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Chiral diphosphine ligands and new reactions of organozinc compounds [Elektronische Ressource] / von Andrey Gavryushin

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Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München Chiral Diphosphine Ligands and New Reactions of Organozinc Compounds von Andrey Gavryushin aus Ruzaewka, Russland München 2006 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 von Herrn Prof. Dr. Paul Knochel betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig, und ohne unerlaubte Hilfe erarbeitet. München, am 09. 01. 2007. Andrey Gavryushin Dissertation eingereicht am 11. 01. 2007 1. Gutachter: Prof. Dr. Paul Knochel 2. Gutachter: Prof. Dr. Hans Rudolf Pfaendler Mündliche Prüfung am 09. 02. 2007 2 This work was carried out from August 2001 to July 2006 under the guidance of Prof. Knochel at the Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität, Munich. I would like to thank Prof. Dr. Paul Knochel for giving me the opportunity of doing my Ph.D. in his group, for his invaluable support through this time. I am also very grateful to Prof. Dr. H. R. Pfaendler for agreeing to be my “Zweitgutachter”, as well as Prof. Dr. K. Karaghiosoff, Prof. Dr. T. Lindel, Prof. Dr. H. Zipse and Dr. L. Ackermann for the interest shown in this manuscript by accepting to be referees. I thank Dr. Darunee Soorukram, Tobias Thaler and Dr.

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Published 01 January 2006
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Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München






Chiral Diphosphine Ligands and New Reactions of
Organozinc Compounds





von

Andrey Gavryushin



aus

Ruzaewka, Russland





München 2006
Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Herrn Prof. Dr. Paul Knochel betreut.




Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, und ohne unerlaubte Hilfe erarbeitet.


München, am 09. 01. 2007.








Andrey Gavryushin




Dissertation eingereicht am 11. 01. 2007

1. Gutachter: Prof. Dr. Paul Knochel

2. Gutachter: Prof. Dr. Hans Rudolf Pfaendler

Mündliche Prüfung am 09. 02. 2007
2 This work was carried out from August 2001 to July 2006 under the guidance of Prof.
Knochel at the Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität,
Munich.


I would like to thank Prof. Dr. Paul Knochel for giving me the opportunity of doing my Ph.D.
in his group, for his invaluable support through this time.

I am also very grateful to Prof. Dr. H. R. Pfaendler for agreeing to be my “Zweitgutachter”, as
well as Prof. Dr. K. Karaghiosoff, Prof. Dr. T. Lindel, Prof. Dr. H. Zipse and Dr. L.
Ackermann for the interest shown in this manuscript by accepting to be referees.

I thank Dr. Darunee Soorukram, Tobias Thaler and Dr. Vicente del Amo for the careful
correction of this manuscript.

I would like to thank the Ludwig-Maximilians-Universität and Saltigo GmbH for the financial
support.

My special thanks to Vladimir Malakhov for his immense and patient help in everyday life as
well as in scientific work.

My thanks to all the students, diplomants and postdocs that came and went during this time
for their friendship that made these years such an enjoyable experience. I would like to thank
my labmates Katja Tappe, Tanasri Bunlaksananusorn, Viet-Anh Vu, Ching-Yuan Liu, Georg
Manolikakes, Vicente del Amo and all others for the excellent time and friendly atmosphere
during the working hours.

I would also like to thank Beatrix Cammelade, Yulia Tsvik and Simon Matthe for their help in
organizing everyday life in the lab, as well as the analytical team, Dr. D. Stephenson, Dr. C.
Dubler, B. Tschuk, and P. Maier for their help.

I would like to thank my family, my wife and my parents for their love and great support, as
well as all my friends for their kindness through these years.

Thank you very much!



