Chemodivergent and Diastereoselective Synthesis of γ-Lactones and

Subscriber access provided by Université de Strasbourg - Service Commun de la Documentation

Communication

Chemodivergent and Diastereoselective Synthesis of #-Lactones and #Lactams: A Heterogeneous Palladium-Catalyzed Oxidative Tandem Process Man-Bo Li, A. Ken Inge, Daniels Posevins, Karl P. J. Gustafson, Youai Qiu, and Jan-E. Bäckvall J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b09562 • Publication Date (Web): 25 Oct 2018 Downloaded from http://pubs.acs.org on October 25, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Chemodivergent and Diastereoselective Synthesis of γ-Lactones and γ-Lactams: A Heterogeneous Palladium-Catalyzed Oxidative Tandem Process Man-Bo Li,† A. Ken Inge,‡ Daniels Posevins,† Karl P. J. Gustafson,† Youai Qiu,*,† and Jan-E. Bäckvall*,† †Department

of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden ‡Department

Supporting Information ABSTRACT: A palladium-catalyzed oxidative tandem process of enallenols was accomplished within a homogeneous/heterogeneous catalysis manifold, setting the stage for highly chemodivergent and diastereoselective synthesis of γ-lactones and γ-lactams under mild conditions.

γ-Lactones and γ-lactams are core structures of a large variety of natural and bioactive compounds, as well as versatile intermediates in the synthesis of complex molecules and recyclable polymers.1 As a result, many studies have been directed toward the selective construction of this structural unit.2 In most cases, γ-lactones and γ-lactams are fused with other cyclic units to form bicyclic or polycyclic structures with several chiral centers (Figure 1).1-3 Notable progress was obtained in the past decade.2,3 Despite these major advances, the procedures reported typically require multistep synthesis with unsatisfactory atom- and step-economy.1a-d,2a-e,3 Thus, economical and efficient access to ring fused γ-lactones and γ-lactams with high regio- and diastereoselectivity is still of high demand. Figure 1. Representative bioactive compounds O

O

O

OH

O

O

O O

strigol isolated from cotton

O

OH

O

O

O

O

O

O

orobanchol isolated from red clover roots

O

GR24 synthetic analogue of strigol

recent interest in Pd(II)-catalyzed oxidative carbocyclization of allenes for construction of synthetically important carbocyclic skeletons,5 we have now designed an oxidative tandem route to ring fused γ-lactones (Scheme 1). We envisioned that Int-A would be generated from the palladium complex of 1 via allene attack on Pd(II). In the presence of carbon monoxide (CO), insertion of CO into the Pd–C bond of Int-A would produce Int-B, which could undergo an insertion of the olefin to form Int-C. A subsequent CO insertion into the Pd–C bond of Int-C would produce Int-D, which would be trapped by the hydroxyl group to give cyclopentenone-fused γ-lactone 2 with two chiral centers. This bicyclic skeleton is a structural element of many natural and bioactive compounds (Figure 1).6 Some typical examples include the strigolactone family6a-e members: strigol,6a orobanchol6d and GR24,6e which are new plant hormones that attracted much attention recently. The envisioned tandem process for the construction of this valuable skeleton would undergo selective carbonylation-carbocyclization-carbonylation-lactonization which involves four-step bond formation including twice CO insertion with high atom- and step-economy. In addition, the hydroxyl group of enallenol 1 would potentially act as a directing group to control the diastereoselectivity of the tandem reaction. However, considering the possible side-reactions during each step (Scheme 1), the control of chemoselectivity during the tandem process would be highly challenging. Scheme 1. Proposed tandem approach for formation of cyclopentenone-fused γ-lactone skeleton OH

R

R

strigolactone family seed germination stimulant

* O

Pd(II)-catalyst, oxidant CO

O

O O O

O O

sinularone C isolated from soft coral Sinularia sp. antifouling activity

lactonization

allene attack

OH

O

2

1

OH

H

H

O

scrodentoid F isolated from scophularia dentata anti-inflammatory activity

HO

HO

CO insertion

R

O

didemnenone A isolated from trididemnum cyanophorum antimicrobial and antifungal activity

An efficient way to construct complicated molecular structures with high atom- and step-economy is to employ a multistep tandem process, in which a consecutive series of reactions occur via multiple bond formation and cyclization.4 Following our

olefin insertion

R

OH

R

*

Pd (II)

