Synthesis of I-Lactams

A new protocol for the stereoselective synthesis of (i-lactams [213] has been reported to be performed by a conrotatory ring closure of l-halo-3-aza-4-alkyl-l, 3-dienes, previously prepared by Staudinger methodology, (for the synthesis and chemistry of /V-silyl imines see [214] for [2+2] cycloaddition of /V-silyl imines and ketenes see [215]) in refluxing toluene (Scheme 96). 

The Lectka group also reported an exciting development in this organocatalytic synthesis of /I-lactams - application of the concept of column asymmetric catalysis [50, 51]. This concept is based, e.g., on two jacketed columns linked together (Scheme 5.32) [50]. The top column is packed with the polymer-supported dehy-drohalogenation agent BEMP, which produces the desired ketenes, in high purity, from acid chlorides. In addition to this in-situ-formed pure ketene, an imine is... 

In addition to the studies mentioned above, chiral alcohols have been used as H-bonding catalysts in a vinylogous aldol reaction of Chan s diene with aldehydes [73], in an enantioselective Strecker reaction [74], and in the enantioselective addition of aza-enamines to imines [75]. Taddol has also found use as a memory of chirality enhancer in the stereoselective synthesis of (i-lactams from amino acid derivatives [76, 77]. 

Evans DA, Sjorgen EB. The asymmetric synthesis of (i-lactam antibiotics-I. apphcation of chiral oxazolidones in the Staudinger reaction. Tetrahedron Lett. 1985 32 3783-3786. 

Ratcliffe, R.W. and Reuther, W., Total synthesis of P-lactam antibiotics. I. a-Thioformamidodiethylphosphonoacetates, Tetrahedron Lett., 4645, 1973. 

Hanusch-Kompa C, Ugi I (1998) Multi-component reactions 13 synthesis of [gamma]-lactams as part of a multiring system via Ugi-4-centre-3-component reaction. Tetrahedron Lett 39(18) 2725-2728... 

Solid phase-transfer reactions.2 A strong base ion-exchange resin (Duolile A-109, Diamond Shamrock) can serve as a solid phase-transfer catalyst for synthesis of /1-lactams (3) from oc-methyl-a./l-dibromopropionyl chloride (I) and an amino acid (2) U / 9, 360). 

Si-Lactams. The synthesis of /5-lactams employing organoiron complexes as intermediates (8, 454-455) has been extended to the preparation of bicyclic lactams, in particular to the new carbopenams. A synthesis of 2-methylcarbopenam (1) is shown in equation (I). 

Lactams.1 A new synthesis of 0-lactams involves oxidative coupling of dianions of acyclic amides such as 1, prepared as shown from p-anisidine (equation I). The amide 1 is converted into the dianion by BuLi (2 equiv.) and DABCO or by t-... 

Palomo, C. Aizpurua, J. M. Ganboa, I. Oiarbide, M. Asymmetric Synthesis of P-Lactams by Staudinger Ketene-Imine Cycloaddition Reaction, Eur. J. Org. Chem. 1999, 3223-3235. 

Chiral fi-lactams. The synthesis of /1-lactams from ketene silyl acetals and Schiff bases (8, 484-485) results in asymmetric induction at C4 in the range 44-78% when optically active Schiff bases are used. An example is shown in equation (I). 

The Staudinger reaction, i.e. the [2+2] ketene-imine cycloaddition, is the most frequently employed procedure of synthesis of the azetidin-2-one nucleus. Base-promoted cyclization of suitable linear substrates is another frequently employed procedure. We wish to report the electrochemical methodologies of synthesis of P-lactams, according to both procedures, and the possible utilization of RTILs (as solvents and/or as parent of intermediates). 

Coyne AG, Miiller-Bunz H, Guiry PJ (2007) The asymmetric synthesis of p-lactams HETPHOX/Cu(I) mediated synthesis via the Kinugasa reaction. Tetrahedron-As5mmietr 18 199-207... 

Sotgiu G, Chiarotto I, Feroci M, Orsini M, Rossi L, Inesi A (2008) An electrochemical alternative strategy to the synthesis of P-lactams part 3. Room-temperature ionic liquids vs molecular organic solvents. Electrochim Acta 53 7852-7858... 

