Mannich decarboxylative

As predicted, l,2,3,4-13C-labeled acetone dicarboxylate (15) provided an intact three-carbon chain into lycopodine. It also helped to explain why two molecules of pelletierine (12) were not incorporated (Scheme 6.3) [12]. As before, lysine (6) is converted to piperideine (8) via a decarboxylation. Then a Mannich reaction of labeled 15 with 8 provides pelletierine 12. The other half of the molecule to be incorporated must be pelletierine-like (12-CC>2Na), still containing one of the carboxylates. An aldol reaction of the two pelletierine fragments and a series of transformations leads to phlegmarine 9. Oxidation of 9 involving imine formation between N-C5, isomerization to the enamine and then cyclization onto an imine (at N-C13), provides lycopodine 10. Phlegmarine 9 and lycopodine 10 are proposed as... 

The addition product of ethyl acetoacetate and methyl a-methoxyacrylate was hydrolyzed, and the resulting dicarboxylic acid was treated with dimethylamine hydrochloride and aqueous formaldehyde. The product of the Mannich reaction was decarboxylated, reesterifed, and finally treated with methyl iodide to supply quaternary salt 469 as the main product. During the above one-pot process, elimination also took place, yielding unsaturated ketone 470, which was later utilized as its hydrogen bromide adduct 471. Reaction of 3,4-dihydro- 3-car-boline either with 469 or 471 furnished the desired indolo[2,3-a]quinolizine derivative 467 as a mixture of two diastereomeric racemates. 

Dicarbonyl donors bearing a thioester has been applied in the Mannich reaction to A -tosyl imines. Ricci presented an enantioselective decarboxylative addition of malonic half thioester 37 to imine 38. In the Mannich-type addition, catalyst 36 deprotonates the malonic acid thioester followed by decarboxylation to generate a stabilized thioacetate enolate. This stabilized anion reacts with facial selectivity to the imine due to steric-tuning from 36 [47] (Scheme 8). 

The construction of a quaternary a-stereocenters was demonstrated in the 117-catalyzed Mannich addition [72] of methylcyclo-pentanone-2-carboxylate to N-Boc-protected aromatic aldimines and furnished the adducts 1-3 in 70-97% yield, with good ee values (85-87%) and diastereoselectivities (Scheme 6.115). The authors exemplified the synthetic utility of the protocol by a simple racemization-free decarboxylation of the Mannich adduct of N-Boc benzaldimine and dimethyl malonate to obtain the respective N-Boc-protected p-amino ester (68% yield/89%... 

To get conjugate addition we might use a -ketoester 18 or an enamine for the enolate and we might carry out the reaction using the Mannich salt 19 so that the elimination will be caused by the same base that makes the enolate. Ester hydrolysis and decarboxylation of 20 would give 1. 

Fig. 91. Deaminomethylation with decarboxylation of carboxyl-ated Mannich ba.<>es.

The Mannich bases investigated are acctoacetic and malonic acid derivatives, Y-carboxyglutamic acid included. - Compounds having the lactone structure give preferably decarboxylation of the ester groups not involved in the lactone ring. - ... 

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