Pd (II)

* O Int-C

O Int-B

Int-A

OH

R

O

*

O

R

R

PdX

O A

ACS Paragon Plus Environment

OH

O

B

O C

(II) CO Pd insertion

R

(II) OH Pd

*

O

* O Int-D

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Our initial attempt of the Pd(II)-catalyzed oxidative tandem process began with the reaction of enallenol 1a in the presence of Pd(TFA)2 (TFA = trifluoroacetate) (5 mol%). To our delight, the cyclopentenone-fused γ-lactone 2a was obtained in 28% yield as a sole diastereomer (eq 1). Another γ-lactone product 3a was also formed in 65% yield due to the reaction of acyl palladium with the hydroxyl group (in Int-B, Scheme 1). OH n-Bu

+

Pd(TFA)2 (5 mol %)

CO 1 atm

BQ (1.1 equiv) DCE, rt, 12 h

1a

n-Bu

n-Bu

O

O +

O

(1)

O

O

3a, 65%

2a, 28%

With these inspiring results in hand, we turned to optimize the reaction conditions for the chemoselective formation of cyclopentenone-fused γ-lactone 2a. However, γ-lactone 3a was always the major product no matter how the homogeneous reaction conditions were changed (Table 1, entries 1-8, for more details, see Supporting Information, P. S7). We then turned our attention to the heterogeneous Pd catalyst comprising of palladium immobilized on amino-functionalized siliceous mesocellular foam (Pd-AmP-MCF), which is a new heterogeneous palladium catalyst developed by our group.7 It was used for catalytic hydrogenation of nitro compounds, alkenes and alkynes with H2, and exhibited excellent reactivity and selectivity compared to homogeneous and other heterogeneous Pd catalyst.7c-f Surprisingly, the non-reduced form, PdII-AmP-MCF, increased the yield of 2a to 68% and suppressed the yield of 3a to 20% (Table 1, entry 9). By changing the solvent from DCE to CH2Br2, oxidant from BQ to methyl-BQ, and the amount of PdII-AmP-MCF from 5 mol % to 2 mol %, 2a was obtained in 80% yield and with a 20:1 chemoselectivity (Table 1, entry 10, for more details, see Supporting Information, P. S8). Table 1. Optimization of the reaction conditions OH

n-Bu

n-Bu

Pd source (5 mol %) +

CO 1 atm

BQ (1.1 equiv) solvent, rt, 12 h

O

n-Bu O

O + O

O

1a

3a

2a

Entry

Pd source

Solvent DCE DCE DCE

Yield of 2a (%)a 28 17 12

Yield of 3a (%)a 65 50 44

1 2 3

Pd(TFA)2 Pd(OAc)2 Pd(PPh3)2Cl2

4

O O Ph S . S Ph Pd(OAc)2

DCE

17

35

5 Pd(TFA)2 DCM 28 67 6 Pd(TFA)2 CHCl3 20 70 7 Pd(TFA)2 CH2Br2 35 55 8 Pd(TFA)2 THF 26 52 9 PdII-AmP-MCF DCE 68 20 10b PdII-AmP-MCF CH2Br2 80 4 11c Pd(TFA)2 CH2Br2 15 57 12d Pd(TFA)2 CHCl3 3 86 aDetermined by NMR using anisole as the internal standard. b2 mol% of PdII-AmP-MCF and methyl-BQ was used. c15 bar of CO was used. d10 mol% of CH3CO2H was used. Despite the elegant work on ligand- and solvent-controlled chemoselective carbonylative reactions developed in homogeneous systems,8,9 up to now, there are no reports on catalyst-controlled chemo- and diastereoselective carbonylations achieved with heterogeneous palladium catalysts. As a result of its high surface area (500-800 m2g-1) and large pore sizes (~26 nm),