Largely stimulated by the synthesis of 3-lactam antibiotics, there have been widespread investigations into the stereochemical aspects of imine condensations, mainly involving reactions of enolates of carboxylic acid derivatives or silyl ketene acetals. In analogy to the aldol condensation, stereoselectivity of imine condensations will be discussed in terms of two types in this chapter (i) simple dia-stereoselectivity or syn-anti selectivity, when the two reactants are each prochiral (equation 12) and (ii) diastereofacial selectivity, when a new chiral center is formed in the presence of a pre-existing chiral center in one of the reactants (e.g. equation 13). The term asymmetric induction may be used synonymously with diastereofacial selectivity when one of the chiral reactants is optically active. For a more explicit explanation of these terms, see Heathcock s review on the aldol condensation. ... 

Synthesis of dialkyl sulfides (additives for lubricants, stabilizers for photographic emulsions) Synthesis of spiro derivatives of tetrahydrothipene, a characteristic fragment of many alkaloids I Synthesis of j3-lactams... 

Synthesis from i-ascorbic acid L-Ascorbic acid has been used as a chiral starting material for the synthesis of 3-lactams (Scheme 15). It was converted into... 

Lactams are cyclic amides and they are reduced by LiAlHq to the cyclic amine. The reduction of a typical lactam such as 2-pyrrolidinone derivative 36 presumably proceeds via initial formation of the a-amino alcohol (37), followed by elimination to an iminium salt (38), and then reduction by hydride to give the amine (39). This reaction is very useful in the synthesis of alkaloids, as seen in the reduction of 40 to 41 in 88% yield as part of Overman s synthesis of (-i-)-aloperine. O The lactam nitrogen is significantly less basic than the corresponding amine and cyclic amines are often protected as the lactam. The amine is then unmasked late in the synthetic sequence by hydride reduction. 

Davies examined the same reaction.He found that when using an excess of Et2Al adducts of the enolate, the diastereoselectivity ratio became > 100 1. Further, if Cu(I) was used as counter ion the opposite stereochemistry was obtained.Moreover both Davies and Liebsekind used this chiral iron auxiliary in a stereoselective synthesis of S-lactams. " " Liebeskind reported that chiral iron enolate complex condensed with imines in the presence of Et2Al counter ion to give two isomers with a ratio up to 20 1. Oxidation with I2/R3N produced the racemic jS-lacatms (Scheme 3.9)... 

The synthesis of a-lactams from a-haloamides can be accomplished using i-BuOK or KOH/18-crown-6. Alternatively, using sodium hydride with 15-crown-5 ether provided the products in superior yields while reducing the necessary reaction time (eq 38). ... 

For reviews on the synthesis of p-lactams, see a) Sheehan JC, Corey EJ (1957) Org Reac 9 Chapt 6 b) Mukerjee AK, Srivastava, RC Synthesis 1973 373 b) Isaacs NS (1976) Chem Soc Rev 76 181 c) Bose AK, Manhas MS (1976) Lect Heterocycl Chem 3 43 d) Mukerjee AK, Singh AK (1978) Tetrahedron 34 1731 e) Koppel GA (1983) In Hassner A (ed) Small ring heterocycles-azetidines, p-lactams, diazetidines and diaziridines, Wiley, New York, Chapt 2 f) From azetidiniminium salts, see Ghosez L, Bogdan S, Ceresiat M, Frydrych C, Brynaert J, Portuguez MM, Huber I (1987) Pure Appl Chem 59 393... 

The acid chloride—imine method [48] has resulted in numerous new 0-lactams during the past decade [49,50]. In the attempted synthesis of I-aza-octam analogues of cephalosporins, the Macetylated tetrahydropyrimidines (89) were used as imine components [46] and different acid chlorides as ketene precursors in the presence of Iriethylamine (TEA). 

I. Ugi and J. Geller The selective Cleavage of Carbon-amide Groupsy and the Synthesis of B-Lactam Antibiotics by Four Component Condensation Chem. Scripta 22 (1983) 85-89. 

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