10.1021/ja9716160.s001
Hirokazu Urabe
Hirokazu
Urabe
Ken Suzuki
Ken
Suzuki
Fumie Sato
Fumie
Sato
Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters
Mediated by (η<sup>2</sup>-Propene)Ti(O-<i>i</i>-Pr)<sub>2</sub>. Facile Construction of
Mono- and Bicyclic Skeletons with Stereoselective Introduction
of a Side Chain. A Synthesis of <i>d</i>-Sabinene
American Chemical Society
1997
trimethylsilyl
1.1 equiv
allylic
bond
substituent
yield
tert
Pr
BuOH
titanabicycle 7
ethyl
ethoxycarbonyl
D 2 O
incorporation
PrOD
hydrolysis
ketone
Et 2 CO
monodeuterated product 10
Ti
cyclization
stereochemistry
electrophile
deuterium
butyl
bicyclic skeleton
octen
1997-10-22 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Intramolecular_Cyclization_of_2_7-_or_2_8-Bis-unsaturated_Esters_Mediated_by_sup_2_sup_-Propene_Ti_O-_i_i_i_-Pr_sub_2_sub_Facile_Construction_of_Mono-_and_Bicyclic_Skeletons_with_Stereoselective_Introduction_of_a_Side_Chain_A_Synthesis_of_i_d_i_-Sabinene/3666156
<i>tert</i>-Butyl 2-en-7-ynoate <b>6</b> was
treated with
(η<sup>2</sup>-propene)Ti(O-<i>i</i>-Pr)<sub>2</sub>
(<b>3</b>), generated <i>in</i> <i>situ</i> from
Ti(O-<i>i</i>-Pr)<sub>4</sub> or Ti(O-<i>i</i>-Pr)<sub>3</sub>Cl and
<i>i</i>-PrMgCl, in ether at −50 to −20 °C to afford the
product <b>8</b> in good yield. The presence
of the intermediate titanabicycle <b>7</b> was verified by
bis-deuterolysis with excess D<sub>2</sub>O. When the
titanabicycle <b>7</b> was
treated with 1.1 equiv of <i>i</i>-PrOD and then worked up as
usual, the monodeuterated product <b>10</b> was obtained
with
high site selectivity and stereoselectivity. Other electrophiles
such as aldehydes and ketones also reacted with the
titanabicycle in a highly stereoselective manner to give cyclopentanes
having a stereo-defined side chain. On the
contrary, treatment of the corresponding ethyl ester, ethyl
8-(trimethylsilyl)-(<i>E</i>)-2-octen-7-ynoate (<b>28</b>),
with <b>3</b> under
the same conditions followed by the addition of 1.1 equiv of
<i>s</i>-BuOH afforded
2-(trimethylsilyl)-1-bicyclo[3.3.0]octen-3-one (<b>32</b>) in 80% yield. Quenching the same
reaction mixture with <i>i</i>-PrOD, EtCHO, and
Et<sub>2</sub>CO in place of
<i>s</i>-BuOH gave 4-deuterio (with exclusive deuterium
incorporation), 4-(1-hydroxypropyl), and
4-(1-ethyl-1-hydroxypropyl) derivatives of the above bicyclic ketone (<b>34</b>,
<b>35</b>, and <b>36</b>) in good yields. These
electrophiles were always
introduced from the convex face of the bicyclic skeleton. The
stereochemistry of the cyclization could be controlled
by an allylic substituent such as
(<i>tert</i>-butyl)dimethylsiloxy or butyl group to a high
degree yet with a reversal
diastereoselection to give <b>45</b> or <b>47</b>. The
reaction of ethyl 7-octen-2-ynoate (<b>56</b>) and <b>3</b> at
−50 to 0 °C took place in
a quite different way to afford
1-[(ethoxycarbonyl)methyl]bicyclo[3.1.0]hexane
(<b>64</b>) in 74% yield after hydrolysis.
If the simple hydrolysis is replaced by deuterolysis or the action
of diethyl ketone,
1-[(ethoxycarbonyl)dideuteriomethyl]
(with 99% deuterium incorporation), or
1-[(ethoxycarbonyl)(3-pentylidene)methyl] derivative of the
above product
(<b>65</b> or <b>66</b>) was obtained in good yields. A
7-en-2-ynoate having an internal <i>Z</i>-double bond such as
<b>80</b> afforded a
single stereoisomer <b>82</b> with the substituent at the
<i>endo</i> position of the bicyclic skeleton, suggesting that
the
stereochemical integrity of the <i>Z</i>-double bond of the
starting material was retained in the product. An alkyl
substituent
at the allylic position of the substrates like <b>74</b> and
<b>76</b> nicely controlled the stereochemistry of the cyclization
to
afford single products <b>75</b> and <b>77</b> with the
substituent being placed in the <i>exo</i> orientation of the
bicyclic structure.
This high diastereoselectivity was successfully applied to an
enantioselective synthesis of <i>d</i>-sabinene from an
optically
active enynoate via nearly complete chirality transfer.