Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue
Key words palladium(0) - asymmetric catalysis - difunctionalization - 1,3-dienes - cascade reaction
1
Introduction
Liu-Zhu Gong (left) was born in October 1970 in Henan, China. He graduated from Henan Normal University
(1993) and received his Ph.D. (2000) from the Institute of Chemistry, Chinese Academy
of Sciences. He was a visiting scholar (Joint Ph.D. graduate student program) at the
University of Virginia and an Alexander von Humboldt Research Fellow at the University
of Munich (2003–2004). He was appointed an associate professor of Chengdu Institute
of Organic Chemistry, Chinese Academy of Sciences in 2000 and was promoted to a full
professor in 2001. Since 2006, he has been a full professor of University of Science
and Technology of China. He was appointed the Cheung Kong Scholar Professor of organic
chemistry in 2007. His research interests include organo-/transition-metal cooperative
and relay catalysis, asymmetric multicomponent and cascade reactions, catalytic asymmetric
functionalization of allylic C–H bonds, and enantioselective total synthesis of natural
products.
Xiang Wu (right) was born in 1982 in Jiangsu, China. He received his B.Sc. degree in chemistry
from Nankai University in 2005. He completed his Ph.D. studies in organic chemistry
(2005–2010) at the same institution under the supervision of Professor Wei-dong Z.
Li. He worked in Suzhou Novartis Pharma Technology Co., Ltd from 2010 to 2012. He
was a postdoctoral researcher under the guidance of Professor Liu-Zhu Gong at University
of Science and Technology of China (2012–2014) and Professor Gong Chen at the Pennsylvania
State University (2014–2015). Since 2015, he has been an associate professor at Hefei
University of Technology and his research interests are in palladium-catalyzed functionalization
of dienes and oxidative asymmetric cycloaddition.
Buta-1,3-diene, which is important industrially as a monomer in the production of
synthetic rubber, is produced from steam crackers on a scale of more than 10 million
tons per year worldwide.[1 ] The last several decades have witnessed the proliferation of fundamentally important
and synthetically significant methods by functionalizing 1,3-diene and its derivatives,[2 ] which have been prevalently applied in the natural product synthesis, medicinal
chemistry and materials science.[3 ] The difunctionalization of 1,3-dienes provides a wide spectrum of structurally diverse
and densely functionalized chemicals with great potential in organic synthesis, and
has hence been considered a powerful strategy in synthetic organic chemistry.[4 ] In the difunctionalization of 1,3-dienes, it is a significant challenge to control
the regioselectivity toward 1,2- or 1,4-addition because of the various coordination
and insertion modes conceivable for a transition-metal catalyst. In recent years,
with the development of organometallic chemistry, transition-metal catalyst (palladium,
copper, nickel and more) enabled difunctionalization of 1,3-dienes has been reported,
frequently and continuously. Both Pd(0) and Pd(II) catalysts are able to promote difunctionalization
reaction of carbon–carbon double bonds. The palladium(II) coordinated with one of
double bonds of 1,3-diene undergoes a nucleopalladation with a nucleophile (Nu1
– ) in a Wacker type process to generate a π-allyl palladium intermediate A , which can then undergo a substitution reaction with another nucleophile (Nu2
– ) to afford either a 1,2- or a 1,4-product, and to release the Pd(0), which is oxidized
into catalytically active Pd(II) for the next catalytic cycle (Scheme [1 ], eq. 1). The palladium(0) complex has also been shown to enable various difunctionalization
reactions after it undergoes an oxidative addition to a high oxidation state compound
and a subsequent Heck insertion of the 1,3-diene to form a π-allyl palladium species
B , which ultimately reacts with a nucleophile to generate a 1,2- or 1,4-addition-like
product (Scheme [1 ], eq. 2).
Scheme 1 Pd-catalyzed difunctionalization of 1,3-dienes
Considering that a variety of excellent reviews have summarized the metal-catalyzed
enantioselective difunctionalization of the 1,2- or 1,4- positions of 1,3-dienes,[4e ]
[4f ]
[5 ] this short review mainly focuses on highlighting Pd(0)-catalyzed difunctionalization
of 1,3-dienes. As shown in Scheme [2 ], the Pd(II) intermediate I , generated from an oxidative addition reaction of a Pd(0) complex to an R-X, undergoes
a Heck insertion reaction to give an allylic palladium intermediate II , which will be able to undergo isomerization to form a π-allyl palladium intermediate
III . The π-allyl palladium species III then participates in an allylic alkylation reaction with a stabilized carbon nucleophile
by direct back-side attack at one of the allylic terminuses, principally giving rise
to either a 1,2-product or a 1,4-product and releasing Pd(0) (Path A). Alternatively,
a transmetalation at the palladium of intermediate III gives π-allyl palladium intermediate IV , which then undergoes a reductive elimination to generate a 1,2-product or a 1,4-product
and release Pd(0) (Path B).
