Palladium(0)-Catalyzed Difunctionalization of 1,3-Dienes: from Racemic to Enantioselective

Home , Carbonation, Oxidative addition, Spirotryprostatin B, Transmetalation

SYNTHESIS0039-78811437-210X Georg Thieme Verlag Stuttgart · New York 2019, 51, 122–134 short review 122 en

Syn thesis X. Wu, L.-Z. Gong Short Review

Palladium(0)-Catalyzed Difunctionalization of 1,3-Dienes: From Racemic to Enantioselective

Xiang Wua Liu-Zhu Gong*b,c 0000-0001-6099-827X Pd(0) Nu Nu Pd(0) a PdLn Anhui Province Key Laboratory of Advanced Catalytic R or R' R R Materials and Reaction Engineering, School of Chemistry and Chemical R'-X R – Nu Engineering, Hefei University of Technology, Hefei 230009, P. R. of China R' R' b Department of Chemistry, University of Science and Technology of 1,2-product 1,4-product China, Hefei 230026, P. R. of China X = Br, I, OTf, ONf, N, N + Nu = N, B, C, H, O, Si c Collaborative Innovation Center of Chemical Science and Engineering, 2 R' = H, N, C Tianjin 300072, P. R. of China [email protected]

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Received: 17.10.2018 Accepted after revision: 18.10.2018 Published online: 15.11.2018 DOI: 10.1055/s-0037-1610379; Art ID: ss-2018-z0700-sr License terms:

Abstract 1,3-Dienes are easily accessible chemicals that participate in a series of reactions acting on the carbon–carbon double bonds. Cata- lytic difunctionalization of 1,3-dienes provides a wide scope of functionalized chemicals. Pd(0) catalysts provide a diverse set of principles for the creation of asymmetric catalytic reactions, which are initiated with the oxidative addition and then undergo insertion reaction with Liu-Zhu Gong (left) was born in October 1970 in Henan, China. He one of double bonds of the 1,3-diene to become a π-allyl palladium graduated from Henan Normal University (1993) and received his Ph.D. species that is reactive toward nucleophilic attack. This review summa- (2000) from the Institute of Chemistry, Chinese Academy of Sciences. rizes typical advances on the Pd(0)-catalyzed difunctionalization of 1,3- He was a visiting scholar (Joint Ph.D. graduate student program) at the dienes in recent decades, particularly emphasizing the concepts that University of Virginia and an Alexander von Humboldt Research Fellow enable the switch from a racemic reaction to an enantioselective ver- at the University of Munich (2003–2004). He was appointed an associ- sion. ate professor of Chengdu Institute of Organic Chemistry, Chinese Acad- 1 Introduction emy of Sciences in 2000 and was promoted to a full professor in 2001. 2 Amination Since 2006, he has been a full professor of University of Science and 3 Boration Technology of China. He was appointed the Cheung Kong Scholar Pro- 4 Carbonation fessor of organic chemistry in 2007. His research interests include orga- 5 Hydrogenation no-/transition-metal cooperative and relay catalysis, asymmetric 6 Oxygenation multicomponent and cascade reactions, catalytic asymmetric function- 7 Silylation alization of allylic C–H bonds, and enantioselective total synthesis of 8 Conclusion and Outlook natural products. Key words palladium(0), asymmetric catalysis, difunctionalization, Xiang Wu (right) was born in 1982 in Jiangsu, China. He received his 1,3-dienes, cascade reaction B.Sc. degree in chemistry from Nankai University in 2005. He complet- ed his Ph.D. studies in organic chemistry (2005–2010) at the same in- stitution under the supervision of Professor Wei-dong Z. Li. He worked 1 Introduction 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) Buta-1,3-diene, which is important industrially as a and Professor Gong Chen at the Pennsylvania State University (2014– monomer in the production of synthetic rubber, is pro- 2015). Since 2015, he has been an associate professor at Hefei Universi- duced from steam crackers on a scale of more than 10 mil- ty of Technology and his research interests are in palladium-catalyzed lion tons per year worldwide.1 The last several decades have functionalization of dienes and oxidative asymmetric cycloaddition. witnessed the proliferation of fundamentally important and synthetically significant methods by functionalizing densely functionalized chemicals with great potential in or- 1,3-diene and its derivatives,2 which have been prevalently ganic synthesis, and has hence been considered a powerful applied in the natural product synthesis, medicinal chemis- strategy in synthetic organic chemistry.4 In the difunction- try and materials science.3 The difunctionalization of 1,3- alization of 1,3-dienes, it is a significant challenge to con- dienes provides a wide spectrum of structurally diverse and trol the regioselectivity toward 1,2- or 1,4-addition because

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 123

Syn thesis X. Wu, L.-Z. Gong Short Review

of the various coordination and insertion modes conceiv- Pd(0) Nu RX + R R' Nu- able for a transition-metal catalyst. In recent years, with the R' development of organometallic chemistry, transition-metal 1,2-product 0 LnPd or RX catalyst (palladium, copper, nickel and more) enabled di- 1,4-product oxidative functionalization of 1,3-dienes has been reported, fre- X- addition Nu 1,2-product X or quently and continuously. Both Pd(0) and Pd(II) catalysts Pd L II n 1,4-product Ln Pd are able to promote difunctionalization reaction of carbon– R I R R' IV (Path A) carbon double bonds. The palladium(II) coordinated with R' (Path B) - one of double bonds of 1,3-diene undergoes a nucleopalla- Nu insertion – L dation with a nucleophile (Nu ) in a Wacker type process X L n X 1 Nu- n Pd Pd R to generate a π-allyl palladium intermediate A, which can R R' then undergo a substitution reaction with another nucleo- R' III II – phile (Nu2 ) to afford either a 1,2- or a 1,4-product, and to π-allyl release the Pd(0), which is oxidized into catalytically active formation Pd(II) for the next catalytic cycle (Scheme 1, eq. 1). The pal- Scheme 2 Putative catalytic cycle for the Pd(0)-catalyzed difunctional- ladium(0) complex has also been shown to enable various ization of 1,3-dienes 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 2 Amination palladium species B, which ultimately reacts with a nucleophile to generate a 1,2- or 1,4-addition-like product 2.1 Three-Component Arylation or Vinylation/Ami- (Scheme 1, eq. 2). nation

[O] Pd(0) The first example of Pd(0)-catalyzed three-component Nu2 Nu2 Pd(II) difunctionalization of 1,3-dienes was reported by Heck’s PdLn (1) R R or R 6 – Nu1 – Nu1 R Nu2 group in 1978. They initially planned to synthesize conju- Nu1 Nu1 A 1,2-Product 1,4-Product gated dienes from bromobenzene or 2-bromopropene with isoprene by palladium-catalyzed arylation; unexpectedly, Pd(0) Nu Nu Pd(0) regiospecific 1,4-difunctionalized allylic amines 1 and 2 PdLn (2) R or R' R R were obtained when a large excess of secondary amine R'-XR – Nu R' R' B 1,2-Product 1,4-Product (piperidine or morpholine) was employed in the reaction (Scheme 3, eqs. 1 and 2).6 In contrast to acyclic dienes, 1,3- Scheme 1 Pd-catalyzed difunctionalization of 1,3-dienes cyclohexadiene provided both 1,2- and 1,4-products (Scheme 3, eqs. 3 and 4).7,8 Considering that a variety of excellent reviews have Br summarized the metal-catalyzed enantioselective difunc- Pd(OAc)2 (1 mol%) P(o-tol)3 (2 mol%) tionalization of the 1,2- or 1,4- positions of 1,3-dienes,4e,4f,5 ++ N (1) N 100 °C, 48 h this short review mainly focuses on highlighting Pd(0)-cat- H 1 (300 mmol) 57% alyzed difunctionalization of 1,3-dienes. As shown in (10 mmol) O Pd(OAc)2 (1 mol%) P(o-tol)3 (2 mol%) Scheme 2, the Pd(II) intermediate I, generated from an oxi- ++ N (2) Br N 100 °C, 45 h dative addition reaction of a Pd(0) complex to an R-X, un- H O 2 (10 mmol) (300 mmol) dergoes a Heck insertion reaction to give an allylic palladi- 40% um intermediate II, which will be able to undergo isomeri- Br Pd(OAc)2 (1 mol%) PPh3 (2 mol%) N zation to form a π-allyl palladium intermediate III. The π- ++ + (3) N allyl palladium species III then participates in an allylic al- H 100 °C, 16 h N kylation reaction with a stabilized carbon nucleophile by 51% 2% direct back-side attack at one of the allylic terminuses, principally giving rise to either a 1,2-product or a 1,4-prod- Pd(OAc)2 (1 mol%) PPh3 (2 mol%) N uct and releasing Pd(0) (Path A). Alternatively, a transmeta- ++ + (4) Br N 100 °C, 24 h N lation at the palladium of intermediate III gives π-allyl pal- H ladium intermediate IV, which then undergoes a reductive 35% 15% elimination to generate a 1,2-product or a 1,4-product and Scheme 3 Three-component arylation or vinylation/amination release Pd(0) (Path B).