Page 2 of 6

amino-functionalized mesocellular foam (AmP-MCF) could act as ideal support for Pd and excellent host for CO gas.10 We assume that two factors may lead to the aggregation of CO in Pd-AmP-MCF to favor the formation of 2a (Figure 2). First, the physical adsorption of CO in the porous AmP-MCF would increase the concentration of CO in the reaction mixture. Control experiments showed that compared to Pd(TFA)2 or Pd(OAc)2, the Pd(TFA)2 + AmP-MCF or Pd(OAc)2 + AmP-MCF catalytic system improved the chemoselectivity of the reaction for formation of cyclopentenone-fused γ-lactone 2a (see Supporting Information, Table S1, entries 7, 10, and Table S2, entries 4, 5). In addition, an increase of the ratio of 2a:3a from 36:40 to 47:30 was observed with the gradual increase of the amount of AmP-MCF with Pd(OAc)2 as the catalyst (see Supporting Information, p. S8, Table S2, entries 5-7). Second, in the presence of CO, Pd(II) in the heterogeneous catalyst was partially reduced to Pd(0). We observed a mixture of Pd(0) and Pd(II) atoms accommodated in the Pd-AmP-MCF after reaction.11 The coexistence of Pd(0) and Pd(II) atoms in Pd-AmP-MCF was also detected in our very recent work by using Pd0-AmP-MCF in Pd-catalyzed carbocyclization, in which the Pd(II) was generataed from the oxidation of Pd(0) by BQ.7g The Pd(0) atoms in PdII-AmP-MCF can adsorb CO efficiently for the next carbonylative step (Figure 2). Control experiments showed that compared to Pd(II) salts, a Pd colloid improved the chemoselectivity of the reaction for formation of cyclopentenone-fused γ-lactone 2a (see Supporting Information, P. S8, Table S2, entries 11, 12).12 On the other hand, the use of Pd(TFA)2 or Li2PdCl4 (the precursor of PdII-AmP-MCF) as the catalyst did not lead to any increase of the chemoselectivity for formation of 2a with propylamine as the additive (see Supporting Information, Table S1, entry 7, and Table S2, entries 8-10). This observation suggests that coordination of amine to Pd in Pd-AmP-MCF is not causing the switch of the observed chemoselectivity. Based on these results, we propose that Pd-AmP-MCF adsorb CO efficiently to favor selective formation of 2a. To be noted, 2a was obtained only in 15% yield with Pd(TFA)2 as the catalyst in the presence of 15 bar of CO (Table 1, entry 11), demonstrating that the chemoselectivity of the reaction for the formation of 2a cannot be improved by simply increasing the CO pressure in the homogeneous catalytic system. Interestingly, chemoselective formation of γ-lactone 3a was achieved in 86% yield and with >20:1 chemoselectivity by using 10 mol % of CH3CO2H as the additive in the homogeneous catalytic system (Table 1, entry 12). Figure 2. Aggregation of CO in Pd-AmP-MCF for switching chemoselectivity CO NH2

H2 N

NH2

OH n-Bu

NH2 NH2 NH2 NH2 NH2

H2 N H2 N H2 N H2 N H2 N H2 N

n-Bu

Aggregation of CO in Pd-AmP-MCF

NH2 NH2 NH2 NH2 NH2 NH2 NH2

O O

H2 N H2 N H2 N H2 N H2 N H2 N H2 N

H2 N

OC

Pd-AmP-MCF CO

O

CO CO CO

Pd(II) atom

CO

Pd(0) atom

CO

Under the optimized reaction conditions, we investigated the scope for the chemo- and diastereoselective formation of cyclopentenone-fused γ-lactones 2 (Scheme 2). Enallenols 1a-1h with an aliphatic, aromatic or hydrogen substituent in the R1 position worked equally well to give cyclopentenone-fused γ-lactones 2a-2h in good yields. An ester as functional group was tolerated in the tandem reaction (2g). In addition to two methyl substituents, the substrates with cyclopentylidene and

ACS Paragon Plus Environment

Page 3 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society cyclooctylidene substituents on the allene moiety also worked well, affording the corresponding products 2i and 2j in good yields. Unsymmetrical enallenol 1k bearing phenyl and methyl groups afforded 2k in 77% yield. To our delight, enallenol 1l bearing a tertiary alcohol led to the corresponding product 2l with a quaternary carbon stereocenter in good yield, and enallenol 1m bearing methyl group in R4 position afforded the corresponding cyclopentenone-fused γ-lactone 2m as a sole diastereomer with three chiral centers in 52% yield. To be noted, all of the cyclopentenone-fused γ-lactones 2 were obtained as single diastereomers with high diastereoselectivity.13 Scheme 2. Scope for selective formation of 2 HO R2

R1

R

R3 R4

PdII-Amp-MCF (2 mol %) +

CO

recycling test

O

(2a) 79%, >50:1 d.r.

