L-pipecolinic acid

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

Formamides derived from L-pipecolinic acid act as Lewis base organocatalysts for reduction of A-arylimines with trichlorosilane, giving yields and ees in the high 90s for a wide range of imine substrates.54... 

L-Pipecolinic acid-derived formamides have been developed as highly efficient and enantioselective Lewis basic organo-catalysts for the reduction of IV-arylimines with trichlorosilane. High isolated yields and enantioselectivities up to 96% are obtained under mild conditions with a large substrate spectrum.365... 

Employing a flow rate of 1 (il min 1 and a residence time of 0.86 min, the authors obtained 87% conversion of L-lysine (191), exhibiting 22% selectivity for pipecolinic acid and 14% yield of L-pipecolinic acid 190. To demonstrate the TCM s efficiency, the authors also performed the reaction in batch employing 2wt% Pt-loaded Ti02 particles, which afforded the same surface to volume ratio of catalyst as calculated to be within the TCM, whereby a reaction time of 60 min afforded analogous results. The authors concluded that the increased reaction efficiency observed within the TCM was attributed to the efficient irradiation of the reaction mixture however, for a true comparison they noted that measurement of the quantum yield of each system would be required. 

Scheme 55 Photocatalytic synthesis of L-pipecolinic acid 190 and D-pipecolinic acid 192.

Kitamori and coworkers reported the use of a Ti02-modified microchannel chip reactor (TMC, Pyrex glass chip, having branched channels 770 pm wide and 3.5 pm deep) for photocatalytic redox-combined synthesis of L-pipecolinic acid from L-lysine (Scheme 4.31) [45], Although both batch and microflow systems gave comparable yield and enantiomeric excess of the product, the conversion rate was significantly higher for the microflow reactor than for the batch system. 

Baikiain (172), (— )-4,5-dehydro-L-pipecolinic acid, was isolated from the African tree Baikiaea plurijuga.162 Catalytic hydrogenation of 172 gave l-( — )-pipecolinic acid (173) A-carboxymethyl-L-aspartic acid (174) was obtained from 172 by ozonolysis.162... 

Ohtani and coworkers [409-413] found photocatalytic one-step synthesis of L-pro-line and L-pipecolinic acid from L-ornithine and L-lysine using aqueous semiconductor suspensions. 

An example of a photochemical cyclization was reported by Takei et al. [92], who demonstrated the synthesis of L-pipecolinic acid (160) from an aqueous solution of L-lysine (161), as illustrated in Scheme 6.42. To achieve this photocatalytic transformation, the authors fabricated a Pyrex micro reactor in which the channel cover plate was coated with a 300nm layer of anatase Ti02 (100 nm particles), to afford a titania-coated micro reactor (TCM) the titania film was subsequently loaded with platinum (0.2 wt%), by photodeposition, to enable the TCM to be used... 

As the first chlorides of their kind, their ability to acylate L-proline and L-pipecolinic acid derivatives, which are more difficult to acylate than ordinary amino acids, was investigated in detail. Uniformly good to excellent yields of the expected products were obtained in each case. ... 

Sun and co-workers [29] has also made a great contribution to this field, developing novel class of catalysts for the enantioselective hydrosUylation of ketoimines. He reported (5)-proline-derived catalyst obtaining high yields and moderate to high enantioselectivities. Moreover, he developed the first catalyst derived from (L)-pipecolinic acid, able to promote the reaction with high yields and enantioselectivity and, for the first time, the reduction of aliphatic ketimines [30] (Scheme 15.6). This work was also the first to demonstrate the independence of the ketimine geometry on the selectivity of the reaction. 

T. Kitamori, G. Takei, H.B. Kim, Photocatalytic redox-combined systhesis of L-pipecolinic acid with titania modified microchannel chip, Catal. Commun. 2005, 6, 357-360. 

Takei, G., Kitamori, T. and Kim, H.B. (2005). Photocatalytic redox-combined synthesis of L-pipecolinic acid with a titania-modified microchannel chip. Catalysis Communications, Vol. 6, pp. 357-360. 

Recently, Kibayashi reported the total synthesis of (+)-homopumiliotoxin 223G (31a, Scheme 8). A-CbZ-L-Pipecolinic acid was converted into compound 32, which was treated with Ph3SiH in the presence of Et3B to afford vinylstannanes 33a and 33b in a ratio of 3.6 1. Treatment of vinylstannane 33a with NIS gave vinyl iodide 34, which was subjected to Pd-catalyzed lactonization to give lactone 35 in quantitative yield. From this compound, they succeeded in the total synthesis of homopumiliotoxine 223G (31a). 

Sun and co-workers developed a novel Lewis basic organocatalyst 86 (Scheme 31), easily synthesized from commercially available L-pipecolinic acid. The catalyst 86 promoted the reduction of IV-aryl ketimines 85 with HSiCl3 2 in high yield and... 

Scheme 31 Model L-pipecolinic acid derived A -formamide catalysts 86-88...

Takei and coworkers [8] demonstrated the synthesis of L-pipecolinic acid (11) from an aqueous solution of i-lysine (12) (Scheme 6.5). To achieve this photochemical... 

Based on the previous discovery that trichlorosilyl derivatives could be activated by N-formamide-based Lewis base organocatalysts. Sun et al. designed a series of novel catalysts (82 and 83) derived from L-pipecolinic acid, which features a six-membered ring frame rather than 72 and 73, which have a five-membered ring derived from L-proUne [50]. Surprisingly, both 82 and 83 proved to be superior catalysts for the hydrosilation of N-aryl ketimines. Both enantioselectivities and... 

Scheme 8.12 (a) Photocatalytic transformation of primary amines to secondary amines via C-N coupling reaction on Pt/Ti02 [113]. (b) Photocatalytic transformation of L-lysine to L-pipecolinic acid via C-N coupling reaction on Ti02 [110]... 

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