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 124

Syn thesis X. Wu, L.-Z. Gong Short Review

Moreover, Dieck and co-workers also found that a broad Inspired by Dieck9 and Larock’s10 pioneering work, Han scope of amines such as ethyl amine, diethyl amine, n-bu- and co-workers described the first Pd(0)-catalyzed enantio- tylamine, tert-butylamine and pyrrolidine could work as selective heteroannulation of 1,3-dienes with 2-iodoani- nucleophiles to participate in the arylation/amination and lines (Scheme 7).11 Chiral indolines 8 were obtained in up to to yield 1,2- and 1,4-products (Scheme 4).9 83% yield and with fairly good enantioselectivities of up to 87% ee. The employment of a BINOL-derived phosphora-

Nu midite ligand L1 bearing electron-withdrawing substitu- I Pd(OAc)2 (1 mol%) ents is the key to delivering high enantioselectivity. PPh3 (2 mol%) ++NuH 100 °C, 48 h + 2 Pd(OAc)2 (5 mol%) R NH 2 R2 L1 (15 mol%) R1 Nu = EtNH2, Et2NH R + n-BuNH , t-BuNH R 2 2 Nu 1 KHCO3, DME, 80 °C pyrrolidine I R N then AcCl, Et3N Ac 8 Scheme 4 Amine nucleophiles for the three-component arylamination O2N up to 87% ee Ar up to 83% yield

2.2 Arylation/Intramolecular Amination O P N O At the same time, Dieck’s group reported a cascade ary- Ar lation and intramolecular amination reaction of o-iodoani- L1 Ar = 3,5-(CF3)2C6H3 line with isoprene and 1,3-cyclohexadiene, to generate 2- isopropenyl-2,3-dihydroindole 3 (72%) and la,3,4,4a-tetra- Scheme 7 Enantioselective cascade arylation/intramolecular amina- hydrocarbazole 4 (70%), respectively (Scheme 5).9 tion reaction to access chiral indolines assisted by chiral BINOL-derived phosphoramidite ligand

In 1999, Helmchen reported an enantioselective tandem 125–130 °C N 39 h H Heck/intramolecular allylic amination reaction using amino I Pd(OAc)2 (1 mol%) PPh (2 mol%) 3 3 72% group tethered 1,3-dienes and aryltriflates as substrates 12 NH2 (Scheme 8). Chiral PHOX ligand L2 allowed the reaction to give chiral piperidine 10 with 80% ee. Compared to the 120–125 °C N 24 h H aryliodides, aryltriflates 9 gave higher enantioselectivities, 4 70% but required prolonged reaction time of 10 days.

Scheme 5 Arylation/intramolecular amination cascade Pd(OAc) (3 mol%) OTf 2 NBn NHBn L2 (6 mol%) + DMF, 100 °C, 10 d

Larock and co-workers then developed an even more ef- 9 10 80% ee, 47% yield ficient heteroannulation reaction of 1,3-dienes with 2-io- O dophenyltosyl amide, leading to dihydroindole 5 and tetra- N PPh2 hydrocarbazole 6 in higher yields (Scheme 6).10 2-Iodoben- Ph L2 zylic tosyl amides also turned out to be excellent substrates to furnish six-membered nitrogeneous heterocycles 7. Scheme 8 Enantioselective arylation/intramolecular amination for the synthesis of chiral piperidine Pd(OAc) (5 mol%) Ts NHTs 2 Na2CO3, n-Bu4NCl N + C4H9 2.3 Intramolecular Arylation or Vinylation/Amina- I DMF, 100 °C, 1 d C4H9 5 tion 84% Ts Pd(dba) (5 mol%) NHTs 2 Na2CO3, n-Bu4NCl N H In 1989, Grigg and co-workers found that dienamide + group tethered phenyliodide 11 could undergo a Pd(0)-cat- I DMF, 100 °C, 2 d H alyzed intramolecular 5-exo-trig cyclization on a proximate 6 87% diene functionality to generate π-allyl-palladium species, Pd(OAc)2 (5 mol%) PPh3 (5 mol%) Ts which was subsequently captured by secondary amines, in- NHTs Et3N, n-Bu4NCl N + C4H9 cluding morpholine, piperidine or 1,2,3,4-tetrahydroiso- I DMF, 80 °C, 2 d C4H9 7 quinoline, giving 1,4-products 12 in 40–60% yield (Scheme 81% 9).13 Scheme 6 Arylation/intramolecular amination cascade to generate di- In 1993, Shibasaki’s group reported a Pd/BINAP-cata- hydroindole, tetrahydrocarbazole and six-membered ring nitrogen het- lyzed intramolecular asymmetric Heck reaction/allylic ami- erocycles nation reaction (Scheme 10).14 Under the catalysis of a chi-

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 125

Syn thesis X. Wu, L.-Z. Gong Short Review

H O O O N N N N Pd2(dba)3·CHCl3 P(OAc)2 (5 mol%) BINAP NH H H I PPh3 (10 mol%) PMP, DMA + O N N N O + O H MeCN, 80 °C, 3 h N O 100 °C N Bn N O N O Bn 11 N O O SEM SEM I SEM 12 16 17 N = HN O HN 40–60% 15 (S)-BINAP 6:1 (28% yield) H HN (R)-BINAP 1:6 (26% yield) H O O O Scheme 9 Racemic intramolecular arylation/amination N N N NH Pd (dba) ·CHCl H H O 2 3 3 P(o-tol) , KOAc N N 3 O + O THF, 70 °C N O N O ral complex formed in situ from Pd(OAc) and (S)-BINAP, N O 2 SEM SEM I SEM prochiral alkenyl triflate 13 and benzylamine underwent a 20 18 19 vinylamination to give a bicyclic product 14 with three con- 1:1 (72% yield) O tinuous chiral centers in 76% yield and with 81% ee. N

H N Pd(OAc) (5 mol%) O 2 NHBn OTf (S)-BINAP (6.3 mol%) H NH Bn 2 N O DMSO, 20 °C, 2 h H Me Me spirotryprostatin B 13 14 81% ee, 76% yield Scheme 11 Enantioselective intramolecular arylamination for the total synthesis (–)-spirotryprostatin B Scheme 10 Enantioselective intramolecular vinylation/amination