Scheme 2 Putative catalytic cycle for the Pd(0)-catalyzed difunctionalization of 1,3-dienes
2
Amination
2.1
Three-Component Arylation or Vinylation/Amination
The first example of Pd(0)-catalyzed three-component difunctionalization of 1,3-dienes
was reported by Heck’s group in 1978.[6 ] They initially planned to synthesize conjugated dienes from bromobenzene or 2-bromopropene
with isoprene by palladium-catalyzed arylation; unexpectedly, regiospecific 1,4-difunctionalized
allylic amines 1 and 2 were obtained when a large excess of secondary amine (piperidine or morpholine) was
employed in the reaction (Scheme [3 ], eqs. 1 and 2).[6 ] In contrast to acyclic dienes, 1,3-cyclohexadiene provided both 1,2- and 1,4-products
(Scheme [3 ], eqs. 3 and 4).[7 ]
[8 ]
Scheme 3 Three-component arylation or vinylation/amination
Moreover, Dieck and co-workers also found that a broad scope of amines such as ethyl
amine, diethyl amine, n -butylamine, tert -butylamine and pyrrolidine could work as nucleophiles to participate in the arylation/amination
and to yield 1,2- and 1,4-products (Scheme [4 ]).[9 ]
Scheme 4 Amine nucleophiles for the three-component arylamination
2.2
Arylation/Intramolecular Amination
At the same time, Dieck’s group reported a cascade arylation and intramolecular amination
reaction of o -iodoaniline with isoprene and 1,3-cyclohexadiene, to generate 2-isopropenyl-2,3-dihydroindole
3 (72%) and la,3,4,4a-tetrahydrocarbazole 4 (70%), respectively (Scheme [5 ]).[9 ]
Scheme 5 Arylation/intramolecular amination cascade
Larock and co-workers then developed an even more efficient heteroannulation reaction
of 1,3-dienes with 2-iodophenyltosyl amide, leading to dihydroindole 5 and tetrahydrocarbazole 6 in higher yields (Scheme [6 ]).[10 ] 2-Iodobenzylic tosyl amides also turned out to be excellent substrates to furnish
six-membered nitrogeneous heterocycles 7 .
Scheme 6 Arylation/intramolecular amination cascade to generate dihydroindole, tetrahydrocarbazole
and six-membered ring nitrogen heterocycles
Inspired by Dieck[9 ] and Larock’s[10 ] pioneering work, Han and co-workers described the first Pd(0)-catalyzed enantioselective
heteroannulation of 1,3-dienes with 2-iodoanilines (Scheme [7 ]).[11 ] Chiral indolines 8 were obtained in up to 83% yield and with fairly good enantioselectivities of up
to 87% ee. The employment of a BINOL-derived phosphoramidite ligand L1 bearing electron-withdrawing substituents is the key to delivering high enantioselectivity.
Scheme 7 Enantioselective cascade arylation/intramolecular amination reaction to access chiral
indolines assisted by chiral BINOL-derived phosphoramidite ligand
In 1999, Helmchen reported an enantioselective tandem Heck/intramolecular allylic
amination reaction using amino group tethered 1,3-dienes and aryltriflates as substrates
(Scheme [8 ]).[12 ] Chiral PHOX ligand L2 allowed the reaction to give chiral piperidine 10 with 80% ee. Compared to the aryliodides, aryltriflates 9 gave higher enantioselectivities, but required prolonged reaction time of 10 days.
