Oxidation of 2,2,3,3-Tetramethyl-1,4-diphenyl-5,6-dithiabicyclo[2.1.1]hexane and Its Oxidation Products: An Important Role of 1,3-Transannular Interaction in the 1,3-Dithietane Part
Abstract:Oxidation of 2,2,3,3-tetramethyl-1,4-diphenyl-5,6-dithiabicyclo[2.1.1]hexane with m-chloroperbenzoic acid gives two isomeric endo- (4a) and exo-sulfoxides (4b), three S,S′-dioxides (endo, exo-5a, exo, exo-5b, and endo, endo-5c), and an S,S,S′-trioxide (6). The relative reactivity to further oxidation is 4b >> 4a and 5b > 5a, which suggests that the attractive 1,3-transannular interaction operative in 1,3-dithietane part of 4a and 5a decreases the reactivity of 4a and 5a. 4b isomerizes to 4… Show more
“…Intermolecular cycloadducts of thiones and thione S -oxides are known 13c20a yielding 1b over the sterically now more difficult 1,3-dipolar cycloaddition (Scheme ). The formation of 14a , b from ( Z )- 21a but not from ( E )- 21a is analogous to the observation that syn -carbonyl oxide 22a cyclizes to give 1-phenyl-2,3,7-oxabicyclo[2.2.1]heptane ( 23 ; eq 2) (bridghead CH, δ 6.22 ppm) whereas anti -carbonyl oxide 22b , because it cannot achieve a suitable conformation for intramolecular cyclization, gives mainly oligomeric material (eq 3) 20b…”
Section: Resultsmentioning
confidence: 54%
“…Upon analogous oxidation of ( Z , Z )- 2 , steric effects associated with the Z double bonds lead the intermediate to adopt a transition state geometry in which the thiosulfinate oxygen is pseudoequatorial, resulting in the formation of ( E )-(2 R ,3 S /2 S ,3 R )-2,3-dimethyl-1,4-butanedithial S -oxide (( E )- 21a ), where the geometry of the ( E )-CS + O - group favors the intramolecular head-to-tail [2 + 2] process,20a yielding 1b over the sterically now more difficult 1,3-dipolar cycloaddition (Scheme ). The formation of 14a , b from ( Z )- 21a but not from ( E )- 21a is analogous to the observation that syn -carbonyl oxide 22a cyclizes to give 1-phenyl-2,3,7-oxabicyclo[2.2.1]heptane ( 23 ; eq 2) (bridghead CH, δ 6.22 ppm) whereas anti -carbonyl oxide 22b , because it cannot achieve a suitable conformation for intramolecular cyclization, gives mainly oligomeric material (eq 3) 20b 3 4 5 6 …”
Reduction (LiAlH4) of propyl 1-propynyl sulfide
(8) to (E)-1-propenyl propyl sulfide
((E)-10), C−S cleavage
(Li/NH3) to lithium (E)-1-propenethiolate (Li
(E)-11), and reaction with
MeSO2Cl gives
(E,E)-bis(1-propenyl) disulfide
((E,E)-2);
i-Bu2AlH reduction of 8 to
(Z)-10 and reaction with Li/NH3 and
then MeSO2Cl gives
(Z,Z)-2 via Li
(Z)-11. Reaction of MeSO2SR
(R = Me (12a), n-Pr (12b),
CH2CHCH2 (12c), CHCHMe
(12d)) with K (E)-11
gives (E,Z)-2 from
(Z)-12d; Li
(E,Z)-11 gives alkyl (E)-
and (Z)-1-propenyl disulfides (MeCHCHSSR, R =
Me
(3a), n-Pr (3b),
CH2CHCH2 (3c)) from
12a−c, respectively. Oxidation at −60
°C of (E,E)-, (Z,Z)-, and
(E,Z)-2
gives (E)-1-propenesulfinothioic acid
S-(E)-1-propenyl ester
((E,E)-13,
(E,E)-MeCHCHS(O)SCHCHMe)
from
(E,E)-2,
(Z,Z)-13 from
(Z,Z)-2, and ca. 2:1
(E,Z)-13)/(Z,E)-13
from (E,Z)-2. Warming
(Z,Z)-13 gives (±)-(1α,2α,3β,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane
5-oxide (1a),
endo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14a), and
exo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14b).