R2 The Pd-catalyzed intramolecular arylamination has [Pd(allyl)Cl]2 (2.5 mol%) 1 OPAr2 been applied in the total synthesis of a natural product by R AgClO4 (5.5 mol%) L3 (5.5 mol%) NR2 OPAr2 15 + Overman and co-workers (Scheme 11). The catalytic 1 DCM, 10 °C, 48 h R NR2 2 21 R asymmetric Heck cyclization/allylic amination reaction of R2N NR2 up to 99% ee L3 2 (2Z)-2,4-hexadienamide tethered diketopiperazine precur- up to 93% yield R = 2,4,6-(i-Pr)3C6H2 Ar = 4-FC6H4 sor 15 in the presence of Pd2(dba)3 and (S)-BINAP produced NR pentacyclic products 16 and 17 in 6:1 ratio and 28% com- 2 Pd(0) NR2 R1 NR C–N bond bined yield. Interestingly, when ligand (R)-BINAP was used, 2 NR 21 2 activation a 1:6 diastereomeric mixture of pentacyclic products 16 asymmetric (P1) allylic amination – – R2N and 17 was obtained with similar efficiency. However, the (P3) R2N + use of tri-o-tolylphosphine as the ligand enabled (2E)-2,4- R2NCH2Pd hexadienamide18 to give a 1:1 mixture of pentacyclic prod- Ln X Pd ucts 19 and 20, attributed to the anti-capture of the initially R1 R1 NR 3 2 aminomethylation produced η -allylpalladium intermediate. Removal of the (P2) SEM group from the product 19 provided optically pure (–)- Scheme 12 Asymmetric intermolecular aminomethylamination of spirotryprostatin B. Notably, the other three stereoisomers 1,3-dienes with an aminal could also be obtained by following a similar procedure.

2.4 Aminomethylamination 2.5 Diamination

To expand the application of the aminal activation con- Chiral vicinal diamine is a structural motif prevalently cept,16 Huang and co-workers recently described a highly found in numerous biological compounds and appears to be enantioselective aminomethylamination reaction of 1,3- a core structural element of chiral auxiliaries and ligands dienes with aminals enabled by a chiral palladium complex that have been widely applied in asymmetric synthesis.18 of BINOL-derived chiral diphosphinite L3 (Scheme 12).17 Metal-mediated or catalyzed diamination of olefins consti- The reaction proceeded through a cascade reaction se- tutes one of the most efficient approaches to access the quence of C–N bond activation (P1), aminomethylation skeleton.19

(P2), and asymmetric allylic amination reaction (P3), giving In 2007, Shi and co-workers reported that Pd(PPh3)4 synthetically useful chiral 1,3-diamines 21 with high regio- could catalyze the diamination of a variety of conjugated and enantioselectivity (Scheme 12). dienes using di-tert-butyldiaziridinone 23 as nitrogen source to give the racemic imidazolidinones 24 in high

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 126

Syn thesis X. Wu, L.-Z. Gong Short Review yields (Scheme 13).20 In this reaction, the palladium com- O [Pd1]Cl (5 mol%) O plex first undergoes an oxidative addition to the N−N bond NaOtAm (15 mol%) 2 + N N R NN of diaziridine to form a diamido Pd(II) species Int-1, which R1 THF, 65 °C, 12 h R2 R1 then reacts with the 1,3-diene to give a π-allyl Pd species 23 up to 78% ee Ph Ph Int-2 through a migratory insertion to the double bond and Et Et up to 97% yield a subsequent reductive elimination to give diamination NN 21,22 product 24 (Scheme 13). Among these elementary reac- Et Pd Et tions, the migratory insertion of the double bond of 1,3-di- Cl ene to the diamido Pd(II) intermediate Int-1 builds up the [Pd1]Cl initial stereogenic center and the reductive elimination of π-allyl Pd species Int-2 leads to another one. Both events Scheme 15 NHC-Pd(0)-catalyzed asymmetric diamination involve the palladium complex. Thus, the enantioselective version could in principal be accessed by exploiting chiral Di-tert-butylthiadiaziridine 1,1-dioxide 26 is also an ac- phosphine ligands.21 Shi and co-workers found that a palla- tive substrate to undergo Pd-catalyzed diamination of 1,3- dium complex adorned with tetramethylpiperidine-derived dienes. Optically active cyclic sulfamides 27 were manufac- and binol-based phosphoramidite ligand L4 enabled asym- tured in up to 98% yield and with up to 93% ee from the re- metric diamination of 1,3-dienes to furnish the correspond- action of 1,3-dienes with 26 enabled by palladium catalyst ing products 25 in good yields and with high levels of regio- generated from Pd2(dba)3 and chiral phosphoramidite L5 , diastereo-, and enantioselectivity (Scheme 14). Notably, (Scheme 16). the diamination takes place predominantly at the internal 23 double bond of the 1,3-dienes. O O Pd2(dba)3 (2.5 mol%) O O S L5 (10 mol%) S + N N R NN toluene, 65 °C, 3 h O O Pd(PPh3)4 R (10 mol%) Ph 3 1 26 R R + N N 1 27 NN R O 2 C6D6, 65 °C up to 93% ee R P N 0.25–5 h R3 R2 up to 98% yield 22 23 24 O Ph O LnPd tBu tBu L5 N N R1

R3 R2 Scheme 16 Enantioselective diamination with di-tert-butylthiadiaziri- O 24 dine 1,1-dioxide t Bu tBu N N tBu O N R3 Pd 2 R Ln N 2.6 Hydroamination tBu Pd R1 Int-1

Int-2 R3 R1 Hydroamination refers to the direct addition of amines R2 to unsaturated hydrocarbons, leading to amines.26 1,3- Scheme 13 Diamination of 1,3-dienes Dienes and primary or secondary amines could undergo hydroamination smoothly in the presence of Pd(0) and ap- O O 3 Pd2(dba)3 (5 mol%) propriate ligands, in which η -C3H5 Pd(II) complex are used L4 (22 mol%) + N N R NN widely as catalyst precursors. In the catalytic cycle (Scheme C D , 65 °C, 12 h 6 6 3 R 17), an amine attacks the original η -C3H5 Pd salt to gener- 23 25 ate an ammonium salt 29 and Pd(0). Oxidative protonation O up to 95% ee P N up to 95% yield with the ammonium salt then forms a transient Pd-H Int-3. O Diene migratory insertion to the Pd-H intermediate initially leads to a Pd-σ-allyl Int-4, which may isomerize into π-allyl L4 intermediate Int-5. The subsequent attack by the amine 0 Scheme 14 Enantioselective diamination for the synthesis of chiral im- generates a Pd -allylic ammonium complex Int-6, which re- idazolidinones assisted by a tetramethylpiperidine-derived phosphorus leases the product 28 and regenerates Pd(0). amidite ligand In 2001, the Hartwig lab showed that aryamines could 3 be added to cyclohexene in the presence of [Pd(η -C3H5)Cl]2 Shi further found that N-heterocyclic carbine (NHC)- and Trost ligand L6 to give chiral 1,4-products 30 with up to Pd(0) complexes were also able to efficiently promote the 95% ee (Scheme 18).27 3 diamination of 1,3-dienes with di-tert-butyldiaziridinone Cationic η -C3H5 palladium complexes [Pd2]OTf, pre- 24 3 23 (Scheme 15). Moreover, the chiral NHC-Pd(0) complex pared by the treatment of [Pd(η -C3H5)Cl]2 with 1,2-diaryl- [Pd1]Cl was found to be more catalytically active than oth- 3,4-bis[(2,4,6-tri-tert-butylphenyl)phosphinidene]cy- er tested ligands for the diamination.25

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 127

Syn thesis X. Wu, L.-Z. Gong Short Review

R1 R2 Beller and co-workers reported a 1,4-hydroamination R1 R2 Pd(0) N R + N acyclic and cyclic dienes catalyzed by Pd(cod)Cl in combi- H L H 2 R 28 nation with a bidentate phosphorus ligand DPEphos L7 η3 29 Pd( -C3H5)X (Scheme 20). The reaction proceeds in good yields and R1R2NH Ln with high regioselectivity.