3 Parts of this Ph. D. thesis have been published:

1. Gavryushin, Andrei; Polborn, Kurt; Knochel, Paul. „Novel chiral diphosphine ligands with a
pinene core obtained via an allylphosphinite-allylphosphine oxide rearrangement”. Tetrahedron:
Asymmetry 2004, 15, 2279-2288.
2. Gavryushin, Andrei; Kofink, Christiane; Manolikakes, Georg; Knochel, Paul. “Efficient Cross-
Coupling of Functionalized Arylzinc Halides Catalyzed by a Nickel Chloride-Diethyl Phosphite
System.” Organic Letters 2005, 7, 4871-4874.
3. Krasovskiy, Arkady; Gavryushin, Andrey; Knochel, Paul. “A general thiolation of magnesium
organometallics using tetramethylthiuram disulfide.” Synlett 2005, 2691-2693.
4. Krasovskiy, Arkady; Malakhov, Vladimir; Gavryushin, Andrei; Knochel, Paul. „Efficient
synthesis of functionalized organozinc compounds by the direct insertion of zinc into organic iodides
and bromides.” Angewandte Chemie, International Edition 2006, 45, 6040-6044.
5. Krasovskiy, Arkady; Gavryushin, Andrey; Knochel, Paul. “Highly stereoselective access to sulfur
derivatives starting from zinc organometallics.“ Synlett 2006, 792-794.
6. Gavryushin, Andrei; Kofink, Christiane; Manolikakes, Georg; Knochel, Paul. “An efficient
Negishi cross-coupling reaction catalyzed by nickel(II) and diethyl phosphite.” Tetrahedron 2006,
62, 7521-7533.
Patents:
1. Knochel, Paul; Bunlaksananusorn, Tanasari; Gavryushin, Andrei. “Chiral diphosphinoterpenes and
transition metal complexes thereof.” U.S. Pat. Appl. Publ. (2005), US 2005267316.
2. Knochel, Paul; Bunlaksananusorn, Tanasari; Gavryushin, Andrei. “Chiral diphosphines with cyclic
diterpene backbone as ligands for transition metal-catalyzed asymmetric hydrogenation, addition and
substitution reactions and process for preparation thereof.” Eur. Pat. Appl. (2005), EP 1595886 .
3. Knochel, Paul; Bunlaksananusorn, Tanasari; Gavryushin, Andrei. “An improved process for
preparation of chiral diphosphines with cyclopentane backbone as ligands for asymmetric transition
metal-catalyzed hydroboration, hydrogenation and allylic substitution.” Eur. Pat. Appl. (2005), EP
1595885.
4. Knochel, Paul; Gavryushin, Andrey; Kofink, Christiane C. “An iron- , nickel- and cobalt-catalyzed
cross-coupling reactions of organozinc compounds.” Patent pending.
5. Knochel, Paul; Gavryushin, Andrey; Malakhov, Vladimir; Krasovskiy, Arkady. “New preparation
of organometallic compounds in the presence of lithium salts.” Patent pending.





4












To Victoria, with love.

















5








And I gave my heart to seek and search out by wisdom
concerning all things that are done under heaven: this
sore travail hath God given to the sons of man to be
exercised therewith.
Ecclesiastes, 1:13















6 ABBREVIATIONS

Ac acetyl
AcOH acetic acid
Ar aryl
Bn benzyl
Boc tert-butoxycarbonyl
br. broad
calcd. calculated
CH Cl dichloromethane 2 2
Cy cyclohexyl
d double
dba trans,trans-dibenzylideneacetone
dec. decomposition
DMAP 4-dimethylaminopyridine
DME 1,2-dimethoxyethane
DMF N,N-dimethylformamide
DMSO dimethyl sulfoxide
equiv. equivalent
EI electron-impact
Et ethyl
FAB fast-atom bombardment
FG functional group
GC gas chromatography
h hour
HMPT hexamethylphosphorous triamide
HRMS high resolution mass spectroscopy
n-Bu n-butyl
i-Pr isopropyl
IR infra-red
J coupling constant (NMR)
LG leaving group
M molarity
m meta
m multiplet
7 Me methyl
Met metal
min minute
mol. mole
mp. melting point
MS mass spectroscopy
NBS N-bromosuccinimide
NMR nuclear magnetic resonance
Nu nucleophile
o ortho
p para
Pent pentyl
PG protecting group
Ph phenyl
Piv pivaloyl
q quartet
rt room temperature
s singlet
t triplet
t-Bu tert-butyl
TBS tert-butyldimethylsilyl
TES triethylsilyl
Tf triflate
TFA trifluoroacetic acid
tfp tri-(2-furyl)phosphine
THF tetrahydrofuran
TLC thin layer chromatography
TMEDA N,N,N',N'-tetramethylethylenediamine
TMS trimethylsilyl
TMP 2,2,6,6-tetramethylpiperidyl
TP typical procedure
Ts 4-toluenesulfonyl


