Stable and Persistent Acyclic Diaminocarbenes with Cycloalkyl Substituents and Their Transformation to β‐Lactams by Uncatalysed Carbonylation with CO

• Published in: Chemistry : a European journal Vol. 25; no. 6; pp. 1488 - 1497
• Main Authors: Wallbaum, Lars, Weismann, Daniel, Löber, Dennis, Bruhn, Clemens, Prochnow, Pascal, Bandow, Julia E., Siemeling, Ulrich
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 28-01-2019
• Subjects: Amides; amines; Antimicrobial activity; carbenes; carbonylation; Carbonyls; Cations; Chemistry; Decomposition; Derivatives; Fragmentation; lactams; NMR; Nuclear magnetic resonance; Organic chemistry; Penicillin; Selenium; selenourea derivatives; Thermal decomposition; amines; carbenes; selenourea derivatives; lactams; carbonylation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201805307

Four new acyclic diaminocarbenes (ADACs), viz. [(cyclo‐CnH2n−1)2N]2C (n=5–7) and iPr2N‐C‐N(cyclo‐C6H11)2, were synthesised by reacting the corresponding formamidinium hexafluorophosphates with NaN(SiMe3)2. Their nucleophilicities and electrophilicities were respectively judged from the 1JCH values determined for the N2CH unit of the corresponding formamidinium cations and from the 77Se NMR chemical shifts of the selenourea derivatives obtained from the reaction of elemental selenium with the corresponding ADACs. An ambiphilic profile essentially identical to that of the “Alder carbene” (iPr2N)2C was found in each case. Similar to the latter carbene, the new ADACs undergo a well‐defined thermal decomposition by β‐fragmentation, affording an alkene and a formamidine. The stabilities of [(cyclo‐CnH2n−1)2N]2C depend strongly on the value of n, following the order 6>5>7, with the latter congener being too unstable for isolation. [(cyclo‐C6H11)2N]2C shows no thermal decomposition at room temperature in solution and is thus significantly more stable than (iPr2N)2C. The stability of iPr2N‐C‐N(cyclo‐C6H11)2 is intermediate between that of (iPr2N)2C and [(cyclo‐C6H11)2N]2C, its β‐fragmentation selectively affording propene and iPrN=CH‐N(cyclo‐C6H11)2. [(cyclo‐CnH2n−1)2N]2C (n=5–7) react readily with CO under mild conditions, selectively affording trisubstituted spirocyclic β‐lactam derivatives with an antimicrobial activity spectrum similar to that of penicillin G.
Acyclic diaminocarbenes of the type [(cyclo‐CnH2n−1)2N]2C (n=5–7) are akin to the iconic “Alder carbene” (iPr2N)2C, since the cycloalkyl groups can be viewed as conformationally constrained versions of the isopropyl group. In the cyclohexyl case, this leads to a bis(dialkylamino)carbene of unprecedented thermal stability in solution. Independent of n, these carbenes react readily with CO, selectively affording spirocyclic β‐lactams with useful antibiotic properties.