1 2 + – NR1R2 R R C3H5NH X L Pd0 29 n Pd(cod)Cl (5 mol%) H 2 R1 R NH2 L7 (5 mol%) H N 28 + R2 1 toluene, 100 °C, 10 h H R R2 II + LnPd 40–95% yield X– NHR1R2 X Int-3 H O R R P P 0 Int-6 LnPd Ph Ph Ph Ph L7

Ln X Pd Scheme 20 Racemic 1,4-hydroamination of acyclic or cyclic dienes X L H R1R2NH n Pd R H Int-4 R In 2017, Malcolmson et al. established an enantioselec- Int-5 tive hydroamination of aliphatic amines with acyclic 1,3- Scheme 17 Catalytic cycle for the hydroamination of 1,3-dienes dienes, generating chiral allylic amines 32 in up to 94% ee (Scheme 21).30 Chiral PHOX ligand L8 involving an electron-

3 deficient phosphine not only shows high reactivity in the [Pd(η -C3H5)Cl]2 (5 mol%) L6 (11 mol%) ArHN transformation but also plays a special role in achieving ArNH2 + THF, r.t., 120 h high site and enantioselectivity for the 1,2-addition prod- 30 uct. Notably, more electron-rich substituents on the diene up to 95% ee O O up to 87% yield have a dramatic effect on the formation of the 1,2-product. NH HN

[Pd(η3-C H )Cl] (2.5 mol%) P P 3 5 2 Ph2 L8 (5 mol%) 1 2 1 2 AgBF4 (6 mol%) R R L6 R R N R + N H CH2Cl2, 0–60 °C, 3–20 h R Scheme 18 Enantioselective hydroamination with symmetrical cyclic 32 94% ee dienes O

N PAr2 tBu clobutenes and AgOTf in CH Cl , rendered the hydroamina- Ar = 3,5-(CF3)2C6H3 2 2 L8 tion of 1,3-cyclohexadiene with aniline at room tempera- ture to give the corresponding 1,2-addition products 31 in Scheme 21 Enantioselective hydroamination of aliphatic amines with high yields (Scheme 19).28 The use of diphosphinidenecy- acyclic 1,3-dienes clobutene ligand with sp2-hybridized phosphorus atoms having strong-acceptor ability is critical for the catalytic ac- Very recently, the same group reported a highly enan- tivity. tio- and regioselective Pd(0)-catalyzed hydroamination of 1,4-disubstituted acyclic internal 1,3-dienes, which are MeO considered even more challenging substrates (Scheme Ar 22).31 A variety of secondary aliphatic amines, indoline, and P

F P [Pd3]BAr 4 (5 mol%) Et3N 1 2 Ar 1 2 R R R R R4 N N + 3 MeO R 4 H hexanes–Et2O (1:1), 22 °C R Ar = 2,4,6-tri-tert-butylphenyl R3

[Pd2] 33 [Pd2]OTf O up to 97% ee up to 78% yield + PhNH2 NHPh N PAr toluene, r.t., 5 h 2 up to 98:2 rr t Pd F 31 Bu BAr 4 89%

Ar = 3,5-(CF3)2C6H3 F Scheme 19 [Pd2]OTf-catalyzed racemic hydroamination [Pd3]BAr 4

Scheme 22 Enantioselective hydroamination of 1,4-disubstituted acyclic internal 1,3-dienes

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 128

Syn thesis X. Wu, L.-Z. Gong Short Review primary anilines undergo the asymmetric 1,2-hydroamination of aldehydes to give homoallylic alcohols, is initially tion reaction with a diverse spectrum of aryl/alkyldisubsti- generated from the arylborylation of a 1,3-diene with an tuted dienes as well as sterically differentiated alkyl/alkyl- aryldiazonium tetrafluoroborates and B2(Pin)2 rendered by disubstituted dienes, generating allylic amines 33 bearing the palladium and chiral anion phase-transfer combined various α-alkyl substituents in up to 78% yield, with >98:2 catalysis. rr, and 97% ee. Pd(OAc)2/CPA HO O NaHCO3, toluene Ar + Ar N2X + HR' Ph Ph R' R Ph O O Ph 3 Boration R BB 38 Ph O O Ph up to 99% yield Ph Ph >20:1 Z/E, 94% ee The boration of 1,3-dienes has received a great deal of iPr iPr

Ph Ph i attention because it generates a diverse range of alkyl boro- Ph Ph Pr O O P nates, which are important intermediates and building O O O B OH 32 33 34 35 iPr blocks in synthetic organic chemistry. Fe, Cu or Ir - * Ar R Int-7 iPr catalyzed boration of 1,3-dienes has been investigated in- iPr tensively by several groups; however, the Pd(0)-catalyzed CPA variants are relatively rare. Scheme 24 Enantioselective alkynylboration with buta-1,3-dienes and alkynyl bromides 3.1 Hydroboration 3.2 Alkynylboration The preparation of allylic boronates 36 from a 1,4-hydroboration of 1,3-dienes was initially reported by Suzuki’s To extend the scope of the palladium and chiral anion 36 group in 1989. Under the catalysis of Pd(PPh3)4, the hyd- phase-transfer combined catalysis for the difunctionaliza- roboration of buta-1,3-diene, isoprene, myrcene or 2,3-di- tion of 1,3-dienes, Gong and co-workers established a mul- methylbuta-1,3-diene with catecholborane (1,3,2-benzodi- ticomponent carbonyl allylation reaction of buta-1,3- oxaborole) 35 proceeds smoothly to provide 2-[(Z)-2-alkyl- dienes, alkynyl bromides, and aldehydes with octaphenyl- 2-butenyl]-1,3,2-benzodioxaboroles 36a–d with very high 2,2′-bi(1,3,2-dioxaborolane) (Scheme 25).38 The alkynyl regio- and stereoselectivity, which are able to undergo car- palladium phosphate Int-8 generated in situ from the me- bonyl allylation with benzaldehyde to produce homoallylic tathesis reaction of a chiral silver phosphate and the alcohols 37 in high yields and diastereoselectivities alkynyl palladium bromide turns out to be a key intermedi- (Scheme 23). ate that controls the stereoselectivity of chiral allylboronate intermediate Int-9. O HB O R R' R' OH R R' PhCHO Br Pd(OAc)2/CPAAg 35 O Ph O Ag2CO3, toluene R'' Pd(PPh ) (1.5 mol%) B + + 3 4 R' OH Ph Ph R' benzene O H R'' O O R Ph Ph 36a–d 37 R' BB 34a: R = H, R' = H Ph O O Ph up to 93% ee R 34b: R = H, R' = Me Ph Ph 34c: R = H, R' = CH2CH2CH=CC(Me)2 34d: R = Me, R' = Me' Ar Ph Ph Scheme 23 Hydroborations of 1,3-dienes CPA* Ph Ph O O L Pd n O O P O Ag B R O R * R' 3.2 Arylboration Int-8 Ar Int-9 Ar = 2,4,6-(Cy)3C6H2 CPAAg Recently, Gong and co-workers reported a stereo- and regioselective multicomponent carbonyl allylation reaction Scheme 25 Enantioselective alkynylboration with buta-1,3-dienes and of buta-1,3-dienes, aryldiazonium tetrafluoroborates, and alkynyl bromides aldehydes in the presence of octaphenyl-2,2′-bi(1,3,2-dioxaborolane) [B2(Pin)2], enabled by the combined catalysis of 4 Carbonation palladium acetate and chiral anion phase transfer, favoring the assembly of chiral Z-configured homoallylic alcohols 38 In addition to heteroatom nucleophiles, stabilized car- – – – in high yields and with excellent levels of enantioselectivity banions such as CH(CN)2, CH(CN)CO2R or CH(CO2R)2 have (Scheme 24).37 The key chiral allylboronate intermediate been widely employed in the Pd-catalyzed carbonation of Int-7, which then undergoes the asymmetric allylboryla- 1,3-dienes.