Warming (E,E)-13 gives
14a and 14b;
(E,Z)-13/(Z,E)-13
gives
(1α,2α,3α,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide (1b),
exo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14c), and endo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14d). Oxidation of 3a−c gives
MeCHCHSS(O)R
(4) and MeCHCHS(O)SR (5). At
−60 °C, m-CPBA (2 equiv) converts
(E,E)-2 into
(Z,Z)-d,l-2,3-dimethyl-1,4-butanedithial 1,4-dioxide (26) while
(Z,Z)-2 gives meso- and
d,l-26. With NaIO4,
4/5 (R = Me) gives (E)- or
(Z)-12a and MeCHCHSO2SMe (6a);
with m-CPBA
(Z)-MeS(O)CHMeCHS+O-
(25a) forms. At 85 °C 2 gives
1:1 cis- and
trans-2-mercapto-3,4-dimethyl-2,3-dihydrothiophene
(29).
“…Intermolecular cycloadducts of thiones and thione S -oxides are known 13c20a yielding 1b over the sterically now more difficult 1,3-dipolar cycloaddition (Scheme ). The formation of 14a , b from ( Z )- 21a but not from ( E )- 21a is analogous to the observation that syn -carbonyl oxide 22a cyclizes to give 1-phenyl-2,3,7-oxabicyclo[2.2.1]heptane ( 23 ; eq 2) (bridghead CH, δ 6.22 ppm) whereas anti -carbonyl oxide 22b , because it cannot achieve a suitable conformation for intramolecular cyclization, gives mainly oligomeric material (eq 3) 20b…”
Section: Resultsmentioning
confidence: 54%
“…Upon analogous oxidation of ( Z , Z )- 2 , steric effects associated with the Z double bonds lead the intermediate to adopt a transition state geometry in which the thiosulfinate oxygen is pseudoequatorial, resulting in the formation of ( E )-(2 R ,3 S /2 S ,3 R )-2,3-dimethyl-1,4-butanedithial S -oxide (( E )- 21a ), where the geometry of the ( E )-CS + O - group favors the intramolecular head-to-tail [2 + 2] process,20a yielding 1b over the sterically now more difficult 1,3-dipolar cycloaddition (Scheme ). The formation of 14a , b from ( Z )- 21a but not from ( E )- 21a is analogous to the observation that syn -carbonyl oxide 22a cyclizes to give 1-phenyl-2,3,7-oxabicyclo[2.2.1]heptane ( 23 ; eq 2) (bridghead CH, δ 6.22 ppm) whereas anti -carbonyl oxide 22b , because it cannot achieve a suitable conformation for intramolecular cyclization, gives mainly oligomeric material (eq 3) 20b 3 4 5 6 …”
Reduction (LiAlH4) of propyl 1-propynyl sulfide
(8) to (E)-1-propenyl propyl sulfide
((E)-10), C−S cleavage
(Li/NH3) to lithium (E)-1-propenethiolate (Li
(E)-11), and reaction with
MeSO2Cl gives
(E,E)-bis(1-propenyl) disulfide
((E,E)-2);
i-Bu2AlH reduction of 8 to
(Z)-10 and reaction with Li/NH3 and
then MeSO2Cl gives
(Z,Z)-2 via Li
(Z)-11. Reaction of MeSO2SR
(R = Me (12a), n-Pr (12b),
CH2CHCH2 (12c), CHCHMe
(12d)) with K (E)-11
gives (E,Z)-2 from
(Z)-12d; Li
(E,Z)-11 gives alkyl (E)-
and (Z)-1-propenyl disulfides (MeCHCHSSR, R =
Me
(3a), n-Pr (3b),
CH2CHCH2 (3c)) from
12a−c, respectively. Oxidation at −60
°C of (E,E)-, (Z,Z)-, and
(E,Z)-2
gives (E)-1-propenesulfinothioic acid
S-(E)-1-propenyl ester
((E,E)-13,
(E,E)-MeCHCHS(O)SCHCHMe)
from
(E,E)-2,
(Z,Z)-13 from
(Z,Z)-2, and ca. 2:1
(E,Z)-13)/(Z,E)-13
from (E,Z)-2. Warming
(Z,Z)-13 gives (±)-(1α,2α,3β,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane
5-oxide (1a),
endo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14a), and
exo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14b).
