Synthetic Strategy: Palladium-Catalyzed Dehydrogenation of Carbonyl

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Synthetic Strategy: Palladium-Catalyzed alpha,betaDehydrogenation of Carbonyl Compounds Toshikazu Hirao J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03117 • Publication Date (Web): 22 Jan 2019 Downloaded from http://pubs.acs.org on January 24, 2019

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The Journal of Organic Chemistry

Synthetic Strategy: Palladium-Catalyzed Dehydrogenation of Carbonyl Compounds Toshikazu Hirao The Institute of Scientific and Industrial Research, Osaka University, Mihoga-oka, Ibaraki, Osaka 567-0047, Japan

[email protected]

ABSTRACT: Palladium-catalyzed oxidative -dehydrogenation (oxidative desilylation, decarboxylative dehydrogenation, direct dehydrogenation, and oxidative dehydroboration) of carbonyl compounds and their derivatives to -unsaturated carbonyl compounds via palladium enolate intermediates is reviewed as a versatile synthetic method.

Formation of a carbon-carbon double bond at the 　 positions of carbonyl compounds and their derivatives is a useful synthetic method to functionalize carbonyl compounds in organic synthesis, leading to the construction of carbon molecular frameworks and fuctionalization. This method provides an important and convinced route to activate - and carbons of carbonyl compounds, the latter of which is generally less reactive. For this purpose, various conventional methods have been developed including dehydrogenation, dehydrohalogenation, and dehydrosulfonation. Use of selenide permits the transformation under milder conditions via the selenoxide derived by the trapping of a lithium enolate with PhSeX.1 Another potential method has been developed by Nicolaou, in which a stoichiometric hypervalent iodine oxidant, 2-iodoxybenzoic acid, is used for dehydrogenation.2 A breakthrough method has been for the first time demonstrated by Saegusa, Ito, and Hirao, using the palladiumcatalyzed dehydrosilylation of silyl enolates, which are available from the carbonyl compounds.3 This finding has made it possible to expand chemistry of enolate to transition metal

enolate, which is a potential intermediate in various transition metal-induced or catalyzed reactions, permitting versatile molecular transformations.4 1.

OXIDATIVE DESILYLATION Oxidative transformation of silyl enolates with Pd(II) species results in desilylation to -unsaturated carbonyl compounds as shown in Scheme １． cat. Pd(OAc)2, MeCN

OSiMe3 R

R'

cat. Cu(OAc)2-O2 (or p-benzoquinone)

O R

R'

Scheme 1 The catalytic reaction proceeds in the presence of pbenzoquinone. Furthermore, Cu(OAc)2 has been found to work as a catalytic co-oxidant under molecular oxygen in the palladium(II)-catalyzed dehydrosilylation reaction (Scheme 2).5 Silyl enolates can be prepared regioselectively, which

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allows the regioselective introduction of -carbon-carbon double bond. This reaction is proposed to proceed via palladium enolate, followed by -hydride elimination. When both geometries of an olefinic moiety are possible, the trans-isomer is obtained stereoselectively due to the stereochemistry of the palladium C-enolate for syn -hydride elimination. Exo-cyclic olefin is converted to the corresponding endoone, indicating the olefin migration by hydride palladium species. O2

OSiMe3

Cu(I)X R

Pd(II)X2L2

R'

Cu(II)X2

O Pd(0)L2

H

R

O R'

PdXL2

R

O

Pd(II)

Pd(OAc)2

R'

R

Page 2 of 6

R

R' O

O

Scheme 5 The present reaction is applied to the Pd(OAc)2-induced reaction of aryl iodides with allyl trimethylsilyl ethers in the presence of LiCl to give -aryl trans--unsaturated carbonyl compounds.7 The palladium enolate is present as a key intermediate through the palladium-catalyzed arylation and successive elimination into the silyl enolate as shown in Scheme 6. This method allows the introduction of an aryl group at the -position and oxidation of the hydroxy group. Pd(OAc)2, LiCl

OSiMe3

Ar-I +

Ar

R

R'

Ar

O

OSiMe3

PdXL2 HX

R

R'

SiMe3

R

R

Scheme 6

O

2. DECARBOXYLATIVE DEHYDROGENATION R R' The other route to palladium enolates is attained by Scheme 2　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　 decarboxylation of allyl -keto carboxylates via allyl palladium enolate complexes (Scheme 7).8 A palladium catalyst consisting Furthermore, a combination of the conjugate addition and of dppe (1,2-bis(diphenylphosphino)ethane) is found to work regioselective dehydrosilylation results in regioselective well in acetonitrile. functionalization of -unsaturated carbonyl compounds through the conjugate addition of lithium dialkylcopper species 4 and subsequent silylation, affording -substituted carbonyl O R O O 3 R4 compounds via dehydrosilylation as exemplified by Scheme 3. Pd(II)HXL2