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 129

Syn thesis X. Wu, L.-Z. Gong Short Review

4.1 Vinyl or Arylation/Alkylation cessed by this reaction and was used as a chiral building block for the first catalytic asymmetric total synthesis of In 1983, Dieck and co-workers reported the first vinylal- (–)-∆9(12)-capnellene. Interestingly, the addition of sodium kylation reaction of 1,3-dienes with dimethyl sodio- bromide improved the enantioselectivity without erosion malonate and 1-bromo-2-methylpropene catalyzed by pal- of the chemical yield in all cases by preventing counteran- ladium complex formed from Pd(OAc)2 and PPh3, to give the ion exchange between the triflate anion and the enolate an- corresponding 1,4-selective product 39, albeit in moderate ion by coordination with sodium enolate. yield (Scheme 26).9 OTf

Pd(OAc) (1 mol%) 2 EtO C CO2Et PPh (2 mol%) 2 3 [Pd(allyl)Cl]2 (2.5 mol%) ++NaCH(CO2Me)2 H CH(CO2Me)2 (S)-BINAP (6.3 mol%) OTBDPS Br DMF + 135–140 °C, 4 h 39 NaBr, DMSO, r.t. 22% yield Na TBDPSO CO2Et Scheme 26 Vinylalkylation with 1-bromo-2-methylpropene CO2Et 43 87% ee, 77% yield

H H In 1987, Takahashi and co-workers described a Pd-catalyzed three-component arylalkylation of buta-1,3-diene H with aryliodide and malononitrile or methyl cyanoacetate, (–)-capnellene allowing for the generation of the corresponding 1,4-prod- Scheme 29 Enantioselective intramolecular arylalkylation for the total ucts 40 and 41 with iodobenzene and buta-1,3-diene in synthesis of (–)-∆9(12)-capnellene moderate yields (Scheme 27).39 4.3 Arylation/Intramolecular Alkylation

CH2(CN)2 Ph Pd(PPh3)2Cl2 (1 mol%) CN NaH, THF, 70 °C, 67 h CN In parallel with the development of heteroannulation of I 10 40 1,3-dienes, Larock and co-workers also accomplished an + 62% yield intramolecular carboannulation of 1,3-dienes with aryl io- CH2(CN)CO2Me Ph Pd(PPh3)2Cl2 (1 mol%) dides to give indanes 44 and tetralins 45 in high yields CO2Me NaH, THF, 70 °C, 45 h CN (Scheme 30).41 In addition to malonate-type nucleophiles, 41 42% yield other carbon nucleophiles α to an ester, a ketone or a ni- trone functionality were also tolerated, as exemplified by Scheme 27 Arylalkylation with iodobenzene 46–48, to afford the corresponding products in good yields. Nevertheless, a palladium-catalyzed annulation of 1,4- 4.2 Intramolecular Arylation or Vinylation/Alkyla- dienes using ortho-functionally substituted aryl halides tion was also developed by the same group.42

Pd(OAc)2 (5 mol%) CO Et Grigg and co-workers demonstrated that the sodio- 2 PPh3 (5 mol%) EtO C 2 CO2Et Na2CO3, n-Bu4NCl malononitrile could attack the π-allyl-palladium species, CO2Et + DMF, 60 °C, 8 d which is catalytically generated from an intramolecular 5- I 44 exo-trig cyclization on a proximate diene mediated with Pd 82% yield complex, to afford the corresponding regiospecific 1,4- Pd(OAc)2 (5 mol%) PPh3 (5 mol%) CO2Et 13 CO2Et Na CO , n-Bu NCl product 42 in 60% yield (Scheme 28). 2 3 4 CO2Et + CO2Et DMF, 60 °C, 12 d I CN 45 P(OAc)2 (5 mol%) NC 92% yield I PPh3 (10 mol%) + NaCH(CN)2 O N O MeCN, 80 °C NO2 Bn N CO2Et Bn O I 42 I I 60% yield 46 47 48 Scheme 28 Intramolecular arylalkylation Scheme 30 Arylation/intramolecular alkylation for the synthesis of in- dane and tetralin By using BINAP as a chiral ligand, Shibasaki established an intramolecular asymmetric Heck insertion and allylic al- The enantioselective carboannulation of 1,3-dienes and kylation cascade reaction (Scheme 29).40 An optically active aryl iodides was very recently established by Gong and co- functionalized bicyclo[3.3.0]octane 43 could be feasibly ac- workers. The use of chiral palladium complex of BINOL-

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 130

Syn thesis X. Wu, L.-Z. Gong Short Review based phosphoramidite ligand L9 allowed the reaction to Pd2(dba)3•CHCl3 (3 mol%) 2 4 L10 (7 mol%) 1 (HO) B provide optically active indanes 49 in high yields and with R ++1 3 2 OTf R2 excellent enantiomeric excesses (Scheme 31).43 Na2CO3, DMF, 45 °C, 16 h

R2 1 1 R 4 CO2R' Pd(OAc) (5 mol%) R 1 2 R'O2C + 1 4 + L9 (10 mol%) CO2R' R 1 2 4 R2 R CO2R' + Ar 1 R DIPEA, DME R I 60 °C, 72 h Ar 51 52 53 4,1-addition 1,2-addition 1,4-addition O2N 49 Ar up to 98% yield up to >99% ee F3C

O O P N N O N

L9 Ar = 3,5-(CF3)2C6H3 L10

Scheme 31 Enantioselective carboannulation of 1,3-dienes and aryl Scheme 33 Three-component coupling of isoprene, an alkenyl triflate, iodides by using a BINOL-based phosphoramidite ligand and styrenylboronic acid for the synthesis of skipped polyenes

4.4 Three-Component Arylation, Vinylation or Al- tion (for the generation of 53) can be achieved by using eas- kylation ily accessible pyrox ligand L10. Subsequently, Sigman and co-workers reported an in- In 2011, Sigman and co-workers reported a three-com- termolecular 1,2-diarylation reaction of 1,3-dienes with ponent coupling reaction of vinyl triflates and boronic acids aryldiazonium salts and aryl boronic acids, allowing the in- with terminal 1,3-dienes catalyzed by palladium to give stallation of two different aryl groups (Scheme 34).47 In the 1,2-vinylarylation product 50 (Scheme 32).44 The Pd-π-allyl presence of a chiral bicyclo[2.2.2]octadiene ligand L11, a intermediate int-10 tends to undergoing transmetalation good enantiomeric excess was obtained, albeit in rather low with a boronic acid derivative rather than β-hydride elimi- yield. nation, after reductive elimination to give the products 50.

i Pd2(dba)3 (5 mol%) Ph Pr H 1 L11 (12 mol%) R Ph 2 R Pd2(dba)3, KF Ar R2 Ph-N2BF4, Ph-B(OH)2 Ph OH + ArB(OH)2 R3 R3 Ph 10% yield DMA, 55 °C, 12 h 1 t TfO R NaHCO3, AmylOH 83% ee L11 50 –8 °C, 12 h

2 Ar R2 R Scheme 34 Asymmetric 1,2-diarylation 3 3 R 0 R R1 Pd Ln TfO 50 reductive oxidative elimination addition In 2015, Gong and co-workers successfully established a R3 R2 L Pd Ar n R3 highly enantioselective three-component coupling of 1,3- LnPd R1 R2 OTf dienes with aryl iodines and stabilized carbon nucleophiles 1 R (sodium dialkyl malonates) (Scheme 35).48 A H -BINOL- Heck 8 insertion ArB(OH)2 based phosphoramidite L12 turned out to be the most ef- 3 transmetallation R R3 TfO PdLn fective chiral ligand, which not only provides high catalytic Ln Pd OTf R1 R2 activity, but is also able to efficiently control the regio- and R1 R2 Int-10 stereoselectivity. Scheme 32 Three-component vinylarylation O2N Ar

