Problema 14 - Ciclopropani

14-1. The heats of combustion of cyclopropane and cyclohexane are 697.1 and 658.6 kJ mol-1 per CH2 unit, respectively.
Which one is more thermally stable? Please give a choice based on the structural analysis of cyclopropane and cyclohexane,
which of the following factors is not associated with this difference in thermal stability?

(a) Hydrogen bond (b) Angle strain

(c) Torsional strain (d) Van der Waal’s force
C

105 o
60 o
C C

3 atomi de C – structura plană

Legături curbate (de tip banană)
Unghiul de legătută - 60° vs. optim 109.5°, Formula de proiecție Newman a ciclopropanului

Tensiunea totala a ciclopropanului:

• tensiune angulară;
• tensiune torsională (conformațională sau Pitzer);
• tensiune transanulară (Van der Waal’s sau Prelog);
14-2 Substituted cyclopropanes can be obtained by the reaction of alkenes with a sulfur ylide. For example, D-A cyclopropane 1
can be prepared by the following reaction:

Please assign all the peaks to the corresponding hydrogen atoms.

1H NMR (400 MHz, CDCl3) δ:
7.23 (2H, d, J = 8.0 Hz),
7.19 (2H, d, J = 8.0 Hz),
3.77 (3H, s), 3.39 (3H, s),
3.14 (1H, dd, J= 9.0 and 8.1 Hz),
2.12 (1H, dd, J = 8.1, 5.1 Hz),
1.74 (1H, dd, J = 9.0, 5.1 Hz).
14-3 The formal cycloaddition reactions of D-A cyclopropanes with unsaturated bonds are highly regioselective. Draw the
structures of products 2-6 for the following reactions (The stereochemistry is ignored).
14-4 The intramolecular cycloaddition reaction of D-A cyclopropane 6 can be promoted by Lewis acid Yb(OTf)3, to form the
parallel-cycloaddition (IMPC) product 7 and cross-cycloaddition (IMCC) product 7’. Draw the structures of the two possible
intermediates C and C’.
14-5 .Lewis acid-catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with carbonyls provided an
efficient construction of bridged oxa-[n.2.1] skeletons, and successfully applied it to the formal total synthesis of platensimysin.
Draw the structures of compounds 8-12.
Br Br O
Li O
CHO O
pTsOH O
n-BuLi, Et2O O CH2=C(CH3)CH2Cl
O
HOCH2CH2OH
OMe OMe
OMe
OMe
8

COOMe
COOMe [Me3S=O]+I-, NaH
CHO
1M HCl, THF CH2(COOMe)2, Py COOMe
reflux COOMe

OMe
OMe
OMe
9 10

O COOMe COOMe
COOMe COOMe
COOMe O
OsO4/NaIO4
Sc(OTf)3 decarboxilare O
-CH2O Platensimycin
OMe
Chemical Formula: C17H20O6 OMe
Chemical Formula: C17H20O6 OMe
11 12
Problema 19

Trans-tioesterificare Rearanjare prin transfer acil S N

Native chemical ligation
O SH
O HS +/- R-SH H2N O
H2N S H2 N OH
S R OH N
H2 N OH H
H2N O
O
O

19.1. Draw the structures of intermediate 1, by product 2 and the protein 3, and clearly identify the stereochemistry.
19-2 Some cyclopeptide can also undergo intramolecular rearrangement via the same mechanism to give a new
cyclopeptide. Draw the structure of compound 4, and clearly identify the stereochemistry.

HN
HS

4
19-3 The ester of salicylaldehyde can reacts with a peptide containing a cysteine residue at the N terminal to form a new
amide bond. Draw the structures of intermediate 5 and by product 6 and clearly identify the stereochemistry.
19-4 The reaction of organic azides with trivalent phosphorous compounds to afford the corresponding azaylides is known as
the Staudinger reaction. In certain cases Staudinger reactions were used to facilitate the formation of amide bonds. As shown
below, the aza ylide intermediate 7 will form a bridged intermediate 8 and then give the amide product through hydrolysis.
Draw the structures of intermediate 7 and 8.

Peptide Staudinger Ligation

19-5 Linear peptides containing cysteine and lysine can react with ortho-phthalaldehydes to give cyclopeptides with an
isoindole linker
19-6 Besides cysteine, methionine can be selectively labeled with oxaziridine-based reagents under biocompatible reaction
conditions. As shown below, the reaction can undergo two different pathways. Draw the structures of compounds 10, 11, 12.
 Problema 21

21-1 The first total synthesis of ()-Schindilactone A began with the construction of B/C ring system. Thus, the key
intermediate 8 was synthesized from 1 and 2 in 7 steps as shown below.

21-1-1 Draw the structures of compounds 1 and 4 and clearly identify the stereochemistry where necessary.
21-1-2 Draw two anion intermediates in the transformation from 3 to 4.
21-1-2 Draw the structure of compound 6.
MeOOC

O
1
21-2 Treatment of 8 with but-3-enyl magnesium bromide stereoselectively afforded 9, which was oxidized to 10. Draw the
structure of 9, including the appropriate stereochemistry.
21-3 Reaction of alcohol 10 with benzyl2,2,2-trichloroacetimidateunder the catalysis of trifluoromethanesulfonic acid
(TfOH) afforded 11. Treating 11 with vinyl magnesium bromide resulted in 12, a key intermediate for the total synthesis of
()-Schindilactone A.

21-3-1 Benzyl2,2,2-trichloroacetimidate as a weak base can be protonated by an acid like TfOH, leading to activation of C-O
bond of benzyloxy group. Draw the main resonance structures of conjugate acid of benzyl 2,2,2-trichloroacetimidate.
21-3-2 Draw the structure of 11, including the appropriate stereochemistry
21-3-3 Chose the correct statement indicating the reaction of 10 with benzyl2,2,2-trichloro-acetimidate.
(a) E2 reaction (b) SN1 reaction
(c) SN2 reaction (d) Nucleophilic addition
21-3-4 Draw the structure of the by-product formed in the conversion of 10 into 11. Hint: this by-product contains three
chlorine atoms.
Reactia de esterificare cu tricloroacetamidat