O 1. Me2CuLi

OSiMe3 0.5 molar equiv of Pd(OAc)2

O

cat. Pd(OAc)2, dppe

O

R1 R2

O

R3

R2

R3

Pd (dppe)

R1

0.5 molar equiv of p-benzoquinone

2. Me3SiCl

R

R1

4

R3

R2

Scheme 3

Scheme 7

The palladium enolate intermediate is allowed to undergo the intramolecular cyclization with an olefinic moiety of the starting silyl C-enolate of alkenyl methyl ketone, where a hydrogen for the -hydride elimination is not present (Scheme 4).5

Allyl enol carbonates, which are obtained from ketone enolates and allyl chloroformate, undergo the palladiumcatalyzed decarboxylative -dehydrogenation (Scheme 8).9

O RR'C=C(CH2)nC=CH2 cat. Pd(OAc)2, MeCN OSiMe3 p-benzoquinone

OCO2

O R

(CH2)n CHRR'

R

4

1

R2

R

H

1

R2

R3

O (CH2)n

R4

ClCO2

R3 O

cat. Pd(OAc)2, dppe

R4

R1

Pd(II)

O

C RR'

Scheme 4

R1

Another route to palladium enolates is achieved by oxidative conversion of -epoxysilanes to give trans--unsaturated carbonyl compounds via the palladium C-enolates, where the carbonyl group appears on the carbon originally bearing the silyl group (Scheme 5).6

R2

R

4

R2

R3

Pd (dppe) R3

Scheme 8 　 The reaction course shown in Scheme 8 depends on the solvent. In acetonitrile, the main route is decarboxylationdehydrogenation to give -unasaturated carbonyl compounds.


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The Journal of Organic Chemistry In contrast, decarboxylation-allylation is observed in THF or benzene. In the dehydrogenation step, the allyl group serves as a hydrogen acceptor (Scheme 9). O O

R1 R

R

R

3

R2

O

4

R1

R R3

1

R2

R4

R1

R3

R3

R2

OPdLn(allyl)

OCO2

R2

R4 PdLn (allyl)

1

Pd(0)Ln

R

cat. [Pd(allyl)Cl]2, Zn(TMP)2 O

4 O R O

2

O

O

O

R4

R

R4

1

Scheme 12 The generation of zinc enolate or (cyanoalkyl)zinc species　 (LiCyan ＋ ZnCl2) followed by the addition of a catalytic amount of [Pd(allyl)Cl]2 and allyl pivalate as an allyl oxidant also permits -dehydrogenation of esters, lactones and nitriles (Scheme 13).13 The reaction course is explained by hydride elimination and propene-forming reductive elimination (Scheme 14).

R3

R2

R3

Scheme 9 R

The palladium-dppe complex derived from allyl carbonate also catalyzes the oxidation of silyl enolates of ketones or aldehydes, ketene silyl acetals of esters and lactones to the corresponding -unsaturated carbonyl compounds (Scheme 10).10 Use of phosphine free palladium catalyst results in a higher selectivity for the dehydrogenation. OCO2R

Pd(0)Ln -CO2

PO(OEt)2

EWG

ester, lactone, nitrile

1. LiCyan and ZnCl2, or Zn(TMP)2-2LiCl

Pr-i N Li

i-Pr

(LiCyan)

Scheme 13 EWG

Pd(allyl)(Ln)OR

EWG

R

OPiv

2. cat. [Pd(allyl)Cl]2,

EWG

catalyst for -dehydrogenation of silyl enolate silyl ketene acetal enol acetate

Pd(II)L2

M

R R

EWG

R

H Pd(II)L2

Scheme 10

Pd(II)L2

3.

DIRECT DEHYDROGENATION In the presence of allyl diethyl phosphate, Pd(OAc)2 catalyzes the -dehydrogenation of aldehydes and cyclic ketones under basic conditions (sodium bicarbonate) to give the -unsaturated carbonyl compounds (Scheme 11).11 Allyl palladium diethyl phosphate might be involved as an intermediary catalyst. The allylation reaction does not compete in this catalytic system. O R

H +

O

OPiv

Similarly, the palladium-catalyzed oxidation dehydrogenation of carboxylic acids to 2-enoic acids also proceeds smoothly by use of Zn(TMP)2 (Scheme 15).14 cat. [Pd(allyl)Cl]2, Zn(TMP)2, OAc

O R

H

H

Scheme 14

PO(OEt)2 + NaHCO3

cat. Pd(OAc)2

Pd(0)L2

COOH

Scheme 11

R

After zinc enolate is generated from cyclic ketone and Zn(TMP)2, 　 (TMP: 2,2,6,6-tetramethylpiperidine), [Pd(allyl)Cl]2 catalyzes the -dehydrogenation in the presence of allyl diethyl phosphate as an above-mentioned oxidant (Scheme12).12