Pd(OAc)2 (5 mol%) RO2C CO2R Ar1 O In 2015, the same group reported a three-component + L12 (10 mol%) P N Ar2 O 2 1 coupling of isoprene, an alkenyl triflate, and styrenylboron- Ar -I MTBE, 80 °C, 72 h Ar + ic acid to produce skipped polyenes from simple chemical up to 93% yield Ar NaCH(CO2R)2 up to 98% ee 45,46 feedstocks (Scheme 33). However, complex isomeric Ar = 3,5-(CF3)2C6H3 L12 product mixtures 51–53 were always obtained because of the difficult-to-control migratory insertion of isoprene into Scheme 35 Enantioselective three-component coupling of 1,3-dienes a Pd-alkenyl bond, while a good site selectivity of 1,4-addi- with aryl iodines and sodium dialkyl malonates

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 131

Syn thesis X. Wu, L.-Z. Gong Short Review

4.5 Others 1 R Pd(OAc)2 (5 mol%) P(2-furyl)3 (6 mol%) I 1 R' K2CO3 R Yoshida and Ihara reported a cascade insertion–ring ex- + R' R2 pansion reaction of 1,3-dienylcyclobutanols with aryl io- R2 MeCN, 90 °C, 18 h O dides to generate (Z)-2-(3-aryl-1-propenyl)cyclopenta- OH nones 54 in a stereospecific manner (Scheme 36).49 In the 55 reaction, an arylpalladium complex formed from aryl io- Ph dide with palladium(0) undergoes a Heck insertion reaction Pd(0) I with 1,3-dienyl moiety to give an allylic palladium interme- allylative dearomatization diate Int-11. The Int-11 reacts with a base to form a zwitte- (P6) O Ln I rionic π-allylpalladium intermediate Int-12, which subse- Pd OH quently undergoes a ring rearrangement to furnish a ring- oxidative Ph addition expanded product 54 and regenerate the palladium(0) cata- (P4) I lyst. Pd Ln O H Pd2(dba)3•CHCl3 (5 mol%) O P(o-tol)3 (20 mol%) H B OH Ln I Ag2CO3, toluene Pd OH + ArI 45 °C, 2–13 h R2 Ph Ph 2 R1 Ar R1 R 54 olefin insertion up to 98% yield (P5)

O Pd(0) OH H ArI Scheme 37 Dearomatization reaction of phenol-derived biaryls with

R2 1,3-dienes for the synthesis of spirocyclic compounds R1 Ar I Ar 54 Pd ArPdI Pd+ O– OH I Ar Pd2(dba)2 (2.5 mol%) L5 (6 mol%) Pd I * Ph K2CO3 * 1 R2 1 R2 R R + Ph Int-12 OH R2 R2 DME, 65 °C, 18 h AgI 1 O / H O, CO 2 OH 2 2 2 R1 R 1 /2 Ag2CO3 Int-11 Ph Ph Ph Scheme 36 Cascade insertion-ring expansion reaction of 1,3-dienylcy- O P N clobutanols with aryl iodides for the synthesis of (Z)-2-(3-aryl-1-prope- O nyl)cyclopentanones Ph O O ent-L5 33% yield 76% yield 70% ee 80% ee Recently, Luan and co-workers described a Pd-catalyzed 2.5:1 dr dearomatization reaction of phenol-derived biaryls with Scheme 38 Preliminary studies on asymmetric reaction 1,3-dienes to generate spirocyclic compounds 55 in good yields and with excellent chemo- and regioselectivity [Pd4]BF4 or [Pd5]BF4 50 (5 mol%) (Scheme 37). The reaction proceeds through a reaction se- 2 2 2 R EWG Et3N R EWG1 R1 + R1 quence of oxidative addition (P4, Scheme 38) to the C–I 1 CH Cl , 22 °C, 2–20 h EWG 2 2 1 bond, regioselective olefin insertion (P5), and allylative EWG 56 dearomatization (P6). up to 96% yield up to 97.5:2.5 er Preliminary studies on the enantioselective version re- O vealed that chiral phosphoramidite ligand ent-L5 could al- N PAr2 Pd low the reaction to yield spirocyclic compounds with good tBu BF4 50 enantioselectivities (Scheme 38). [Pd4]BF4 Ar = 3,5-(CF3)2C6H3 In a continuation of the asymmetric hydroamination of [Pd5]BF4 Ar = 4-CF3C6H4 30,31 1,3-dienes, Malcolmson and co-workers recently de- Scheme 39 Enantioselective hydroalkylation scribed a highly efficient and enantioselective intermolecular addition of activated C-pronucleophiles to acyclic 1,3- 51 dienes enabled by Pd catalysts ([Pd4]BF4 or [Pd5]BF4) bearing electronically deficient phosphines (Scheme 39). The 1,2-difunctionalized products 56 could be obtained in up to 96% yield and 95% ee.

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 132

Syn thesis X. Wu, L.-Z. Gong Short Review

5 Hydrogenation groups such as aldehydes and ketones generally give higher yields. Particularly, o-iodobenzyl alcohol can be employed Sigman and co-workers recently reported the only ex- to form isochroman derivative 62 (Scheme 41, eq. 4). ample to date of regio- and stereoselective 1,2-vinylhydro- Recently, Han and co-workers realized an asymmetric genation of terminal 1,3-dienes with enol triflates/nonaf- version of the Pd-catalyzed difunctionalization between o- lates in the presence of sodium formate (Scheme 40).52 iodobenzyl alcohol and arylbutadienes (Scheme 42).11 Un- Trapping of the π-allyl intermediate generated from the ini- der similar conditions in the synthesis of chiral indolines,11 tial migratory insertion of the diene with a hydride source chiral isochromans 63a–d could be obtained with high en- allows access to structurally complex and synthetically antioselectivities and moderate yields. challenging stereodefined (E)- and (Z)-tri- and tetrasubsti- Pd(OAc)2 (5 mol%) tuted alkene building blocks 57. OH L1 (15 mol%) Ar + Ar I KHCO3, DME, 80 °C O 1 Pd2(dba)3•CHCl3 1 R H R 61 63 HCO2Na + R2 R2 Ar X Ar DMA, r.t., N2, 16 h F R3 R3 X = OTf or ONf 57 up to 86% yield O O

Scheme 40 1,2-Vinylhydrogenation of (E)- and (Z)-tri- and tetrasubsti- 63a 63b tuted alkene 36% yield, 80% ee 50% yield, 79% ee OMe 6 Oxygenation O O

63c 63d 46% yield, 80% ee 76% yield, 71% ee Larock and co-workers created a Pd-catalyzed oxyannu- Scheme 42 Enantioselective arylation/intramolecular oxygenation to lation of 1,3-dienes with o-iodophenol substrates to give di- generate chiral isochromans hydrobenzofuran 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 In 2005, Yeh and co-workers reported a palladium-cata- the corresponding dihydrobenzofurans 58–60 in moderate lyzed difunctionalization of 7-hydroxy-1,3-dienes with aryl yields (Scheme 41, eqs. 1–3). The reaction of o-iodophenol bromides (Scheme 43).53 The reaction proceeded through and isoprene affords compound 60 in reasonable yield different paths depending on the structure of the sub- (Scheme 41, eq. 3), although a minor amount of a regioiso- strates. With cyclic 7-hydroxy-1,3-dienes 64, the insertion mer is observed. Phenols bearing electron-withdrawing 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