8
Table of contents

Theoretical Part
Part I. -------------------------------------------------------------------------------------------------------------------------- 13
Synthesis of chiral diphosphine ligands --------------------------------------------------------------------------------- 13
1. Overview and objectives ------------------------------------------------------------------------------------------------ 13
1.1 General overview ---------------------------------------------------------------------------------------------------- 13
1.2. Objectives ------------------------------------------------------------------------------------------------------------- 14
2. Allylphosphinite-allylphosphine oxide [2,3]-sigmatropic rearrangement on exocyclic systems and its
application to the synthesis of new phosphorus ligands for asymmetric catalysis. ----------------------------- 15
2.1 Chiral diphosphines with a saturated cyclic core and their applications in asymmetric catalysis. -------- 15
2.2 [2,3]-sigmatropic rearrangement as a method for preparation of novel phosphine ligands--------------- 19
2.2.1. Preliminary studies of [2,3]-sigmatropic rearrangement on exocyclic systems ------------------------- 22
2.2.2. Studies on the allylic double bond functionalization in allylphosphine oxides-------------------------- 24
2.3 Preparation of optically pure diphosphine ligands with a cyclopentane core ------------------------------- 29
2.3.1. Enzymatic resolution of 2-alkylidenecyclopentanols -------------------------------------------------------- 30
2.3.2. Enantioselective synthesis of alkyl-substituted analogs of PCPP------------------------------------------ 34
2.4 Synthesis of new chiral diphosphines with a natural terpene framework ------------------------------------- 37
2.4.1. Preparation of diphosphine ligands starting from (-)-myrtenol--------------------------------------------- 38
2.4.2. Preparation of diphosphine ligands from trans-pinocarveol (47) ------------------------------------------ 41
3. Novel approaches to the synthesis of chiral diphosphine ligands with a cyclopentane scaffold. ---------- 47
3.1 Enzymatic kinetic resolution for the preparation of optically pure 2-substituted cyclopentanols. --------- 47
3.2 Modular enantioselective synthesis of PCPP ligand ------------------------------------------------------------- 51
3.3 Enantioselective synthesis of a new 1,4-diphosphine ligand with a cyclopentane scaffold ----------------- 58
4. Applications of the new ligands in the transition metal-catalyzed asymmetric reactions. ----------------- 64
4.1. Rh-catalyzed asymmetric hydrogenation of acetamidocinnamates and acetamidoacrylates.-------------- 64
4.2. Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate. ----------------------------------------------- 69
4.3 Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to cyclohexenone. ---------------------------- 71
4.4. Rh-catalyzed asymmetric hydroboration of styrene.------------------------------------------------------------- 74
4.5 Rh- and Ru-catalyzed asymmetric hydrogenation of C=N and C=O bonds and Pd-catalyzed allylic
substitution reactions. ---------------------------------------------------------------------------------------------------- 75
Part II. ------------------------------------------------------------------------------------------------------------------------- 78
New reactions of organozinc compounds ------------------------------------------------------------------------------- 78
5. New cross-coupling reaction of triorganosilylzinc compounds with aryl triflates. -------------------------- 79
6.1 Reaction optimization ------------------------------------------------------------------------------------------------ 81
6.2 Cross-coupling reaction of silylzinc and silylaluminium compounds------------------------------------------ 84
6.3 Conversion of phenols into aryl iodides and arylboronic esters. ----------------------------------------------- 90
6. Novel method of thiolation of organozinc and organomagnesium compounds.------------------------------ 94
9 6.1 New thiolation reaction of organomagnesium compounds. ----------------------------------------------------- 94
6.2 New thiolation reaction of organozinc compounds--------------------------------------------------------------- 97