Scheme 8 Enantioselective arylation/intramolecular amination for the synthesis of chiral piperidine
2.3
Intramolecular Arylation or Vinylation/Amination
In 1989, Grigg and co-workers found that dienamide group tethered phenyliodide 11 could undergo a Pd(0)-catalyzed intramolecular 5-exo -trig cyclization on a proximate diene functionality to generate π-allyl-palladium
species, which was subsequently captured by secondary amines, including morpholine,
piperidine or 1,2,3,4-tetrahydroisoquinoline, giving 1,4-products 12 in 40–60% yield (Scheme [9 ]).[13 ]
In 1993, Shibasaki’s group reported a Pd/BINAP-catalyzed intramolecular asymmetric
Heck reaction/allylic amination reaction (Scheme [10 ]).[14 ] Under the catalysis of a chiral complex formed in situ from Pd(OAc)2 and (S )-BINAP, prochiral alkenyl triflate 13 and benzylamine underwent a vinylamination to give a bicyclic product 14 with three continuous chiral centers in 76% yield and with 81% ee.
Scheme 9 Racemic intramolecular arylation/amination
Scheme 10 Enantioselective intramolecular vinylation/amination
The Pd-catalyzed intramolecular arylamination has been applied in the total synthesis
of a natural product by Overman and co-workers (Scheme [11 ]).[15 ] The catalytic asymmetric Heck cyclization/allylic amination reaction of (2Z )-2,4-hexadienamide tethered diketopiperazine precursor 15 in the presence of Pd2 (dba)3 and (S )-BINAP produced pentacyclic products 16 and 17 in 6:1 ratio and 28% combined yield. Interestingly, when ligand (R )-BINAP was used, a 1:6 diastereomeric mixture of pentacyclic products 16 and 17 was obtained with similar efficiency. However, the use of tri-o -tolylphosphine as the ligand enabled (2E )-2,4-hexadienamide18 to give a 1:1 mixture of pentacyclic products 19 and 20 , attributed to the anti -capture of the initially produced η3 -allylpalladium intermediate. Removal of the SEM group from the product 19 provided optically pure (–)-spirotryprostatin B. Notably, the other three stereoisomers
could also be obtained by following a similar procedure.
Scheme 11 Enantioselective intramolecular arylamination for the total synthesis (–)-spirotryprostatin
B
2.4
Aminomethylamination
To expand the application of the aminal activation concept,[16 ] Huang and co-workers recently described a highly enantioselective aminomethylamination
reaction of 1,3-dienes with aminals enabled by a chiral palladium complex of BINOL-derived
chiral diphosphinite L3 (Scheme [12 ]).[17 ] The reaction proceeded through a cascade reaction sequence of C–N bond activation
(P1 ), aminomethylation (P2 ), and asymmetric allylic amination reaction (P3 ), giving synthetically useful chiral 1,3-diamines 21 with high regio- and enantioselectivity (Scheme [12 ]).
Scheme 12 Asymmetric intermolecular aminomethylamination of 1,3-dienes with an aminal
2.5
Diamination
Chiral vicinal diamine is a structural motif prevalently found in numerous biological
compounds and appears to be a core structural element of chiral auxiliaries and ligands
that have been widely applied in asymmetric synthesis.[18 ] Metal-mediated or catalyzed diamination of olefins constitutes one of the most efficient
approaches to access the skeleton.[19 ]
In 2007, Shi and co-workers reported that Pd(PPh3 )4 could catalyze the diamination of a variety of conjugated dienes using di-tert -butyldiaziridinone 23 as nitrogen source to give the racemic imidazolidinones 24 in high yields (Scheme [13 ]).[20 ] In this reaction, the palladium complex first undergoes an oxidative addition to
the N−N bond of diaziridine to form a diamido Pd(II) species Int-1 , which then reacts with the 1,3-diene to give a π-allyl Pd species Int-2 through a migratory insertion to the double bond and a subsequent reductive elimination
to give diamination product 24 (Scheme [13 ]).[21 ]
[22 ] Among these elementary reactions, the migratory insertion of the double bond of
1,3-diene to the diamido Pd(II) intermediate Int-1 builds up the initial stereogenic center and the reductive elimination of π-allyl
Pd species Int-2 leads to another one. Both events involve the palladium complex. Thus, the enantioselective
version could in principal be accessed by exploiting chiral phosphine ligands.[21 ] Shi and co-workers found that a palladium complex adorned with tetramethylpiperidine-derived
and binol-based phosphoramidite ligand L4 enabled asymmetric diamination of 1,3-dienes to furnish the corresponding products
25 in good yields and with high levels of regio-, diastereo-, and enantioselectivity
(Scheme [14 ]). Notably, the diamination takes place predominantly at the internal double bond
of the 1,3-dienes.[23 ]
Scheme 13 Diamination of 1,3-dienes
Scheme 14 Enantioselective diamination for the synthesis of chiral imidazolidinones assisted
by a tetramethylpiperidine-derived phosphorus amidite ligand
Shi further found that N-heterocyclic carbine (NHC)-Pd(0) complexes were also able
to efficiently promote the diamination of 1,3-dienes with di-tert -butyldiaziridinone 23 (Scheme [15 ]).[24 ] Moreover, the chiral NHC-Pd(0) complex [Pd1] Cl was found to be more catalytically active than other tested ligands for the diamination.[25 ]
Scheme 15 NHC-Pd(0)-catalyzed asymmetric diamination
Di-tert -butylthiadiaziridine 1,1-dioxide 26 is also an active substrate to undergo Pd-catalyzed diamination of 1,3-dienes. Optically
active cyclic sulfamides 27 were manufactured in up to 98% yield and with up to 93% ee from the reaction of 1,3-dienes
with 26 enabled by palladium catalyst generated from Pd2 (dba)3 and chiral phosphoramidite L5 (Scheme [16 ]).