Pd(dba)2 (5 mol%) n O H OH Na2CO3, Bu4NCl + (1) Ar Pd(PPh3)4 (2 mol%) Ar I DMF, 100 °C, 1 d H ( )n dpe-phos (2 mol%) 58 ++ArBr O 44% O OH tBuONa, THF Pd(OAc)2 (5 mol%) ° n O 65 C, 2 h OH NaOAc, Bu4NCl 64 n = 1 66 n = 1 67 n = 0 + C4H9 (2) C H 65 n = 0 I DMF, 100 °C, 1 d 4 9 59 Ar Ln 75% Ar Ar PdLn Pd PdLn Ar Pd(OAc)2 (5 mol%) OH n O O O Na2CO3, Bu4NCl O O O + + (3) I DMF, 100 °C, 1 d 60 ( )n LnPd(Ar)Br Int-13 7:1 60' n = 1 Int-15 51% yield 66 OH NaOtBu Ar Ar Ar Ar Pd(OAc)2 (5 mol%) PdLn PPh3 (5 mol%) 64 n = 1 Pd n 65 n = 0 Ln or PdLn OH KOAc, Bu4NCl O O (4) O + C4H9 O O I DMF, 80 °C, 1 d C4H9 62 61 Int-14 E/Z = 16:1 Int-16 Int-16' 67 56% yield n = 0 Scheme 41 Arylation/intramolecular oxygenation to generate dihy- Scheme 43 Difunctionalization of 7-hydroxy-1,3-dienes with aryl bro- drobenzofuran and isochroman derivatives mides

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 133

Syn thesis X. Wu, L.-Z. Gong Short Review

65 proceeded through the insertion of the double bond into 8 Conclusion and Outlook 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 In the past forty years, the palladium(0)-catalyzed di- after reductive elimination. The difference in the formation functionalization reactions of 1,3-dienes have made signifi- of alkoxyarylation products (1,4- vs. 1,2-alkoxyarylation) cant progress, culminating in a diverse range of transforma- between cyclic and acyclic substrates actually arises be- tions that provide efficient way to assemble densely func- cause the η1-η3-η1 allylic isomerization may be faster in the tionalized molecules from readily available substances. cyclic intermediate Int-15 than the acyclic intermediate Abundant availability of chiral ligands for the palladium(0) Int-16 or Int-16′ for steric reasons. catalysis has enabled switching the racemic reaction to an To synthesize capnellenol, a catalytic asymmetric cas- enantioselective version. Nevertheless, the stereochemical cade Heck reaction and allylic esterification was accom- control remains a formidable challenge in the difunctional- plished by Shibasaki.14,54 Various ligands and solvents were ization of 1,3-dienes, as indicated by the fact that many re- screened to reveal that the chiral palladium complex of (S)- actions are still not enantioselective. In addition, 1,3-diene BINAP delivered the best results in dimethyl sulfoxide (DM- components in these known processes are limited to aryl SO) (Scheme 44). substituted or terminal dienes. Either alkyl substituted or internal acyclic dienes have rarely been reaction compo-

Pd(OAc)2 (1.7 mol%) OAc nents in the asymmetric difunctionalization. Moreover, ef- OTf (S)-BINAP (2.1 mol%) H n Bu4NOAc ficient control of regioselectivity is another big deal in such

DMSO, 20 °C, 2.5 h transformations. Therefore, new concepts, proper chiral ligands designed for Pd catalysis, and the development of 80% ee 89% yield new transformations for building up structural complexity Scheme 44 Enantioselective intramolecular vinyloxygenation will be future focuses in the difunctionalization of 1,3- dienes. 7 Silylation Funding Information

Optically active allylsilanes are useful reagents in stereo- We are grateful for financial support from NSFC (21672197, selective organic synthesis, because they are able to partici- 21672049).Nationa lNatura lScience Foundation o fChina (21672197)Nationa lNatura lScience Foundation o fChina (2167204) pate in asymmetric carbonyl or imine allylations with highly efficient chirality transfer.55 Increasing attention has References been directed toward their asymmetric catalytic synthesis. Among the methods to access chiral allylsilanes, the palla- (1) (a) Morrow, N. L. Environ. Health Perspect. 1990, 86, 7. dium-catalyzed asymmetric hydrosilylation of 1,3-dienes (b) White, W. C. Chem.-Biol. Interact. 2007, 166, 10. has unique advantages, for example, using readily accessi- (2) (a) De Paolis, M.; Chataigner, I.; Maddaluno, J. Top. Curr. Chem. ble starting materials.5 However, no breakthrough had been 2012, 327, 87. (b) Olivares, A. M.; Weix, D. J. J. Am. Chem. Soc. achieved in this field until recently.56 The chiral monoden- 2018, 140, 2446. (c) Nguyen, V. T.; Dang, H. T.; Pham, H. H.; Nguyen, V. D.; Flores-Hansen, C.; Arman, H. D.; Larionov, O. V. tate phosphine L13 with a binaphthyl moiety was identi- J. Am. Chem. Soc. 2018, 140, 8434. (d) Hu, T.-J.; Li, M.-Y.; Zhao, fied as the most efficient ligand for the asymmetric hydro- Q.; Feng, C.-G.; Lin, G.-Q. Angew. Chem. Int. Ed. 2018, 57, 5871. silylation of cyclic 1,3-dienes whereas the planar chiral fer- (e) Fiorito, D.; Folliet, S.; Liu, Y.; Mazet, C. ACS Catal. 2018, 8, rocenylmonophosphine L14 with two ferrocenyl moieties 1392. (f) Al-Jawaheri, Y.; Turner, M.; Kimber, M. C. Synthesis turned out to be an efficient ligand for the reaction involv- 2018, 50, 2329. (g) Matsumoto, K.; Mizushina, N.; Yoshida, M.; ing linear 1,3-dienes (Scheme 45).5 Shindo, M. Synlett 2017, 28, 2340. (h) Schmidt, B.; Audoersch, S.; Kunz, O. Synthesis 2016, 48, 4509. (3) (a) Eschenbrenner-Lux, V.; Kumar, K.; Waldmann, H. Angew. * SiCl3 Chem. Int. Ed. 2014, 53, 11146. (b) Sherburn, M.; Mackay, E. Syn- ( )n HSiCl ( )n 3 thesis 2014, 47, 1. R Pd/L* R * (4) (a) Sigman, M. S.; Werner, E. W. Acc. Chem. Res. 2012, 45, 874.

SiCl3 (b) Jensen, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083. (c) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111, MeO 2981. (d) Schultz, D. M.; Wolfe, J. P. Synthesis 2012, 44, 351. Ar Ph2P P (e) Xiong, Y.; Sun, Y.; Zhang, G. Tetrahedron Lett. 2018, 59, 347. L* = OMe Fe OMe Fe (f) Wu, Z.; Zhang, W. Chin. J. Org. Chem. 2017, 37, 2250. (5) Han, J. W.; Hayashi, T. Tetrahedron: Asymmetry 2010, 21, 2193. (6) Patel, B. A.; Dickerson, J. E.; Heck, R. F. J. Org. Chem. 1978, 43, L13 L14 5018. Scheme 45 Asymmetric hydrosilylation of 1,3-dienes (7) Patel, B. A.; Kao, L. C.; Cortese, N. A.; Minkiewicz, J. V.; Heck, R. F. J. Org. Chem. 1979, 44, 918.