6th: 77%, >50:1 d.r.

3rd: 76%, >50:1 d.r.

7th: 76%, >50:1 d.r.

4th: 77%, >50:1 d.r.

8th: 75%, >50:1 d.r.

5th: 75%, >50:1 d.r.

9th: 75%, >50:1 d.r.

Ph

Me O

O

(2c) 80%, >50:1 d.r.

O O

(2d) 75%, >50:1 d.r.

CO2Et

(2e) 82%, >50:1 d.r. n-Bu

O

O

O

O

O

O

O O

O

(2b) 75%, >50:1 d.r.

Recyclable Recoverable Without leaching

O

O

O

O O (2g) 73%, >50:1 d.r.

O (2f) 70%, >50:1 d.r. n-Bu

(2h) 52%, >50:1 d.r.

n-Bu O

n-Bu O

O

O

Me

n-Bu O

O

O O

Ph O (2k) 77%, >50:1 d.r.

(2i) 78%, >50:1 d.r.

O

H

(2l) 78%, >50:1 d.r.

O O

Me

(R,S)-2a 82%, >99% ee

O

(R,S)-2b 72%, >99% ee

(R,S)-2d 76%, >99% ee n-Bu

O

O

O

O

O

O

(R,R)-2h 55%, >99% ee

(R,S)-2i 75%, >99% ee

Optically pure (>99% ee) cyclopentenone-fused γ-lactones (R,S)-2 were synthesized in high yields (Scheme 3) by using (S)-enallenols 1 which were readily obtained from kinetic resolution of enallenols 1 with Candida antarctica lipase B (CalB).14 This strategy provides an efficient way towards chiral cyclopentenone-fused γ-lactones with high step-economy and selectivity. We next explored the substrate scope for chemoselective formation of γ-lactones 3 (Scheme 4). Enallenols with alkyl, aryl, ester functional groups, and Cyclopentylidene, cyclooctylidene, and unsymmetrical phenyl and methyl substituents worked equally well to afford the γ-lactones 3a-3K in excellent yields. With alkyl or aromatic substituents in R2, R3 and R4 positions, enallenols 1l-1o worked equally well to furnish substituted γ-lactones 3l-3o in good yields. Due to the electronic effect on the olefin moiety, a prolonged reaction time was required for the formation of 3n. Interestingly, a spiro-γ-lactone 3p was obtained with good selectivity in 77% yield under the standard homogeneous reaction conditions. Scheme 4. Scope for selective formation of 3 HO R2 R1 R3

(2m) 52%, >50:1 d.r.

It is noteworthy that the heterogeneous PdII-Amp-MCF catalyst used for the selective formation of cyclopentenone-fused γ-lactone 2 can be recovered and recycled many times without any observed loss of activity or selectivity (Scheme 2). Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) analysis of the liquid aliquot after reaction and hot filtration test during reaction (see Supporting Information, P. S18) showed that there was no detectable leached Pd species during or after the reaction, which rule out that leached Pd species catalyze the reaction as a homogeneous catalyst. Scheme 3. Synthesis of optically pure 2

O

O

O (R,S)-2f 71%, >99% ee

Pd leaching < 0.1 ppm

O

O

O

O O

O

O (2j) 72%, >50:1 d.r.

O

O

Ph O

O

O

O

leaching test

2nd: 78%, >50:1 d.r.

Ph

Me O

R3 R4

O

O

(3R,6S)-2

n-Bu

2

SO

R O H

(S)-1

2

n-Bu O

R

R1 H

CO (1 atm) PdII-AmP-MCF (2 mol %) Methyl-BQ (1.1 equiv) CH2Br2, r.t., 12 h

O

Methyl-BQ (1.1 equiv) CH2Br2, r.t., 12 h

1 atm

1

O

1

OH R1

R4

+

CO 1 atm

1 n-Bu

R3 2 R1 R

Pd(TFA)2 (5 mol %)

O

BQ (1.1 equiv) CH3CO2H (10 mol %) CHCl3, r.t., 12 h

Me

O 3

Ph

Ph

O

O

O 84% (3a)