Warming (E,E)-13 gives
14a and 14b;
(E,Z)-13/(Z,E)-13
gives
(1α,2α,3α,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide (1b),
exo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14c), and endo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane
(14d). Oxidation of 3a−c gives
MeCHCHSS(O)R
(4) and MeCHCHS(O)SR (5). At
−60 °C, m-CPBA (2 equiv) converts
(E,E)-2 into
(Z,Z)-d,l-2,3-dimethyl-1,4-butanedithial 1,4-dioxide (26) while
(Z,Z)-2 gives meso- and
d,l-26. With NaIO4,
4/5 (R = Me) gives (E)- or
(Z)-12a and MeCHCHSO2SMe (6a);
with m-CPBA
(Z)-MeS(O)CHMeCHS+O-
(25a) forms. At 85 °C 2 gives
1:1 cis- and
trans-2-mercapto-3,4-dimethyl-2,3-dihydrothiophene
(29).
“…These spectral data indicate the symmetrical structure of 13 . The configuration of the sulfoxide groups is determined to be endo , endo and not exo , exo , with respect to the six-membered ring, on analyzing the 1 H NMR spectrum by taking the anisotropic effect of the sulfoxide groups into account . The endo -sulfoxide structure of 14 , determined by X-ray crystallography, also supports the above assignment on 13 .…”
Section: Resultsmentioning
confidence: 60%
“…The residue was subjected to column chromatography (CH 2Cl2) to give the endo,exodioxide 15 (150 mg, 80%) along with small amounts of the dicarbonyl compound 12, the disulfine 16, and the monothiodiketone 17. CH2Cl2, c ) 1.00 × 10 -2 M, nm) λmax ( ) 537 (10); MS m/z (rel intensity) 284 (M + , 5), 57 (100); HRMS calcd for [C17H32OS] + 284.2174, found 284.2197.…”
Two sterically congested cycloalkenes (9 and 10), congeners of tetra-tert-butylethylene, were synthesized and characterized. Oxidation of the bicyclic 1,3-dithietane 8 with dimethyldioxirane (DMD) gave the endo,endo-disulfoxide 13, thermal isomerization of which to the endo,exo-disulfoxide 15 followed by oxidation with DMD gave the trioxide 18. Heating 18 in refluxing 1,3-dimethyl-2-imidazolidinone furnished 1,2-di-tert-butyl-3,3,5,5-tetramethylcyclopentene (9) in 69% yield by a 2-fold extrusion process. The reaction of the 1,6-diketone dihydrazone 23 with Se(2)Cl(2) gave the selenadiazoline 34 and the 1,3-diselenetane 35. Heating 34 at 115-130 degrees C gave 1,2-di-tert-butyl-3,3,6,6-tetramethylcyclohexene (10), a "didehydro" derivative of tetra-tert-butylethylene, in 43% yield. The C=C bond in 10 is strained in degree comparable to those of most strained alkenes reported so far.
Extrusion reactions may be defined as chemical reactions in which an atom or small molecular fragment Y connected to two other atoms W and Z is lost from a molecule, leading to a product in which W becomes directly bonded to Z. Cheletropic reactions that afford aromatic or conjugated π systems by loss of a stable atomic or molecular fragment have also been classified as extrusion reactions. Typically, the fragments liberated in these reactions are small, stable inorganic molecules or atoms such as carbon monoxide, carbon dioxide, sulfur, sulfur monoxide, sulfur dioxide, selenium, tellurium, oxygen and nitrogen. This chapter primarily deals with the synthesis of arenes, heterocycles, 1,3‐dienes and polyenes using such extrusion processes. The utility of these reactions in the synthesis of sterically hindered molecules, dendrimers, pheromones, and other natural products are highlighted. The use of extrusion reactions for the “Click and Release” approach in drug development is also introduced.
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