Scheme 16 Enantioselective diamination with di-tert -butylthiadiaziridine 1,1-dioxide
2.6
Hydroamination
Hydroamination refers to the direct addition of amines to unsaturated hydrocarbons,
leading to amines.[26 ] 1,3-Dienes and primary or secondary amines could undergo hydroamination smoothly
in the presence of Pd(0) and appropriate ligands, in which η3 -C3 H5 Pd(II) complex are used widely as catalyst precursors. In the catalytic cycle (Scheme
[17 ]), an amine attacks the original η3 -C3 H5 Pd salt to generate an ammonium salt 29 and Pd(0). Oxidative protonation with the ammonium salt then forms a transient Pd-H
Int-3 . Diene migratory insertion to the Pd-H intermediate initially leads to a Pd-σ-allyl
Int-4 , which may isomerize into π-allyl intermediate Int-5 . The subsequent attack by the amine generates a Pd0 -allylic ammonium complex Int-6 , which releases the product 28 and regenerates Pd(0).
Scheme 17 Catalytic cycle for the hydroamination of 1,3-dienes
In 2001, the Hartwig lab showed that aryamines could be added to cyclohexene in the
presence of [Pd(η3 -C3 H5 )Cl]2 and Trost ligand L6 to give chiral 1,4-products 30 with up to 95% ee (Scheme [18 ]).[27 ]
Scheme 18 Enantioselective hydroamination with symmetrical cyclic dienes
Cationic η3 -C3 H5 palladium complexes [Pd2] OTf, prepared by the treatment of [Pd(η3 -C3 H5 )Cl]2 with 1,2-diaryl-3,4-bis[(2,4,6-tri-tert -butylphenyl)phosphinidene]cyclobutenes and AgOTf in CH2 Cl2 , rendered the hydroamination of 1,3-cyclohexadiene with aniline at room temperature
to give the corresponding 1,2-addition products 31 in high yields (Scheme [19 ]).[28 ] The use of diphosphinidenecyclobutene ligand with sp2 -hybridized phosphorus atoms having strong-acceptor ability is critical for the catalytic
activity.
Scheme 19 [Pd2]OTf-catalyzed racemic hydroamination
Beller and co-workers reported a 1,4-hydroamination acyclic and cyclic dienes catalyzed
by Pd(cod)Cl2 in combination with a bidentate phosphorus ligand DPEphos L7 (Scheme [20 ]).[29 ] The reaction proceeds in good yields and with high regioselectivity.
Scheme 20 Racemic 1,4-hydroamination of acyclic or cyclic dienes
In 2017, Malcolmson et al. established an enantioselective hydroamination of aliphatic
amines with acyclic 1,3-dienes, generating chiral allylic amines 32 in up to 94% ee (Scheme [21 ]).[30 ] Chiral PHOX ligand L8 involving an electron-deficient phosphine not only shows high reactivity in the transformation
but also plays a special role in achieving high site and enantioselectivity for the
1,2-addition product. Notably, more electron-rich substituents on the diene have a
dramatic effect on the formation of the 1,2-product.