6.3 Synthesis of thiols and sulfides from dithiocarbamates ---------------------------------------------------------- 99
7. New efficient Ni-catalyzed cross-coupling of arylzinc compounds--------------------------------------------- 100
7.1. Optimization of the reaction conditions and the catalytic system.-------------------------------------------- 102
7.2 Ni-catalyzed cross-coupling of arylzinc compounds with aryl- and alkenyl halides and triflates. -------- 107
8. Direct preparation of organozinc compounds from alkyl bromides in the presence of LiCl. ------------ 112
9. Summary and outlook -------------------------------------------------------------------------------------------------- 117
Experimental Part
10. General considerations------------------------------------------------------------------------------------------------ 126
11. Typical procedures (TP) ---------------------------------------------------------------------------------------------- 127
11.1. Typical procedure for the condensation of cycloalkanones with aliphatic aldehydes (TP1).------- 128
11.2 Typical procedure for the Luche reduction of enones (TP2). -------------------------------------------- 128
11.3 Typical procedure for the enzymatic kinetic resolution of cyclic allylic alcohols with Amano lipase (PS-A)
(TP3). ---------------------------------------------------------------------------------------------------------------------- 128
11.4 Typical procedure for the preparation and in situ rearrangement of allyl diphenylphosphinites (TP4).128
11.5 Typical procedure for the hydroboration of allyldiphenylphosphine oxides with 9-BBN and oxidation
with m-CPBA (TP5). ----------------------------------------------------------------------------------------------------- 128
11.6 Typical procedure for the reduction of phosphine oxides by Ti(IV)-PMHS (TP6). ------------------------ 129
11.7 Typical procedure for the synthesis of bis-phosphine boranes from phosphine-borane alcohols (TP7).129
11.8 Typical procedure for the deprotection of a phosphine borane with N,N’-bis-(3-aminopropyl)piperazine
(TP8). ---------------------------------------------------------------------------------------------------------------------- 129
11.9 Typical procedure for the hydrogenation of a diphenylphosphine oxide over Raney Ni (TP9).--------- 130
11.10 Typical procedure for the cross-coupling of silylzinc reagents with aryl triflates (TP10).-------------- 130
11.11 Typical procedure for the cross-coupling of tris-(trimethylsilyl)aluminium with aryl triflates (TP11).130
11.12 Typical procedure for the conversion of aryldimethylphenylsilanes into aryl iodides (TP12). --------- 130
11.13 Typical procedure for the conversion of aryldimethylphenylsilanes into arylboronic esters (TP13). - 131
11.14 Typical procedure for the halogene-magnesium exchange reaction in the presence of LiCl (TP14). - 131
11.15 Typical procedure for the preparation of S-aryl-N,N-dimethylditiocarbamates from arylmagnesium
halides (TP15). ----------------------------------------------------------------------------------------------------------- 131
11.16 Typical procedure for the preparation of N,N-dimethylditiocarbamates from organozinc compounds
(TP16).--------------------------------------------------------------------------------------------------------------------- 131
11.17 Typical procedure for the Ni-catalyzed cross-coupling reaction of arylzinc halides with aryl
electrophiles (TP17).----------------------------------------------------------------------------------------------------- 131
11.18 Typical procedure for the Ni-catalyzed cross-coupling reaction of arylzinc halides with alkenyl
electrophiles (TP18).----------------------------------------------------------------------------------------------------- 132
11.19 Typical procedure for the insertion of Zn into alkyl bromides in the presence of LiCl and reaction with
an electrophile (TP19). -------------------------------------------------------------------------------------------------- 132
11.20 Typical procedure for the asymmetric Rh-catalyzed hydrogenation of methyl acetamidocinnamate and
methyl acetamidoacrylate (TP20). ------------------------------------------------------------------------------------- 132
11.21 Typical procedure for the asymmetric Rh-catalyzed hydrogenation of dimethyl itaconate (TP21).--- 132
10