O 84% (3b)

R4

O

O

O 88% (3c)

O 82% (3d)

EtO2C O

O

O

O 89% (3e)

O 85% (3f)

79% (3g)

n-Bu

n-Bu

O O

O

87% (3i) Me n-Bu O O

72% (3m)

O

80% (3k)

85% (3l)

O

O

Me

Ph n-Bu

n-Bu

n-Bu O

O O 88% (3n, 24 h)

75% (3h)

O Ph

74% (3j)

O

n-Bu Me

n-Bu

O

O

O

O

86% (3o)

O O

77% (3p)

The strategy for chemodivergent and diastereoselective construction of γ-lactones can be extended to the synthesis of γ-lactams. Using enallenamide 1ab as starting material, switchable synthesis of cyclopentenone-fused γ-lactam 2ab and γ-lactam 3ab were achieved in good yields and excellent

ACS Paragon Plus Environment

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

diastereoselectivity under the standard heterogeneous and homogeneous reaction conditions (Scheme 5). Scheme 5. Chemodivergent and diastereoselective synthesis of γ-Lactams Standard homogeneous n-Bu system

n-Bu NTs

Standard heterogeneous system

NHTs

n-Bu

BQ

1 atm

O

R

R

Ph

O

O O

O 4 (R = n-Bu), 90%

O [Ir(COD)Cl]2

n-Bu

O O 5 (R = Ph), 84%, >50:1 d.r.

2

H2 (1 bar) n-Bu

Pd/C

(II) XH Pd

R

O

1

1) allene attack 2) CO

2

red. R elim.

X

R

XH

Pd (II) CO

Pd O (II) Int-A'

O

3

Path a

X

Int-A

Path b CO insertion R

lactonization XH

(II) Pd

XH R

Pd (II)

O Int-C

selective olefin insertion

O Int-B

X = O or NTs

In conclusion, we have developed an efficient palladium-catalyzed oxidative tandem reaction of eanllenols for the chemodivergent and diastereoselective synthesis of γ-lactone and γ-lactam derivatives. Salient features of our findings include: 1) the catalyst controlled chemodivergent carbonylation is achieved by switching between homogeneous and heterogeneous catalysts, which disclose novel opportunities for control of chemoselectivity in carbonylative reactions. 2) The tandem strategy for synthesis of γ-lactones and γ-lactams is atom- and step-economic with high selectivity, which will be beneficial in synthetic chemistry. 3) Construction of enantioenriched cyclopentenone-fused γ-lactones was realized by employing the heterogeneous Pd-catalyzed tandem process on enantiopure enallenols. Further studies on the use of the heterogeneous Pd-AmP-MCF catalyst for other Pd-catalyzed transformations are currently under way in our laboratory.

n-Bu

O O 6, 85%

O O

O

O Int-D

Standard heterogeneous system: PdII-Amp-MCF (2 mol %), Methyl-BQ (1.1 equiv), CH2Br2, rt, 12 h

Bearing multiple carbon-carbon double bonds, γ-lactones 2 and 3 were further transformed to their corresponding hydrogenation derivatives selectively. In the presence of 1 bar of H2, by switching catalyst between [Ir(COD)Cl]2 and Pd/C, we realized the selective hydrogenation of γ-lactones 2 and 3 to mono-hydrogenated products 4 and 6, and to di-hydrogenated products 5 and 7 in high yield and good selectivity (Scheme 6). To be noted, the hydrogenated product cyclopentanone fused γ-lactone 5 was obtained as a single diastereoisomer with four chiral centers. In addition, the single crystal structure of 5 (Scheme 6, for details, see Supporting Information, P. S35, 36) further confirmed the cis-conformation of the cyclopentenone-fused γ-lactone skeleton in product 2.13 Scheme 6. Selective hydrogenation of 2 and 3

Pd (II)

X

Standard homogeneous system: Pd(TFA)2 (5 mol %), BQ (1.1 equiv), AcOH (10 mol %), CHCl3, rt, 12 h

n-Bu

R

R

lactonization

2ab 78%, > 50:1 d.r.