Scheme 21 Enantioselective hydroamination of aliphatic amines with acyclic 1,3-dienes
Scheme 22 Enantioselective hydroamination of 1,4-disubstituted acyclic internal 1,3-dienes
Very recently, the same group reported a highly enantio- and regioselective Pd(0)-catalyzed
hydroamination of 1,4-disubstituted acyclic internal 1,3-dienes, which are considered
even more challenging substrates (Scheme [22 ]).[31 ] A variety of secondary aliphatic amines, indoline, and primary anilines undergo
the asymmetric 1,2-hydroamination reaction with a diverse spectrum of aryl/alkyldisubstituted
dienes as well as sterically differentiated alkyl/alkyldisubstituted dienes, generating
allylic amines 33 bearing various α-alkyl substituents in up to 78% yield, with >98:2 rr, and 97% ee.
3
Boration
The boration of 1,3-dienes has received a great deal of attention because it generates
a diverse range of alkyl boronates, which are important intermediates and building
blocks in synthetic organic chemistry.[32 ] Fe,[33 ] Cu[34 ] or Ir[35 ]-catalyzed boration of 1,3-dienes has been investigated intensively by several groups;
however, the Pd(0)-catalyzed variants are relatively rare.
3.1
Hydroboration
The preparation of allylic boronates 36 from a 1,4-hydroboration of 1,3-dienes was initially reported by Suzuki’s group in
1989.[36 ] Under the catalysis of Pd(PPh3 )4 , the hydroboration of buta-1,3-diene, isoprene, myrcene or 2,3-dimethylbuta-1,3-diene
with catecholborane (1,3,2-benzodioxaborole) 35 proceeds smoothly to provide 2-[(Z )-2-alkyl-2-butenyl]-1,3,2-benzodioxaboroles 36a –d with very high regio- and stereoselectivity, which are able to undergo carbonyl allylation
with benzaldehyde to produce homoallylic alcohols 37 in high yields and diastereoselectivities (Scheme [23 ]).
Scheme 23 Hydroborations of 1,3-dienes
3.2
Arylboration
Recently, Gong and co-workers reported a stereo- and regioselective multicomponent
carbonyl allylation reaction of buta-1,3-dienes, aryldiazonium tetrafluoroborates,
and aldehydes in the presence of octaphenyl-2,2′-bi(1,3,2-dioxaborolane) [B2 (Pin)2 ], enabled by the combined catalysis of palladium acetate and chiral anion phase transfer,
favoring the assembly of chiral Z -configured homoallylic alcohols 38 in high yields and with excellent levels of enantioselectivity (Scheme [24 ]).[37 ] The key chiral allylboronate intermediate Int-7 , which then undergoes the asymmetric allylborylation of aldehydes to give homoallylic
alcohols, is initially generated from the arylborylation of a 1,3-diene with an aryldiazonium
tetrafluoroborates and B2 (Pin)2 rendered by the palladium and chiral anion phase-transfer combined catalysis.
Scheme 24 Enantioselective alkynylboration with buta-1,3-dienes and alkynyl bromides
3.2
Alkynylboration
To extend the scope of the palladium and chiral anion phase-transfer combined catalysis
for the difunctionalization of 1,3-dienes, Gong and co-workers established a multicomponent
carbonyl allylation reaction of buta-1,3-dienes, alkynyl bromides, and aldehydes with
octaphenyl-2,2′-bi(1,3,2-dioxaborolane) (Scheme [25 ]).[38 ] The alkynyl palladium phosphate Int-8 generated in situ from the metathesis reaction of a chiral silver phosphate and the
alkynyl palladium bromide turns out to be a key intermediate that controls the stereoselectivity
of chiral allylboronate intermediate Int-9 .
Scheme 25 Enantioselective alkynylboration with buta-1,3-dienes and alkynyl bromides
4
Carbonation
In addition to heteroatom nucleophiles, stabilized carbanions such as – CH(CN)2 , – CH(CN)CO2 R or – CH(CO2 R)2 have been widely employed in the Pd-catalyzed carbonation of 1,3-dienes.
