Ynolates are the triple-bond version of enolates. In contrast to the well-established chemistry of enolates, 1 only scattered examples of the ynolate chemistry have been reported so far. 2-6 The first example was reported in 1975 by Schöllkopf, who succeeded in the generation of lithium phenylethynolate by extrusion of benzonitrile from 5-lithio-3,4-diphenylisoxazole. 2 Since then, various routes to ynolates have been developed by Kowalski, 3 Stang, 4 Julia, 5 and Rathke. 6 Nevertheless, ynolates received only little attention as synthetic reagents because of lack of convenient methods of their generation. The reactions of ethynolates with aldehydes, 2a,b,3a ketones, 2a,b,3a and imines 2c to give the corresponding -lactones or -lactams have been studied. A silylethynolate 6 is quite attractive because a silyl group can be converted into other functional groups in various ways. 7 In this paper a unique access to and the new reactions of the silylethynolate will be described.Our new route to the lithium silylethynolate involves the acyllithium (R-CO-Li) chemistry. Two different approaches have been developed to utilize the highly reactive intermediate RCOLi. The one involves in situ intermolecular trapping of the acyllithium as studied by Seyferth 8 and others. 9 The other developed by us involves intramolecular conversion of the unstable acyllithium to a more stable but still useful intermediate such as enolate. 10 Now we have studied the reaction of a lithiated silyldiazomethane 1 with carbon monoxide expecting that the extrusion of dinitrogen from an acyllithium 2 should provide the driving force for a clean reaction. This is the case. The results not only provide a unique entry to a lithium ynolate having a silyl group 6 4 (Scheme 1) but also lead to a unique synthetic operation that enables "ketenylation". 11 To a THF-hexane solution of trimethylsilyldiazomethane 12 was added a hexane solution of BuLi (1.2 equiv) at -78°C and the mixture was stirred at that same temperature for 1 h. Then, the mixture was exposed to an atmospheric pressure of carbon monoxide at -78°C for 2 h. Addition of 1.

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Diastereoselective conjugate addition of lithium (S)-Nallyl-N-a-methylbenzylamide to a,b-unsaturated esters or Weinreb amides, followed by ring closing metathesis is used to afford the cyclic b-amino acids (S)-homopipecolic acid and (S)-homoproline and the amine (S)-coniine in high ee.The synthesis of conformationally constrained amino acid derivatives has received much recent attention due to their ability to act as conformational probes when incorporated into peptides and peptidomimetics. 1 Asymmetric approaches toward these targets have largely focused upon the production of novel a-amino acid derivatives, 2 with the preparation of homochiral cyclic b-amino acids relatively less studied, although these attractive synthetic targets have previously been constructed by homologation of a-amino acids, 3 intramolecular ring closure 4 and stereoselective hydrogenation. 5 Previous investigations from our laboratory have shown that the highly diastereoselective conjugate addition of homochiral lithium N-alkyl-N-amethylbenzylamides to a range of a,b-unsaturated esters and subsequent N-deprotection offers an efficient route to the asymmetric synthesis of b-amino acid derivatives. 6 In order to extend the utility of this methodology, a protocol involving functionalisation, rather than deprotection, of the N-alkyl groups of the chiral lithium amide used in the conjugate addition reaction was desired. The N-allyl functionality contained within (S)-N-allyl-N-a-methylbenzylamide 1 was selected for this purpose and we describe herein the use of ring closing olefin metathesis 7 for the synthesis of cyclic b-amino acids and amines (Figure). 8The initial target for this methodology was the synthesis of (S)-homopipecolic acid 6. 9 Thus, conjugate addition of lithium (S)-N-allyl-N-a-methylbenzylamide 1 to (E,E)-methyl heptan-2,5-dieneoate 2 gave (3S,aS)-methyl 3-(Nallyl-N-a-methylbenzylamino)hept-5-enoate 3 in 69% yield and >95% de. 10 Treatment of b-amino ester 3 with Grubbs' ruthenium alkylidene catalyst 11 furnished cyclic N-protected b-amino ester 4 in 49% yield and in >95% de, indicating that no epimerisation had taken place during the ring closing metathesis protocol. N-deprotection via catalytic hydrogenation afforded b-amino ester 5 in 93% yield and >95% ee, 12 with subsequent ester hydrolysis giving (S)-homopipecolic acid 6 {[a] D 26 +24.0 (c 0.87, H 2 O); lit. 13 [a] D +22.

A silylynolate, generated via the carbonylation of lithium silyldiazomethane, was reacted with N-tosyl aziridines to produce various five-membered lactams in good yields. The key step of this reaction involves the ring-opening ketenylation of aziridines by the silylynolate. The reaction proceeded in a highly stereoselective manner, and ketenylation took place at the less hindered carbon. When treated with aldehydes prior to protonation, the alpha-silylated lactam enolates gave alpha-vinylidene gamma-lactams. These reactions represent a unique path to the generation of and for controlling the reactivity of a rare class of reactive intermediates, namely, acyllithium derivatives and ynolates.

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