R

XH

HQ

Pd(0)

Ts N

O

1ab

Pd(II) XH

O

+ CO

O 3ab 82%

Page 4 of 6

O O

3

ASSOCIATED CONTENT

O O 7, 92%

Supporting Information

Based on the experimental results and our previous work on Pd(II)-catalyzed oxidative carbocyclization of allene derivatives,5 a plausible mechanism for the chemodivergent and diastereoselective synthesis of γ-lactones and γ-lactams is given in Scheme 7. As the initial step, simultaneous coordination of the hydroxyl group (sulfonamide group), allene and olefin unit to the Pd(II) center would promote the allene attack and then CO coordination to form Int-A. In the presence of homogeneous Pd, attack by the XH group on coordinated CO would be favored with formation of Int-A´ and give γ-lactones or γ-lactams 3 as the product after reductive elimination (path a), while in the presence of heterogeneous Pd, CO insertion into the Pd–C bond of Int-A would be favored, affording Int-B (path b). Lactonization or lactamization of Int-B could also lead to γ-lactones or γ-lactams 3, while selective olefin insertion in Int-B directed by the OH group (for control experiment on diastereoselectivity, see Supporting Information, P. S34) or NHTs group would produce Int-C. In Int-C the alkyl palladium and hydroxyl group (sulfonamide group) are on the same side of cyclopentenone moiety. Further CO insertion of Int-C would produce Int-D, which would undergo lactonization or lactamization to give cyclopentenone-fused γ-lactones or γ-lactams 2. Scheme 7. Proposed mechanism

Experimental procedures and compound characterization data, including the 1H/13C NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author *[email protected] *[email protected]

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT Financial support from the European Research Council (ERC AdG 247014), The Swedish Research Council (2016-03897), the Berzelii Center EXSELENT, and the Knut and Alice Wallenberg Foundation (KAW 2016.0072) is gratefully acknowledged.

REFERENCES (1) For selected books and reviews, see: (a) Natural Lactones and Lactams: Synthesis, Occurrence and Biological Activity, 1st ed.; Janecki, T., Ed.; Wiley-VCH: Weinheim, Germany, 2013. (b)

