Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume 9, Issue 5, Pages 651-659Publisher
AMER CHEMICAL SOC
DOI: 10.1021/op050087e
Keywords
-
Categories
Funding
- NIGMS NIH HHS [R01 GM036238, R01 GM036238-20] Funding Source: Medline
Ask authors/readers for more resources
2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin (1) is a crucial building block in the rational synthesis of chlorins and oxochlorins. The prior five-step synthesis of 1 from pyrrole-2-carboxaldehyde (2) employed relatively simple and well-known reactions yet suffered from several drawbacks, including limited scale (<= 0.5 g of 1 per run). A streamlined preparation of 1 has been developed that entails four steps: (i) nitro-aldol condensation of 2 and nitromethane under neat conditions to give 2-(2-nitrovinyl)pyrrole (3), (ii) reduction of 3 with NaBH4 to give 2-(2-nitroethyl)pyrrole (4), (iii) Michael addition of 4 with mesityl oxide under neat conditions or at high concentration to give gamma-nitrohexanone-pyrrole 5, and (iv) reductive cyclization of 5 with zinc/ammonium formate to give 1. Several multistep transformations have been established, including the direct conversion of 2 -> 1. The advantages of the new procedures include (1) fewer steps, (2) avoidance of several problematic reagents, (3) diminished consumption of solvents and reagents, (4) lessened reliance on chromatography, and (5) scalability. The new procedures facilitate the preparation of I at the multigram scale.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available