Scheme 15

R

COOH

Amides are successfully converted to the corresponding -unsaturated ones by treatment of lithium N-cyclohexyl anilide (LiCyan), ZnCl2, a catalytic amount of [Pd(allyl)Cl]2 in this order (Scheme 16).15 The similar direct catalytic method is also performed for the α,β-dehydrogenation of N-protected lactams to give their conjugated unsaturated counterparts under mild conditions.16



OAc NR'2

R

O R

NR'2

LiCyan

Scheme 16 Direct catalytic aerobic oxidation reaction under molecular oxygen is achieved as follows. Pd(OAc)2 in the presence of 2 equiv of NaOAc in DMSO under molecular oxygen serves an oxidation catalyst for -dehydrogenation of aldehydes and ketones (Scheme 17).17 O

O cat. Pd(OAc)2, Na(OAc)2, DMSO O2

Scheme 17 The palladium catalytic system consisting of TFA (trifluoroacetate) and FCA (4,5-diazafluorenone) is found to serve efficiently in the aerobic -dehydrogenation reaction.18,19 O FCA

N

N

Pd(DMSO)2(TFA)2 catalyzes dehydrogenation of cyclohexanones and cyclic ketones under molecular oxygen as an oxidant to give the corresponding enones (Scheme 18).20,21 The modest regioselectivty is observed in the case of substituted cyclohexanones. The higher selectivity for -unsaturated enone than phenol formation is achieved by this catalytic system. DMSO is demonstrated to play an important role to control the oxidation reaction. The aromatization of cyclohexanones occurs with ortho-dimethylaminopyridine ligand to give phenols through successive dehydrogenation of two saturated carbon-carbon bonds of the six-membered ring, where molecular oxygen serves as a hydrogen acceptor.22

O

cat. Pd(TFA)2, ligand, p-TsOH

and cross-coupling27 reactions of boron enolates to give the 1,4-dicarbonyl compounds chemoselectively. These findings suggest that the scission of boron-oxygen bond is induced by metallic oxidants, which permits the investigation on novel fuctionalization of boron enolates with metallic oxidants. A variety of synthetic methods for -dehydrogenation of carbonyl compounds have been developed under milder reaction conditions as mentioned above. If another route to palladium enolates is available, an alternative protocol could be developed. The more reactive dehydrogenative transformation is attained as follows. The palladium(II)-catalyzed dehydroboration of boron enolates is demonstrated to be achieved to give -unsaturated ketones (Scheme 19). Boron enolates are prepared with ease only by modified synthesis of ketones with commercially available B-I-9-BBN (9-iodo-9borabicyclo[3.3.1]nonane) in the presence of (i-Pr)2NEt (DIEA).28 The solution of thus-obtained boron enolate is successively treated with a stoichiometric amount of Pd(OAc)2 to give the desired product.29 The palladium enolate is suggested to be involved as a key intermediate, giving the -unsaturated ketone via elimination of a Pd-H species (Scheme 19). The reduced palladium species is likely to be re-oxidized with Cu(II) cooxidant to regenerate an active palladium(II) species for the catalytic cycle (Scheme 20). Actually, the catalytic efficiency is observed in the case of the reaction with a catalytic amount of PdCl2(PhCN)2 in the presence of Cu(II) species (Scheme 19) Cu(OAc)2 is found to be superior to CuCl2 as a co-oxidant to CuCl2. 26

cat. [Pd(allyl)Cl]2, ZnCl2, O

Page 4 of 6

I B (B-I-9-BBN) DIEA

O R

R'

O R

MS4A cat. PdCl2(PhCN)2, Cu(OAc)2

R

R'

Scheme 19

O2 (1 atm), DMSO R

R'

O

MS4A

O

B

R

O

2Cu(I)X

OH

Pd(II)X2L2

B

R

R'

2Cu(II)X2 9-BBN-X

R Scheme 18 4.

OXIDATIVE DEHYDROBORATION During the investigation on the interaction between Pd and hetero atom species,23 I developed the palladium-catalyzed phosphonation24 as c,arbon-hetero atom cross-coupling reaction. From this point of view, boron enolates have been employed as a substrate in the present dehydrogenation.. Boron enolates are mostly used in the cross-aldol reaction.25 Quite recently, we demonstrated the vanadium-induced homo-

O Pd(0)L2

R

H

O

R' PdXL2

HX

R

PdXL2 R'

O Pd(II)HXL2

R

R'

Scheme 20 The boron enolates derived from linear and cyclic ketones undergo the stereoselective dehydroboration. The trans--


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The Journal of Organic Chemistry unsaturated carbonyl compound is preferentially obtained in the case that both cis- and trans-isomers could be formed. The conformation of the C-enolate is considered to control this olefinic geometry, where syn -elimination leads to the transisomer. The competitive reaction of silyl enolate and boron enolates in the stoichiometric reaction with Pd(OAc)2 results in the exclusive formation of the oxidation product from the boron enolate, indicating that the reactivity of boron enolate towards Pd(II) species is higher than that of silyl enolate. This finding permits us to differentiate these enolates effectively. The abovementioned methods are allowed to provide a synthetically versatile route from ketones to -unsaturated ketones. The mechanistic and application aspects wait for further investigation. 5.

