Synthesis of α‐Cyanoenamines by Cyanation of α‐Bromoimmonium Bromides and Dehydrobromination of β‐bromo‐α‐(dialkylamino)nitriles

Abstract

The reaction of a-bromoimmonium bromides 4 with potassium cyanide in dimethylformamide gave rise to P-bromo-a-(dia1kylamino)nitriles 5, which were dehydrobrorninated in various basesolvent systems to afford (E)-and (Z)-a-cyanoenamines 2. An adaption of a previously published preparation of a-cyanoenamines starting from aldehydes oia enamines led to an improved, efficient and fast synthesis of the title compounds. Synthese von a-Cyanenaminen durch Cyanierung von a-Bromimmonium-bromiden und Dehydrobromierung von p-Brom-a-(dialky1amino)nitrilenDie Reaktion der a-Bromimmonium-bromide 4 mit Kaliumcyanid in Dimethylformamid gibt P-Brom-a-(dialky1amino)nitrile 5, die in verschiedenen Base-Losungsmittel-Systemen zu (E)-und (2)-a-Cyanenaminen 2 dehydrobromiert werden. Eine Modifizierung einer kiirzlich veroffentlichten Synthese von a-Cyanenaminen 2 aus Aldehyden iiber Enamine fiihrte zu einer verbesserten und schnellen Methode fur die Darstellung der Titelverbindungen. a-Cyanoenamines (1, 2) are a group of functionalized olefins which contain a sp2 carbon atom, geminally substituted with an electron-withdrawing and electrondonating substituent.Especially during the last decade efforts have been undertaken for the synthesis of a-cyanoenamines, which were shown to be valuable synthons in synthetic organic chemistry (vide infra). A variety of synthetic methods are now available to synthesize secondary a-cyanoenamines 1 and tertiary a-cyanoenamines 2. Secondary a-cyanoenamines 1 are synthesized by reaction of a-chloroaldimines with potassium cyanide* -4, or, to a lesser extent, by dehydrohalogenation of appropriate P-halo-a-(alky1amino)nitriles -').Only in the former case are secondary a-cyanoenamines 1 generally accessible, while in the latter case an additional isomerism to the tautomeric imidoyl cyanides prohibits isolation of pure a-cyanoenamines.

Organocatalytic Enantioselective α-Hydroxymethylation of Aldehydes: Mechanistic Aspects and Optimization

“…More recently, Hayashi and co-workers have reported a related enantioselective α-hydroxymethylation of aldehydes catalyzed by the related 3,5-bistrifluoromethylaryl prolinol in comparable yields and enantioselectivity, but with the opposite sense of asymmetric induction . In contrast to our protocol, where the enantioselectivtiy is apparently controlled by the steric bulk of the diaryl- and trialkylsilyloxy- substituent of the prolinol, the catalyst systems employed by Córdova and Hayashi apparently impart enantioselectivity through hydrogen bonding with the carboxylic acid or alcohol functionality of the catalyst serving to orient the formaldehyde electrophile syn to the α substituent of the proline in the transition state. , …”

“…To investigate the feasibility of the foregoing catalytic cycle, we began with the reaction of the preformed enamine 5 , derived from pyrrolidine and isovaleraldehyde with varying amounts of 37% aq formaldehyde (formalin) . Our preliminary experiments demonstrated that use of ∼3.0 equiv of formalin in a variety of solvents followed by the reduction of crude products with sodium borohydride (NaBH 4 ) provided substantial amounts of allylic alcohol 6 rather than the desired α-hydroxymethylation product 7 accompanied by trace amounts of alcohol 8 derived from the self-condensation of isovaleraldehyde followed by dehydration (1.5:1:trace of 6 : 7 : 8 ) .…”

Fluorocyanation of Enamines

“…The overall result of this stepwise reaction corresponds to fluorocyantion of the CC bond. It should be pointed out that in the literature addition reactions of cyanogen fluoride to alkenes have not been reported …”

Captodative aminoalkenes

“…There are also other examples where the resulting 2-amino-3halopropiononitriles 10 were subjected to dehydrohalogenation to give the corresponding 1-cyanoenamines 2a, including those with the unsubstituted, 39 mono- 40 or disubstituted amino group. 41,42 For these reactions, Et 3 N 32 ± 36, 39 ± 41 or NaOH 31 are the reagents of choice.…”