Solutions to Problems
In this section solutions are given to the problems delineated in the previous chapters. The answers given are by no means the only valid answers; rather they serve as examples of a suitable solution.
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Solutions to Problems
In this section solutions are given to the problems delineated in the previous chapters. The answers given are by no means the only valid answers; rather they serve as examples of a suitable solution. 2.1 Brevicomins The 1,2-diol unit allows a retrosynthetic disconnection between the two oxygen functionalities using an umpoled synthon, preferably on the side of the smaller fragment [1, 2, 3] (Scheme 13.1). OH
OH
OH
O
PGO
OH
O
M
O
O
Scheme 13.1 Functional group oriented retrosynthesis of brevicomin
Using an alkene as profunctionality for the diol unit opens possibilities for skeletal bond formation in the vicinity of the double bond (cf. Sect. 3.1, pages 55–56) [4, 5] beyond focusing solely on the vicinity of the carbonyl group (Scheme 13.2). a
d
d
O
COOR
Br
O
a
O
Cu
O
Scheme 13.2 Retrosynthesis of brevicomin considering a profunctionality
R.W. Hoffmann, Elements of Synthesis Planning, c Springer-Verlag Berlin Heidelberg 2009 DOI 10.1007/978-3-540-79220-8 13,
207
208
13 Solutions to Problems
2.2 Indolizidines The 1,3-distance of functional groups can be reached using synthons with natural polarity. The 1,2- and 1,4-distances indicated would require construction reactions using one umpoled synthon (Scheme 13.3). 1,2 1,4
PGO N
1,3
O 1,2
Scheme 13.3 Distance relationships between functional groups in an indolizidine target
Disconnection A in Scheme 2.65 suggests the following polarity patterns, each of which requires an umpoled synthon (Scheme 13.4). PGO
PGO N
N
O
63
O 64
Scheme 13.4 Polar bond disconnection in an indolizidine target
Situation 63 could be readily attained by an imine alkylation (Scheme 13.5).
PGO
Cl O H 2N
PGO Cl a
Cl N
N PGO
d
PGO
PGO
N
PGO N
N
O
Scheme 13.5 Proposed synthesis of an indolizidine target
In order to stabilize a carbanion in structure 63 an extra substituent such as a sulfonyl group would be required (Scheme 13.6) [6].
13 Solutions to Problems O
SO2Ph
PGO
209 SO2Ph
PGO
NH2
NH
SO2Ph
PGO
PGO
Cl
N
SO2Ph
PGO N
OH
d
SO2Ph a
N
O
PGO
PGO N
O
N
O
O
Scheme 13.6 Proposed synthesis of an indolizidine target
Bond A in Scheme 2.65 could also be considered to be formed in a (nonpolar) ring closing metathesis reaction (Scheme 13.7). PGO
PGO NH2
Pd(II) or other metals
PGO
PGO
PGO
RCM NH
N
N
O
N
O
O
Scheme 13.7 Proposed synthesis of an indolizidine target
A disconnection at bond B in Scheme 2.65 leads to the following polarity patterns, again involving umpoled building units (Scheme 13.8). RO
RO N
N
O
O
66
65
Scheme 13.8 Polar bond disconnection of an indolizidine target
In order to generate the carbanion in structure 65, the use of a stabilizing substituent (PhSO2 ) is indicated. The cationic part is easily identified as an iminium ion (Scheme 13.9). SO2Ph
PGO
SO2Ph
PGO
O
O
N
N Cl
O
SO2Ph
PGO
O
N O
O
Scheme 13.9 Proposed synthesis of an indolizidine target
PGO
PGO N
O
N
O
210
13 Solutions to Problems
In order to guarantee deprotonation in α-position to t
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