Samarium diiodide-induced cyclizations

98 Pages·1991·3.5 MB·English

by  Trivellas, Antigone, 1960-

SAMARIUMDIIODIDE-INDUCEDCYCLIZATIONS
BY
ANTIGONETRIVELLAS
ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL
OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT
OFTHEREQUIREMENTS FORTHEDEGREEOF
DOCTOROFPHILOSOPHY
UNIVERSITYOFFLORIDA
1991
Copyright© 1991
by
AntigoneTrivellas

ACKNOWLEDGEMENTS
Thisistheendofalong road. I would liketo take this opportunity
tothankallthosewhohelpedandassistedmeduringtheseyears.
Iamgrateful to Mikefor helping me start school, and to Phuoc and
his family for giving me a family here, ever so far away from home.
Thankstomyfirstteacher in chemistry, Dr. Nielsen, for opening theroad
tochemistryforme. SpecialthankstoDr. Deyrupforeasing the transition
from Santa Fe to UF and for all his constant caring and wise advice
throughthedifficulttimes. ManythankstoDr. Battiste, DrJones and Dr.
Enholmfor their teachings. I owe appreciation to Dr. Enholmfor his cri-
tiqueineachchapterandhishelpfulguidancethroughtheyears.
Finally, I would like to thank all who shared laughter with me and
heldmyhandduringdifficulttimes.
tv
TABLEOFCONTENTS
Page
ACKNOWLEDGEMENTS iv
LISTOFFIGURES vi
ABSTRACT vii
CHAPTERS
INTRODUCTION
1 1
2 SIMPLECASES 8
Aldehyde-AlkeneCouplings 9
Ketone-AlkeneCouplings 13
MechanisticConsiderations 14
3 CARBOCYCLES FROMCARBOHYDRATES 20
4 SEQUENTIALRADICALCYCLIZATION-
CARBONYLADDITION 36
5 EXPERIMENTAL 47
General 47
Procedures andResults 48
6 SUMMARY 82
LISTOFREFERENCES 85
BIOGRAPHICALSKETCH 88
v
LISTOFFIGURES
1-
Page
2-
FIGURES
3-
1 SomefundamentalreactionsofSml2 2
3-
1 Alcoholateanion 16
4-
1 Arabinosecyclicether 24
3-2 Crystalx-raystructureforcarbocycle80 29
3 Crystalx-raystructureforcarbocycle90 33
1 Crystalx-raystructureforcarbocycle96 38
4-2 Crystalx-raystructureforcarbocycle 101 43
vi
AbstractofDissertationPresentedtotheGraduateSchool
oftheUniversityofFloridainPartialFulfillmentofthe
RequirementsfortheDegreeofDoctorofPhilosophy
SAMARIUMDIIODIDE-INDUCEDCYCLIZATIONS
By
AntigoneTrivellas
August, 1991
Chairman: EricJ. Enholm
MajorDepartment: Chemistry
Thedistinctiveproficiencyofsamariumdiiodidereagentin mediating
ketones/aldehydes-olefin reductive cyclizations was investigated. Ketones
and aldehydes tethered to electron deficient olefins were studied for the
formationofcarbocycles. In a singleprocess, up to four new stereogenic
centersweregeneratedwithsurprisingstereocontrol.
At the first stage, Sml2 was used for the intramolecular reductive
cyclization ofketones and aldehydes tethered to electron deficient olefins
for theformation ofsimple five-membered carbocycles. The goal was to
lookattheolefinelectroniceffectsinthereaction and thepossible correla-
tion of the olefin geometry in the starting substrate with regards to the
product stereochemistry. With aldehyde starting materials, the (E)-ge-
ometric isomer gave a ratio only slightly favoring the anti-disposed pro-
duct. In contrast, when cyclicketones were used, a strong dependenceof
theproductdiastereoselectivity on the olefin geometry was observed. In
onecase, the(E)-geometric isomerproduced the antiproductnearly exclu-
sively, while the (Z)-geometric isomer led to an equal anti:syn mixture of
products.
vii
