Complex-induced proximity effects. Temperature-dependent regiochemical diversity in lithiation-electrophilic substitution reactions of N-BOC-2-azabicyclo[2.1.1]hexane. 2,4- and 3,5-methanoprolines.
[reaction: see text] Azabicycle 4 and sec-butyllithium/TMEDA afford the C(1) bridgehead alpha-lithio anion at 0 degrees C. Anion quenching with carbon dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4-methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78 degrees C these same reagents give a mixture of regioisomeric methylene and bridgehead anions whose quenching leads to mixtures of regioisomeric methylene and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.
Krow
Grant R
GR
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA. grantkrow@aol.com
Herzon
Seth B
SB
Lin
Guoliang
G
Qiu
Feng
F
Sonnet
Philip E
PE
D000900:Anti-Bacterial Agents / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D018020:Lithium Compounds / Q000737:chemistry; D008968:Molecular Conformation; D018722:Nicotinic Agonists / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D013696:Temperature
C450189:2,4-methanoproline; C471505:3,5-methanoproline; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018020:Lithium Compounds; D018722:Nicotinic Agonists; D011392:Proline