TETRAHEDRON
LETTERS
Pergamon Tetrahedron Letters 40 (1999) 6065-6068
[3+2]-Cycloaddition of Nonstabilized Azomethine Ylides, Part 9 #:
A General Approach for the Construction of X-Azabicyclo[m.2.1]alkanes in
• Optically Pure form by Asymmetric 1,3-Dipolar Cycloaddition Reactions
Ganesh Pandey*, Joydev K. Laha and A. K. Mohanakrishnan
Division of Organic Chemistry (Synthesis)
National Chemical Laboratory
Pune - 411008, India
Received 20 April 1999; accepted 29 June 1999
Abstract: A general strategy for the construction of X-azabicyclo[m.2.1]alkane frameworks in optically
pure form is reported by the asymmetric [3+2]-cycloaddition reaction of cyclic azomethine ylides with
Oppolzer's acryloyl camphor sultam. © 1999 Elsevier ScienceLtd. All rights reserved.
Several compounds possessing X-azabicyclo[m.2.1]alkane frameworks (1) viz., epibatidine t (X=7, m=
2), cocaine alkaloids 2 (X=8, m=3) and anatoxins 3 (X=9, m--4) are known to exhibit a wide variety of biological
activities. Therefore, their synthesis has occupied a prominent position as a target for organic chemists.
Although, there are many excellent approaches for the construction of these frameworks in racemic form, the
strategies related to their preparation in optically active forms are scarce. 4'5"6 As structure | encompasses an
¢t,ct'-fused pyrrolidine moiety, one attractive strategy for their preparation in optically active form may be
considered by the asymmetric 1,3-dipolar cycloaddition reaction7 of the azomethine ylides (AMY) 2, which
could be easily generated by the sequential double desilylation of 4 utilising Ag(I)F as one electron oxidant, S
with a chiral dipolarophile. Asymmetric synthesis of highly substituted pyrrolidines in varying degrees of
diastereomeric purity have been reported by 1,3-dipolar cycloaddition reactions utilising either chiral
wG" > -
R
1 2
+ / "> TMS TMS
R
3
Scheme-1
FAX: 020 -393153, Emaih pandey@ems.ncl.res.in
0040-4039/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
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