This chemistry was next adapted to more complex unsaturated sys-
tems suchascarbohydrates, whichprovedtobeanexcellentmethodforthe
stereoselectivepreparation ofpolyhydroxylated carbocycles. These exper-
iments demonstrated a strong correlation in the diastereoselectivity of the
productsdependingonwhethertheolefingeometryofthe starting carbohy-
drate was E or Z. In all cases examined, the (Z)-olefin in the starting
carbohydrate template favored the syn isomer and the (E)-olefin geometry
favoredtheantiisomer.
In the lastvariation ofthis process, theproton donor in the key re-
action was substituted for carbonyl electrophiles such as aldehydes and
ketones. Allsugartemplates, upontreatmentwithSml2, underwent an ini-
tial radical olefin cyclization. Subsequently, reduction oftheintermediate
radical generated through this process produced a transient organosama-
riumenolate that was trapped in situ by aldehydes and ketones to produce
carbocycles withtwonewcarbon-carbonbonds.
In conclusion, these studies represent the first applications of the
Sml2 reagent to carbohydrates. Through these transformations the Sml2
reductiveprocedureprovedtohaveunleashedexcitingnew possibilities for
stereoselectiveorganicprocesses.
vm
CHAPTER
1
INTRODUCTION
Lanthanides, alsoknownasrareearths, were discovered and charac-
terized from the 18th century up until the middle of the 20th century.1
Theyareelementsthatpossess apartiallyfilled4felectronicsubshell and a
xenoncore. Theirmainoxidationstate is +3, therefore Ln(IV) compounds
are powerful oxidants.2'4 The dipositive Ln(II) state is unusual for lan-
thanides andtheonlyones thatcan attain iteasily areeuropium, samarium
andytterbium. IntheLn(II) state, the driving force forreactions is a sin-
gleelectrontransfertogiveLn(III) species. Therefore, their use as reduc-
ingagentshasprovenveryusefulinorganic synthesis.5 They also exhibit
rich coordination chemistry and high oxophilicity. Samarium (II) has the
highest known reduction potential (Sm+3/Sm2+ = -1.55 V) for species
easily soluble in organicmedia, and its strong affinity foroxygen is very
significant since it can be helpful in the Lewis acid activation of oxy-
genatedorganicfunctions.6
In 1977, seminalworkbyNamyandKagan7 showedthat Sml2 could
beobtainedbyreactingsamariumpowderand 1,2 diiodoethane in THF and
introducedit as areagent useful for the formation ofcarbon-carbon bonds
andthetransformationofvarioustypesoffunctionalities.
Kagan8 has subsequently reported a summary of these transforma-
tionswhicharelistedinScheme 1-1 (reactions [1] to [13]). Thus, ketones
andaldehydesin thepresence ofprotic solvents arereduced to the corres-
pondingalcohols (reactions [1] and[2]). Intheabsenceofprotondonors
1
C R ]
2
O
R-Cii-H + 2 Sml2 MTeHOFH RCH2OH [ 1 ]
O
R-Cii-R + 2 Sml2 MTeHOFH WRCHOHR [ 2
O
R-Cii-H + 2 Sml2 THF RCHOH-CHOHR 3]
O
R-Cii-R + 2 Sml2 THF HO OH [ 4]
R-X + Sml THF R-H 5
2 [ l
PhCH2X + Sml2 THF PhCH2CH2Ph 6 1
O
R—Sii-R + 2 Sml2 21))THH30F+ R—S-R
Ph(CH)2C02R + 2 Sml2 21))THH30F+ Ph(CH2)2C02R [:«]
+ Sml THF RCH=CHR >]
2
O —OH
R1—C-R2 + R3X 2Sml2 R1 h~R2 10
THF , 1
R3
O OK
R1— -R2 + XCCH^CO^t 2TSHmlF2 R1—|— 2 |.»]
O O(C0H2)nC02Et
2R-Cii-Cl + 2 Sml2 THF R-Cii-Cn-R l>i
O O 0 OH
R1—C-Cl + R3—C-R2 2TSHmlF2 R1—CII —C1-R2 r>3]
R3
Figure 1-1
SomefundamentalreactionsofSml2