ACS Paragon Plus Environment

Page 5 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Kumar, A.; Singh, V.; Ghosh, S. Butenolide: A Novel Synthesis and Biological Activities, 1st ed.; LAP LAMBERT Academic Publishing: Saarbrücken, Germany, 2012. (c) Churchill M. E. A.; Chen, L. Chem. Rev. 2011, 111, 68. (d) Schulz, S.; Hötling, S. Nat. Prod. Rep. 2015, 32, 1042. (e) Ren, Y.; Yu, J.; Kinghorn, A. D. Curr. Med. Chem. 2016, 23, 2397. For a recent example on γ-lactone based recyclable polymer, see: (f) Zhu, J.-B.; Watson, E. M.; Tang, J.; Chen, E. Y.-X. Science 2018, 360, 398. (2) For selected books and reviews, see: (a) Ogliaruso, M. A.; Waefe, J. F. Synthesis of Lactones and Lactams; John Wiley: New York, 2010. (b) Yanai, H. Chapter 10 – Green and Catalytic Methods for γ-Lactone Synthesis. Green Synthetic Approaches for Biologically Relevant Heterocycles; Brahmachari, G., Ed.; Elsevier: Boston, 2015. (c) Kitson, R. R. A.; Millemaggi, A.; Taylor, R. J. K. Angew. Chem., Int. Ed. 2009, 48, 9426. (d) Kammerer, C.; Prestat, G.; Madec, D.; Poli, G. Acc. Chem. Res. 2014, 47, 3439. (e) Mao, B.; Fañanás-Mastral, M.; Feringa, B. L. Chem. Rev. 2017, 117, 10502. For recent examples, see: (f) Zhou, J.; Fu, C.; Ma, S. Nat. Commun. 2018, 9, 1654. (g) Conway, J. H.; Rovis, T. J. Am. Chem. Soc. 2018, 140, 135. (3) For selected examples, see: (a) Davies, J. J.; Krulle, T. M.; Burton, J. W. Org. Lett. 2010, 12, 2738. (b) Schnermann, M. J.; Beaudry, C. M.; Genung, N. E.; Canham, S. M.; Untiedt, N. L.; Karanikolas, B. D. W.; Sütterlin, C.; Overman, L. E. J. Am. Chem. Soc. 2011, 133, 17494. (c) Newhouse, T. R.; Kaib, P. S. J.; Gross, A. W.; Corey, E. J. Org. Lett. 2013, 15, 1591. (d) Liang, R.; Chen, K.; Zhang, Q.; Zhang, J.; Jiang, H.; Zhu, S. Angew. Chem., Int. Ed. 2016, 55, 2587. (4) For selected book and reviews, see: (a) Metal Catalyzed Cascade Reactions, 1st ed.; Müller, T. J. J., Ed.; Springer-Verlag: Berlin Heidelberg, 2006. (b) Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248, 2365. (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134. (d) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167. (e) Volla, C. M. R.; Atodiresei, I.; Rueping, M. Chem. Rev. 2014, 114, 2390. (5) For reviews, see: (a) Piera, J.; Bäckvall, J.-E. Angew. Chem. Int. Ed. 2008, 47, 3506. (b) Deng, Y.; Persson, A. K. Å.; Bäckvall, J.-E. Chem. Eur. J. 2012, 18, 11498. (c) Zhang, D.; Liu, J.; Córdova, A.; Liao, W.-W. ACS Catal. 2017, 7, 7051. (d) Yang, B.; Qiu, Y.; Bäckvall, J.-E. Acc. Chem. Res. 2018, 51, 1520. For selected examples, see: (e) Zhu, C.; Yang, B.; Bäckvall, J.-E. J. Am. Chem. Soc. 2015, 137, 11868. (f) Qiu, Y.; Yang, B.; Zhu, C.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2016, 55, 6520. (g) Qiu, Y.; Yang, B.; Zhu, C.; Bäckvall, J.-E. J. Am. Chem. Soc. 2016, 138, 13846. (h) Qiu, Y.; Yang, B.; Jiang, T.; Zhu, C.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2017, 56, 3221. (i) Zhu, C.; Yang, B.; Qiu, Y.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2016, 55, 14405. (j) Naidu, V. R.; Posevins, D.; Volla, M. R.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2017, 56, 1590. (k) Bartholomeyzik, T.; Pendrill, R.; Lihammar, R.; Jiang, T.; Widmalm, G.; Bäckvall, J.-E. J. Am. Chem. Soc. 2018, 140, 298. (6) For strigolactone, see: (a) Cook, C. E.; Whichard, L. P.; Turner, B.; Wall, M. E.; Egley, G. H. Science 1966, 154, 1198. (b) Akiyama, K.; Matsuzaki, K.; Hayashi, H. Nature 2005, 435, 824. (c) Zwanenburg, B. Pospíšil, T Mol. Plant. 2013, 6, 38. (d) Ueno, K.; Nomura, S.; Muranaka, S.; Mizutani, M.; Takikawa, H.; Sugimoto, Y. J. Agric. Food Chem. 2011, 59, 10485. (e) Johnson, A. W.; Gowda, G.; Hassanali, A.; Knox, J.; Monaco, S.; Razavi, Z.; Rosebery, G. J. Chem. Soc., Perkin Trans. 1 1981, 1734. For sinularone C, see: (f) Shi, H.; Yu, S.; Liu, D.; van Ofwegen, L.; Proksch, P.; Liu, W. Mar. Drugs 2012, 10, 1331. For scrodentoid