4.1
Vinyl or Arylation/Alkylation
In 1983, Dieck and co-workers reported the first vinylalkylation reaction of 1,3-dienes
with dimethyl sodiomalonate and 1-bromo-2-methylpropene catalyzed by palladium complex
formed from Pd(OAc)2 and PPh3 , to give the corresponding 1,4-selective product 39 , albeit in moderate yield (Scheme [26 ]).[9 ]
Scheme 26 Vinylalkylation with 1-bromo-2-methylpropene
In 1987, Takahashi and co-workers described a Pd-catalyzed three-component arylalkylation
of buta-1,3-diene with aryliodide and malononitrile or methyl cyanoacetate, allowing
for the generation of the corresponding 1,4-products 40 and 41 with iodobenzene and buta-1,3-diene in moderate yields (Scheme [27 ]).[39 ]
Scheme 27 Arylalkylation with iodobenzene
4.2
Intramolecular Arylation or Vinylation/Alkylation
Grigg and co-workers demonstrated that the sodiomalononitrile could attack the π-allyl-palladium
species, which is catalytically generated from an intramolecular 5-exo -trig cyclization on a proximate diene mediated with Pd complex, to afford the corresponding
regiospecific 1,4-product 42 in 60% yield (Scheme [28 ]).[13 ]
Scheme 28 Intramolecular arylalkylation
By using BINAP as a chiral ligand, Shibasaki established an intramolecular asymmetric
Heck insertion and allylic alkylation cascade reaction (Scheme [29 ]).[40 ] An optically active functionalized bicyclo[3.3.0]octane 43 could be feasibly accessed by this reaction and was used as a chiral building block
for the first catalytic asymmetric total synthesis of (–)-∆9(12) -capnellene. Interestingly, the addition of sodium bromide improved the enantioselectivity
without erosion of the chemical yield in all cases by preventing counteranion exchange
between the triflate anion and the enolate anion by coordination with sodium enolate.
Scheme 29 Enantioselective intramolecular arylalkylation for the total synthesis of (–)-∆9(12) -capnellene
4.3
Arylation/Intramolecular Alkylation
In parallel with the development of heteroannulation of 1,3-dienes,[10 ] Larock and co-workers also accomplished an intramolecular carboannulation of 1,3-dienes
with aryl iodides to give indanes 44 and tetralins 45 in high yields (Scheme [30 ]).[41 ] In addition to malonate-type nucleophiles, other carbon nucleophiles α to an ester,
a ketone or a nitrone functionality were also tolerated, as exemplified by 46 –48 , to afford the corresponding products in good yields. Nevertheless, a palladium-catalyzed
annulation of 1,4-dienes using ortho -functionally substituted aryl halides was also developed by the same group.[42 ]
Scheme 30 Arylation/intramolecular alkylation for the synthesis of indane and tetralin
The enantioselective carboannulation of 1,3-dienes and aryl iodides was very recently
established by Gong and co-workers. The use of chiral palladium complex of BINOL-based
phosphoramidite ligand L9 allowed the reaction to provide optically active indanes 49 in high yields and with excellent enantiomeric excesses (Scheme [31 ]).[43 ]
Scheme 31 Enantioselective carboannulation of 1,3-dienes and aryl iodides by using a BINOL-based
phosphoramidite ligand
4.4
Three-Component Arylation, Vinylation or Alkylation
In 2011, Sigman and co-workers reported a three-component coupling reaction of vinyl
triflates and boronic acids with terminal 1,3-dienes catalyzed by palladium to give
1,2-vinylarylation product 50 (Scheme [32 ]).[44 ] The Pd-π-allyl intermediate int-10 tends to undergoing transmetalation with a boronic acid derivative rather than β-hydride
elimination, after reductive elimination to give the products 50 .
Scheme 32 Three-component vinylarylation
In 2015, the same group reported a three-component coupling of isoprene, an alkenyl
triflate, and styrenylboronic acid to produce skipped polyenes from simple chemical
feedstocks (Scheme [33 ]).[45 ]
[46 ] However, complex isomeric product mixtures 51 –53 were always obtained because of the difficult-to-control migratory insertion of isoprene
into a Pd-alkenyl bond, while a good site selectivity of 1,4-addition (for the generation
of 53 ) can be achieved by using easily accessible pyrox ligand L10 .
Subsequently, Sigman and co-workers reported an intermolecular 1,2-diarylation reaction
of 1,3-dienes with aryldiazonium salts and aryl boronic acids, allowing the installation
of two different aryl groups (Scheme [34 ]).[47 ] In the presence of a chiral bicyclo[2.2.2]octadiene ligand L11 , a good enantiomeric excess was obtained, albeit in rather low yield.
