Cyclopropan‐Derivate, 2. Selbst‐Acylierung der α‐Alkyl‐γ‐lactone zu Herstellung von Bis(1‐alkylcyclopropyl)ketonen über Spiro[4.4]acetale

Neuner

2018

Helvetica Chimica Acta

Self Cite

The title compound (1) was chosen as a model for the α/α′‐regioselectivity of deprotonation and subsequent alkylation adjacent to the C=N bond. With the bulky base lithium N,N‐diisopropylamide (LDA) as a catalyst, the one‐pot deprotonation steps can be performed through titration with methyllithium, using gas‐volumetric observation of the liberated methane. In the first step with ensuing methylation by iodomethane, the primary product is born at −40 °C in its metastable (Z) configuration (kinetic control) and may be either isolated or converted in situ at 30 °C into its thermodynamically favored (E)‐isomer via cis to trans stereoinversion at the N‐atom. Being slow enough on the laboratory time scale, this stereoinversion process can serve to control the regioselectivity of the second deprotonation/alkylation sequence as follows. The α,α′‐products are formed from the intermediate (Z)‐imine, whereas α,α‐products result from the intermediate (E)‐imine; in either case, syn deprotonation (cis to tBu at nitrogen) by LDA is apparently disfavored by the tBu group, so that anti deprotonation becomes obligatory. If a third one‐pot deprotonation step is too slow with LDA, it may be performed with the stronger base butyllithium/HMPA which, however, reacts regio‐unselectively. Regioselective one‐pot, LDA‐catalyzed deprotonation with alkylation by oxiranes (alone, or alternatingly with iodomethane) opens a short access to spiro‐[2.4]heptan‐4‐ones.

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…13 C‐NMR (CDCl 3 , 20.15 MHz): 31.14 (2 × CH 2 ); 31.50 (2 × CH 2 ); 47.7 (2 × CH); 69.2 (2 × OCH 2 ); 128.8 (1 × quat C); as in Ref. . Anal.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Regioselective Dialkylations of N‐(tert‐Butyl)iminocyclopentane via Deprotonating One‐Pot Procedures

Neuner

2018

Helvetica Chimica Acta

Self Cite

Cyclopropan‐Derivate, 3. (1‐Alkylcyclopropyl)ketone durch Acylierung von α‐substituierten γ‐Lactonen

Böhrer

1990

Chem. Ber.

Self Cite

Cyclopropane Derivatives, 3').-(1-Alkylcyclopropy1)ketones by Acylation of a-Substituted y-Lactones The 2-acylation of 2-substituted 4-butanolides 2 is moderately sensitive to steric crowding, whereas the subsequent ringopening of 2-acyl-2-alkyl-4-butanolides 4, 11 to give y-chloro ketones 6, 12 by chloride-transferring acid derivatives becomes difficult with bigger lactone substituents. Similar observations pertain to the preparation of y-chlorobutanoyl chlorides 10 from 2-alkyl-4-butanolides 2. lb,cAcyclische Esterenolate reagieren rnit Carbonsaurechloriden glatt zu p-Oxoestern'6). Da iiber die entsprechende Acylierung von m-substituierten Lactonen anscheinend wenig bekannt ist '7,38), fiihrten wir zunachst Modell-Acylierungen der Lactone 2a2) und 2c rnit Pivalinsaurechlorid'6) durch, um den EinfluQ kleiner und groI3er Substituenten R' auszuloten. Von den rnit LDA hergestellten Lactonenolaten 3a,c ergab nur 3a glatt das spektroskopisch eindeutig chaChem. Ber. 123 (1990)

Pivaloylmetals (tBu‐COM: M=Li, MgX, K) as Equilibrium Components

Böhrer

Schubert

et al. 2012

Chemistry A European J

Short-lived pivaloylmetals, (H(3)C)(3)C-COM, were established as the reactive intermediates arising through thermal heterolytic expulsion of O=CtBu(2) from the overcrowded metal alkoxides tBuC(=O)-C(-OM)tBu(2) (M = MgX, Li, K). In all three cases, this fission step is counteracted by a faster return process, as shown through the trapping of tBu-COM by O=C(tBu)-C(CD(3))(3) with formation of the deuterated starting alkoxides. If generated in the absence of trapping agents, all three tBu-COM species "dimerize" to give the enediolates MO-C(tBu)=C(tBu)-OM along with O=CtBu(2) (2 equiv). A common-component rate depression by surplus O=CtBu(2) proves the existence of some free tBu-COM (separated from O=CtBu(2)); but companion intermediates with the traits of an undissociated complex such as tBu-COM & O=CtBu(2) had to be postulated. The slow fission step generating tBu-COMgX in THF levels the overall rates of dimerization, ketone addition, and deuterium incorporation. Formed by much faster fission steps, both tBu-COLi and tBu-COK add very rapidly to ketones and dimerize somewhat slower (but still fairly fast, as shown through trapping of the emerging O=CtBu(2) by H(3)CLi or PhCH(2)K, respectively). At first sight surprisingly, the rapid fission, return, and dimerization steps combine to very slow overall decay rates of the precursor Li and K alkoxides in the absence of trapping agents: A detailed study revealed that the fast fission step, generating tBu-COLi in THF, is followed by a kinetic partitioning that is heavily biased toward return and against the product-forming dimerization. Both tBu-COLi and tBu-COK form tBu-CH=O with HN(SiMe(3))(3), but only tBu-COK is basic enough for being protonated by the precursor acyloin tBuC(=O)-C(-OH)tBu(2) .