F, see: (g) Zhang, L.-q.; Zhao, Y.-y.; Huang, C.; Chen, K.-x.; Li, Y.-m. Tetrahedron 2016, 72, 8031. For didemnenone A, see: (h) Forsyth, C. J.; Clardy, J. J. Am. Chem. Soc. 1988, 110, 5912. (7) (a) Shakeri, M.; Tai, C.-W.; Göthelid, E.; Oscarsson, S.; Bäckvall, J.-E. Chem. Eur. J. 2011, 17, 13269. (b) Johnston, E. V.; Verho, O.; Kärkäs, M. D.; Shakeri, M.; Tai, C.-W.; Palmgren, P.; Eriksson, K.; Oscarsson, S.; Bäckvall, J.-E. Chem. Eur. J. 2012, 18, 12202. (c) Verho, O.; Gustafson, K. P. J.; Nagendiran, A.; Tai, C.-W.; Bäckvall, J.-E. ChemCatChem. 2014, 6, 3153. (d) Nagendiran, A.; Sörensen, H.; Johansson, M. J.; Tai, C.-W.; Bäckvall, J.-E. Green Chem. 2016, 18, 2632. (e) Verho, O.; Zheng, H.; Gustafson, K. P. J.; Nagendiran, A.; Zou, X.; Bäckvall, J.-E. ChemCatChem. 2016, 8, 773. (f) Nagendiran, A.; Pascanu, V.; Gómez, A. B.; Miera, G. G.; Tai, C.-W.; Verho, O.; Martín-Matute, B.; Bäckvall, J.-E. Chem. Eur, J. 2016, 22, 7184. (g) Li, M.-B.; Posevins, D.; Gustafson, K. P. J.; Tai, C.-W.; Shchukarev, A.; Qiu, Y.; Bäckvall, J.-E. Chem. Eur. J. 10. 1002/chem.201805118. (8) For selected books and reviews on chemoselective carbonylation reactions, see: (a) Kollár, L. Modern carbonylation methods; Wiley-VCH: Weinheim, Germany, 2008. (b) Wu, X.-F.; Neumann, H.; Beller, M. Chapter 1 – Transition-Metal-Catalyzed Carbonylative Domino Reactions. Domino Reactions: Concepts for Efficient Organic Synthesis; Tietze, L. F., Ed.; Wiley-VCH: Weinheim, Germany, 2014. (c) Barnard, C. F. J. Organometallics 2008, 27, 5402. (d) Wu, X. F.; Neumann, H.; Beller, M. Chem. Soc. Rev. 2011, 40, 4986. (e) Liu, Q.; Zhang, H.; Lei, A. Angew. Chem., Int. Ed. 2011, 50, 10788. (f) Wu, X. F.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1. (g) Wu, X.-F.; Fang, X.; Wu, L.; Jackstell, R.; Neumann, H.; Beller, M. Acc. Chem. Res. 2014, 47, 1041. (h) Gadge, S. T.; Bhanage, B. M. RSC Adv. 2014, 4, 10367. (i) Shen, C.; Wu, X.-F. Chem. Eur. J. 2017, 23, 2973. (j) Bai, Y.; Davis, D. C.; Dai, M. J. Org. Chem. 2017, 82, 2319. (9) For review on ligand- and solvent-controlled chemoselective carbolylation reactions, see: (a) Peng, J.-B.; Wu, X.-F. Angew. Chem. Int. Ed. 2018, 57, 1152. For selected examples on ligandand solvent-controlled chemoselective carbolylation reactions, see: (b) Liu, J.; Liu, Q.; Franke, R.; Jackstell, R.; Beller, M. J. Am. Chem. Soc. 2015, 137, 8556. (c) Xu, T.; Sha, F.; Alper, H. J. Am. Chem. Soc. 2016, 138, 6629. (10) (a) Taguchi, A.; Schüth, F. Micropor. Mesopor. Mater. 2005, 77, 1. (b) Schmidt-Winkel, P.; Lukens, Jr., W. W.; Zhao, D.; Yang, P.; Chmelka, B.; Stucky, G. D. J. Am. Chem. Soc. 1999, 121, 254. (c) Han, Y.; Lee, S. S.; Ying, J. Y. Chem. Mater. 2006, 18, 643. (11) For TEM images and XPS spectra of PdII-AmP-MCF before and after reaction Supporting Information, P. S9. (12) In one experiment the use of colloidal palladium afforded 25% yield of 2a together with 15% yield of 3a (See Supporting Information, Table S2, entry 12). (13) The relative stereochemistry of 2 was determined by NOESY spectrum of 2a (see Supporting Information, P. S10). Single crystal structure of 5 (CCDC 1865456) synthesized by hydrogenation of 2f (Scheme 6) further confirmed the structure. (14) For the preparation of (S)-1, see the Supporting Information, P. S19

ACS Paragon Plus Environment

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 6

Graphic Abstract XH

R X

R

Homogeneous Pd R

Heterogeneous Pd

CO

CO

O

X O O

up to 89% yield

X = O or NTs

up to 82% yield >50:1 d.r. Chirality transfer (> 99% ee)

 catalyst-controlled chemodivergent carbonylation  Heterogeneous Pd-catalyzed oxidative tandem process  Diastereoselective construction of fused-lactone and lactam

ACS Paragon Plus Environment

6