermediates in the preparation of other R-amino acid derivatives, 3 as well as their pharmacological interest. 4 Phosphines are known to impart electrophilic character to the γ-carbon of acetylenic esters (Trost reaction). 5 This reaction has been used for C-C bond formation at carbon C-4 of ethyl 2-butynoate (1) by using carbon pronucleophiles with active hydrogen atoms. 5b Therefore, glycines that possessed an enhanced acidity of the R-CH on the basis of a suitably masked nitrogen atom (2, 3) could serve satisfactorily as pronucleophiles in the Trost reaction. Their reaction with 1 should afford the N-protected γ,δ-didehydrohomoglutamates 4, which are difficult to prepare by previously reported procedures 6 (Scheme 1). Results and DiscussionAt the onset of our study, glycine imines 2 were chosen as the pronucleophilic counterpart. 7 Heating alkyne 1 with an equimolecular ammount of 2a (R 1 ) H, R 2 , R 3 ) Ph) with 1 in toluene solution with a catalytic ammount of triphenylphosphine (5% mol) in the presence of an acetic acid-sodium acetate buffer (50% mol) 5a resulted in the recovery of the starting material together with (E)-ethyl 4-acetoxy-2-butenoate (40%). 8 The same result was obtained when the bis(methylthiomethylene)glycinate 2b (R 1 ) H, R 2 , R 3 ) SMe) or the aldimine 7,9 2c (R 1 ) H, R 2 ) p-Cl-C 6 H 4 , R 3 ) H) were used as pronucleophiles.Next, more basic reaction conditions were tested. Thus, the acetic acid-sodium acetate buffer previously used was replaced by t BuOH-KO t Bu (50% mol), which should guarantee 10 the deprotonation of glycinates 2. However, instead of the corresponding γ,δ-didehydrohomoglumates 4, the R, -didehydroglutamates 5 (Scheme 2) were the only products obtained. The results are given in Table 1.It has to be pointed out that compounds 5 were not formed in the absence of Ph 3 P and that the Michael addition of the potassium enolate of 2b with 1 in THF solution did only take place in the presence of a crown ether. 11 Therefore, the formation of the R, -didehydroglutamates 5 must be accounted for by the protonation (1) For recent references, see: (a) Burgess, K.; Ho, K.-K.; Pettit, B. M. J. Am. Chem. Soc. 1995, 117, 54. (b) Obrecht, D.; Altorfer, M.; Lehmann, C.; Schönholzer, P.; Mü ller, K. For some leading references on the most relevant methods for the synthesis of γ,δ-unsaturated amino acids, see the following. (i) Ene reaction of sulfonylimines: Yao, S.; Fang, X.; Jørgensen, K. A. J. Chem. Soc., Chem. Commun. 1998, 2547. (ii) Allylation of electrophilic glycines: Roos, E. C.; Mooiweer, H. H.; Hiemstra, H.; Speckam, W. C.; Kaptein, B.; Boesten, W. H. J.; Kamphuis, J. and references cited therein. (7) For pKa data of glycine aldimines and ketimines, see: O'Donnell, M. J.; Bennett, W. D.; Jacobsen, W. N.; Ma, Y.; Huffman, J. C. Tet...

alpha,beta-Didehydroglutamates have been diastereoselectively transformed into 6-oxoperhydropyridazine-3-carboxylic acid derivatives (OPCAs), which constitute a new class of cyclic amino acid derivatives. Acylation at N-1 renders dipeptides which show considerable conformational rigidity. Semiempirical calculations suggest that OPCAs might force peptide turns with different amplitudes depending on the substitution pattern and relative stereochemistry of the substituents of the pyridazinone ring.

In the reaction of the enolates of (Z)-N-[bis(methylthio)methylene]-α,β-didehydroglutamates with aldehydes, the retroaldolization process is faster than the aldol reaction, thus inhibiting the obtainment of the desired targets 6. However, in the presence of TMS−Cl as trapping agent, the equilibrium can be deplaced and the aldols 6 are obtained in the form of their TMS-derivatives 8. In the presence of BF3 or TBAF, either the syn or the anti adducts can be selectively obtained with good yields and diastereoselectivities.