Scheme 33 Three-component coupling of isoprene, an alkenyl triflate, and styrenylboronic acid
for the synthesis of skipped polyenes
Scheme 34 Asymmetric 1,2-diarylation
In 2015, Gong and co-workers successfully established a highly enantioselective three-component
coupling of 1,3-dienes with aryl iodines and stabilized carbon nucleophiles (sodium
dialkyl malonates) (Scheme [35 ]).[48 ] A H8 -BINOL-based phosphoramidite L12 turned out to be the most effective chiral ligand, which not only provides high catalytic
activity, but is also able to efficiently control the regio- and stereoselectivity.
Scheme 35 Enantioselective three-component coupling of 1,3-dienes with aryl iodines and sodium
dialkyl malonates
4.5
Others
Yoshida and Ihara reported a cascade insertion–ring expansion reaction of 1,3-dienylcyclobutanols
with aryl iodides to generate (Z )-2-(3-aryl-1-propenyl)cyclopentanones 54 in a stereospecific manner (Scheme [36 ]).[49 ] In the reaction, an arylpalladium complex formed from aryl iodide with palladium(0)
undergoes a Heck insertion reaction with 1,3-dienyl moiety to give an allylic palladium
intermediate Int-11 . The Int-11 reacts with a base to form a zwitterionic π-allylpalladium intermediate Int-12 , which subsequently undergoes a ring rearrangement to furnish a ring-expanded product
54 and regenerate the palladium(0) catalyst.
Scheme 36 Cascade insertion-ring expansion reaction of 1,3-dienylcyclobutanols with aryl iodides
for the synthesis of (Z )-2-(3-aryl-1-propenyl)cyclopentanones
Recently, Luan and co-workers described a Pd-catalyzed dearomatization reaction of
phenol-derived biaryls with 1,3-dienes to generate spirocyclic compounds 55 in good yields and with excellent chemo- and regioselectivity (Scheme [37 ]).[50 ] The reaction proceeds through a reaction sequence of oxidative addition (P4 , Scheme [38 ]) to the C–I bond, regioselective olefin insertion (P5 ), and allylative dearomatization (P6 ).
Scheme 37 Dearomatization reaction of phenol-derived biaryls with 1,3-dienes for the synthesis
of spirocyclic compounds
Preliminary studies on the enantioselective version revealed that chiral phosphoramidite
ligand ent -L5 could allow the reaction to yield spirocyclic compounds with good enantioselectivities
(Scheme [38 ]).[50 ]
Scheme 38 Preliminary studies on asymmetric reaction
In a continuation of the asymmetric hydroamination of 1,3-dienes,[30 ]
[31 ] Malcolmson and co-workers recently described a highly efficient and enantioselective
intermolecular addition of activated C-pronucleophiles to acyclic 1,3-dienes enabled
by Pd catalysts ([Pd4] BF4 or [Pd5] BF4 ) bearing electronically deficient phosphines (Scheme [39 ]).[51 ] The 1,2-difunctionalized products 56 could be obtained in up to 96% yield and 95% ee.
Scheme 39 Enantioselective hydroalkylation
5
Hydrogenation
Sigman and co-workers recently reported the only example to date of regio- and stereoselective
1,2-vinylhydrogenation of terminal 1,3-dienes with enol triflates/nonaflates in the
presence of sodium formate (Scheme [40 ]).[52 ] Trapping of the π-allyl intermediate generated from the initial migratory insertion
of the diene with a hydride source allows access to structurally complex and synthetically
challenging stereodefined (E )- and (Z )-tri- and tetrasubstituted alkene building blocks 57 .
Scheme 40 1,2-Vinylhydrogenation of (E )- and (Z )-tri- and tetrasubstituted alkene
6
Oxygenation
Scheme 41 Arylation/intramolecular oxygenation to generate dihydrobenzofuran and isochroman
derivatives
Larock and co-workers created a Pd-catalyzed oxyannulation of 1,3-dienes with o -iodophenol substrates to give dihydrobenzofuran products (Scheme [41 ]).[10 ] Cyclohexa-1,3-diene, 1-butyl-1,3-butadiene and 2-methylbuta-1,3-diene underwent
facile intramolecular oxyannulation to deliver the corresponding dihydrobenzofurans
58 –60 in moderate yields (Scheme [41 ], eqs. 1–3). The reaction of o -iodophenol and isoprene affords compound 60 in reasonable yield (Scheme [41 ], eq. 3), although a minor amount of a regioisomer is observed. Phenols bearing electron-withdrawing
groups such as aldehydes and ketones generally give higher yields. Particularly, o -iodobenzyl alcohol can be employed to form isochroman derivative 62 (Scheme [41 ], eq. 4).