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134 134

Syn thesis X. Wu, L.-Z. Gong Short Review

(8) (a) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) Stakem, F. G.; (33) Wu, J. Y.; Moreau, B.; Ritter, T. J. Am. Chem. Soc. 2009, 131, Heck, R. F. J. Org. Chem. 1980, 45, 3584. 12915. (9) Oconnor, J. M.; Stallman, B. J.; Clark, W. G.; Shu, A. Y. L.; Spada, R. (34) (a) Sasaki, Y.; Zhong, C.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. E.; Stevenson, T. M.; Dieck, H. A. J. Org. Chem. 1983, 48, 807. 2010, 132, 1226. (b) Semba, K.; Shinomiya, M.; Fujihara, T.; (10) Larock, R. C.; Berriospena, N.; Narayanan, K. J. Org. Chem. 1990, Terao, J.; Tsuji, Y. Chem. Eur. J. 2013, 19, 7125. (c) Li, X.; Meng, F.; 55, 3447. Torker, S.; Shi, Y.; Hoveyda, A. H. Angew. Chem. Int. Ed. 2016, 55, (11) Chen, S.-S.; Meng, J.; Li, Y.-H.; Han, Z.-Y. J. Org. Chem. 2016, 81, 9997. (d) Jiang, L.; Cao, P.; Wang, M.; Chen, B.; Wang, B.; Liao, J. 9402. Angew. Chem. Int. Ed. 2016, 55, 13854. (e) Sardini, S. R.; Brown, (12) Flubacher, D.; Helmchen, G. Tetrahedron Lett. 1999, 40, 3867. M. K. J. Am. Chem. Soc. 2017, 139, 9823. (f) Smith, K. B.; Huang, (13) Grigg, R.; Sridharan, V.; Sukirthalingam, S.; Worakun, T. Tetra- Y.; Brown, M. K. Angew. Chem. Int. Ed. 2018, 57, 6146. hedron Lett. 1989, 30, 1139. (35) Fiorito, D.; Mazet, C. ACS Catal. 2018, 8, 9382. (14) Kagechika, K.; Ohshima, T.; Shibasaki, M. Tetrahedron 1993, 49, (36) Satoh, M.; Nomoto, Y.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1773. 1989, 30, 3789. (15) (a) Overman, L. E.; Rosen, M. D. Angew. Chem. Int. Ed. 2000, 39, (37) Tao, Z.-L.; Adili, A.; Shen, H.-C.; Han, Z.-Y.; Gong, L.-Z. Angew. 4596. (b) Overman, L. E.; Rosen, M. D. Tetrahedron 2010, 66, Chem. Int. Ed. 2016, 55, 4322. 6514. (38) (a) Shen, H.-C.; Wang, P.-S.; Tao, Z.-L.; Han, Z.-Y.; Gong, L.-Z. Adv. (16) (a) Qin, G.; Li, L.; Li, J.; Huang, H. J. Am. Chem. Soc. 2015, 137, Synth. Catal. 2017, 359, 2383. (b) Zhang, Z.-J.; Tao, Z.-L.; Arafate, 12490. (b) Zhang, G.; Gao, B.; Huang, H. Angew. Chem. Int. Ed. A.; Gong, L.-Z. Acta Chim. Sinica 2017, 75, 1196. 2015, 54, 7657. (c) Xie, Y.; Hu, J.; Xie, P.; Qian, B.; Huang, H. (39) (a) Uno, M.; Takahashi, T.; Takahashi, S. J. Chem. Soc., Chem. J. Am. Chem. Soc. 2013, 135, 18327. (d) Xie, Y.; Hu, J.; Wang, Y.; Commun. 1987, 785. (b) Uno, M.; Takahashi, T.; Takahashi, S. Xia, C.; Huang, H. J. Am. Chem. Soc. 2012, 134, 20613. J. Chem. Soc., Perkin Trans. 1 1990, 647. (17) Liu, Y.; Xie, Y.; Wang, H.; Huang, H. J. Am. Chem. Soc. 2016, 138, (40) Ohshima, T.; Kagechika, K.; Adachi, M.; Sodeoka, M.; Shibasaki, 4314. M. J. Am. Chem. Soc. 1996, 118, 7108. (18) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem. Int. Ed. 1998, (41) Larock, R. C.; Fried, C. A. J. Am. Chem. Soc. 1990, 112, 5882. 37, 2580. (42) Larock, R. C.; Berriospena, N. G.; Fried, C. A.; Yum, E. K.; Tu, C.; (19) Bar, G. L.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Leong, W. J. Org. Chem. 1993, 58, 4509. Soc. 2005, 127, 7308. (43) Wu, X.; Chen, S. S.; Zhang, L.; Wang, H. J.; Gong, L. Z. Chem. (20) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. Commun. 2018, 9595. (21) Zhu, Y.; Cornwall, R. G.; Du, H.; Zhao, B.; Shi, Y. Acc. Chem. Res. (44) Liao, L.; Jana, R.; Urkalan, K. B.; Sigman, M. S. J. Am. Chem. Soc. 2014, 47, 3665. 2011, 133, 5784. (22) Zhao, B.; Du, H.; Cui, S.; Shi, Y. J. Am. Chem. Soc. 2010, 132, 3523. (45) McCammant, M. S.; Sigman, M. S. Chem. Sci. 2015, 6, 1355. (23) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, (46) Xu, L.; Zhang, X.; McCammant, M. S.; Sigman, M. S.; Wu, Y.-D.; 11688. Wiest, O. J. Org. Chem. 2016, 81, 7604. (24) Xu, L.; Du, H.; Shi, Y. J. Org. Chem. 2007, 72, 7038. (47) Stokes, B. J.; Liao, L.; de Andrade, A. M.; Wang, Q.; Sigman, M. S. (25) Xu, L.; Shi, Y. J. Org. Chem. 2008, 73, 749. Org. Lett. 2014, 16, 4666. (26) (a) Reznichenko, A. L.; Nawara-Hultzsch, A. J.; Hultzsch, K. C. (48) Wu, X.; Lin, H. C.; Li, M. L.; Li, L. L.; Han, Z. Y.; Gong, L. Z. J. Am. Top. Curr. Chem. 2014, 343, 191. (b) Huang, L.; Arndt, M.; Chem. Soc. 2015, 137, 13476. Goossen, K.; Heydt, H.; Goossen, L. J. Chem. Rev. 2015, 115, 259. (49) Yoshida, M.; Sugimoto, K.; Hara, M. Org. Lett. 2004, 6, 1979. (c) Coman, S. M.; Parvulescu, V. I. Org. Process Res. Dev. 2015, 19, (50) Luo, L.; Zheng, H.; Liu, J.; Wang, H.; Wang, Y.; Luan, X. Org. Lett. 1327. 2016, 18, 2082. (27) (a) Löber, O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. (51) Adamson, N. J.; Wilbur, K. C. E.; Malcolmson, S. J. J. Am. Chem. 2001, 123, 4366. (b) Johns, A. M.; Utsunomiya, M.; Incarvito, C. Soc. 2018, 140, 2761. D.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 1828. (52) Saini, V.; O’Dair, M.; Sigman, M. S. J. Am. Chem. Soc. 2015, 137, (28) Minami, T.; Okamoto, H.; Ikeda, S.; Tanaka, R.; Ozawa, F.; 608. Yoshifuji, M. Angew. Chem. Int. Ed. 2001, 40, 4501. (53) Yeh, M. C. P.; Tsao, W. C.; Tu, L. H. Organometallics 2005, 24, (29) Banerjee, D.; Junge, K.; Beller, M. Org. Chem. Front. 2014, 1, 368. 5909. (30) Adamson, N. J.; Hull, E.; Malcolmson, S. J. J. Am. Chem. Soc. 2017, (54) Kagechika, K.; Shibasaki, M. J. Org. Chem. 1991, 56, 4093. 139, 7180. (55) Wang, P.-S.; Shen, M.-L.; Gong, L.-Z. Synthesis 2017, 50, 956. (31) Park, S.; Malcolmson, S. J. ACS Catal. 2018, 8, 8468. (56) (a) Park, H. S.; Han, J. W.; Shintani, R.; Hayashi, T. Tetrahedron: (32) (a) Shimizu, Y.; Kanai, M. Tetrahedron Lett. 2014, 55, 3727. Asymmetry 2013, 24, 418. (b) Park, H.-S.; Shin, H. M.; Namgung, (b) Lazreg, F.; Nahra, F.; Cazin, C. S. J. Coord. Chem. Rev. 2015, S.; Han, J. W. Bull. Korean Chem. Soc. 2014, 35, 2613. 293-294, 48. (c) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Tetra- hedron 2015, 71, 2183. (d) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A.; Westcott, S. A.; Marder, T. B. Chem. Rev. 2016, 116, 9091.

Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, 122–134