Recently, Han and co-workers realized an asymmetric version of the Pd-catalyzed difunctionalization
between o -iodobenzyl alcohol and arylbutadienes (Scheme [42 ]).[11 ] Under similar conditions in the synthesis of chiral indolines,[11 ] chiral isochromans 63a –d could be obtained with high enantioselectivities and moderate yields.
Scheme 42 Enantioselective arylation/intramolecular oxygenation to generate chiral isochromans
Scheme 43 Difunctionalization of 7-hydroxy-1,3-dienes with aryl bromides
In 2005, Yeh and co-workers reported a palladium-catalyzed difunctionalization of
7-hydroxy-1,3-dienes with aryl bromides (Scheme [43 ]).[53 ] The reaction proceeded through different paths depending on the structure of the
substrates. With cyclic 7-hydroxy-1,3-dienes 64 , the insertion of a C–C double bond into the Pd–O bond of the initially formed Pd(Ar)(OR)-olefin
complex Int-13 is predominant and results in the formation of 1,4-alkoxyarylation product 66 . In contrast, the reaction of acyclic 7-hydroxy-1,3-dienes 65 proceeded through the insertion of the double bond into either the Pd–C or the Pd–O
bond of the Pd(Ar)–(OR)–olefin intermediate Int-14 to afford 1,2-oxyarylation products 67 after reductive elimination. The difference in the formation of alkoxyarylation products
(1,4- vs. 1,2-alkoxyarylation) between cyclic and acyclic substrates actually arises
because the η1 -η3 -η1 allylic isomerization may be faster in the cyclic intermediate Int-15 than the acyclic intermediate Int-16 or Int-16′ for steric reasons.
To synthesize capnellenol, a catalytic asymmetric cascade Heck reaction and allylic
esterification was accomplished by Shibasaki.[14 ]
[54 ] Various ligands and solvents were screened to reveal that the chiral palladium complex
of (S )-BINAP delivered the best results in dimethyl sulfoxide (DMSO) (Scheme [44 ]).
Scheme 44 Enantioselective intramolecular vinyloxygenation
7
Silylation
Optically active allylsilanes are useful reagents in stereoselective organic synthesis,
because they are able to participate in asymmetric carbonyl or imine allylations with
highly efficient chirality transfer.[55 ] Increasing attention has been directed toward their asymmetric catalytic synthesis.
Among the methods to access chiral allylsilanes, the palladium-catalyzed asymmetric
hydrosilylation of 1,3-dienes has unique advantages, for example, using readily accessible
starting materials.[5 ] However, no breakthrough had been achieved in this field until recently.[56 ] The chiral monodentate phosphine L13 with a binaphthyl moiety was identified as the most efficient ligand for the asymmetric
hydrosilylation of cyclic 1,3-dienes whereas the planar chiral ferrocenylmonophosphine
L14 with two ferrocenyl moieties turned out to be an efficient ligand for the reaction
involving linear 1,3-dienes (Scheme [45 ]).[5 ]
Scheme 45 Asymmetric hydrosilylation of 1,3-dienes
8
Conclusion and Outlook
In the past forty years, the palladium(0)-catalyzed difunctionalization reactions
of 1,3-dienes have made significant progress, culminating in a diverse range of transformations
that provide efficient way to assemble densely functionalized molecules from readily
available substances. Abundant availability of chiral ligands for the palladium(0)
catalysis has enabled switching the racemic reaction to an enantioselective version.
Nevertheless, the stereochemical control remains a formidable challenge in the difunctionalization
of 1,3-dienes, as indicated by the fact that many reactions are still not enantioselective.
In addition, 1,3-diene components in these known processes are limited to aryl substituted
or terminal dienes. Either alkyl substituted or internal acyclic dienes have rarely
been reaction components in the asymmetric difunctionalization. Moreover, efficient
control of regioselectivity is another big deal in such transformations. Therefore,
new concepts, proper chiral ligands designed for Pd catalysis, and the development
of new transformations for building up structural complexity will be future focuses
in the difunctionalization of 1,3-dienes.