APPLICATION Application of the present -dehydrogenation is demonstrated by -alkylation of ketones and aldehydes with alkyl bromides. The palladium-catayzed redox-cascade strategy is permitted to be achieved as shown in Scheme 21.30

O +

Br

cat. Pd(OAc)2 P(i-Pr)3HBF4 cat. Cu(OPiv)2 CsCO3

O

O +

Scheme 21 The palladium-catalyzed oxidative -stannylation or alkylation of enones affords the useful building block in organic synthesis as illustrated in Scheme 22A and B.31

O

A. Bu3SnLi or PhMe2SiLi cat. [Pd(allyl)Cl]2 allyl diethyl phosphate B. R'3ZnM cat. [Pd(allyl)Cl]2 allyl diethyl phosphate

O

R

R = Bu3Sn, PhMe2Si, R' Scheme 22 6.

CONCLUSIONS The stereoselective formation of a carbon-carbon double bond at the  -positions of carbonyl compounds induced by the palladium-catalyzed oxidation32 provides a versatile synthetic method under the milder reaction conditions. Palladium-catalyzed oxidative desilylation of silyl enolates and -epoxysilanes leads to a route to -nsaturated.carbonyl compounds. Decarboxylative dehydrogenation and direct dehydrogenation are also catalyzed by palladium catalyst. The more facile palladium-catalyzed oxidative transformation is performed with the in-situ generated boron enolates. These

methods are convinced to play an important protocol to prepare the key synthetic intermediates in the multistep synthesis of electronic materials pharmaceuticals, and biologically active compounds.33 AUTHOR INFORMATION Toshikazu Hirao graduated in 1973 from Kyoto University, obtained his doctorate in 1978. He became Assistant Professor at Graduate School of Engineering, Osaka University and was a postdoctoral fellow at The University of Wisconsin with Professor Barry M. Trost (1981–1982). Dr. Hirao was promoted to Associate Professor in 1992 and Professor in 1994. After retirement in 2015, he became Specially Appointed Professor at The Institute of Scientific and Industrial Research, Osaka University. Dr. Hirao’s research interests lie in the area of the construction of efficient systems for electron transfer, which allows the development of new methods in organic synthesis, and novel redox-active systems consisting of transition metal complexes and π-conjugated polymers or oligomers including π bowls (sumanene and its derivatives). These research areas are correlated to the development of bioorganometallic conjugates. REFERENCES (1) (a) Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. Electrophilic and Nucleophilic Organoselenium Reagents. New Routes to -Unsaturated Carbonyl Compounds. J. Am. Chem. Soc., 1973, 95, 6137-6139; (b) Reich, H. J.; Reich, I. L.; Renga, J. M. Organoselenium Chemistry. -Phenylseleno Carbonyl Compounds as Precursors for -Unsaturated Ketones and Esters. J. Am. Chem. Soc., 1973, 95, 5813–5815. (2) (a) Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. A New Methodfor the One-step Synthesis of -Unsaturated Carbonyl Systems from Saturated Alcohols and Carbonyl Compounds. J. Am. Chem. Soc., 2000, 122, 7596-7597; (b) Nicolaou, K. C.; Montagnon, T.; P. S. Baran, P. S.; Zhong, Y.-L. Iodine(V) Reagents in Organic Synthesis. Part 4. o-Iodoxybenzoic Acid as a Chemospecific Tool for Single Electron Transfer-Based Oxidation Processes. J. Am. Chem. Soc., 2002, 124, 2245-2258. (3) Ito, Y.; Hirao, T.; Saegusa, T. Synthesis of -Unsaturated Carbonyl Comounds by Palladium-Catalyzed Dehydrosilylation of Silyl Enol Ethers. J. Org. Chem., 1978, 43, 1011-1013. (4) For example, (a) Hirao, T.; Harano, Y.;.Yamana, Y.; Ohshiro, Y.; Agawa, T. Tetracarbonyl Nickel Induced Reaction of gem-Dibromocyclopropanes with Alcohols or Amines. Versatile Synthesis of Cyclopropanecarboxylic Acid Derivatives. Tetrahedron Lett., 1983, 24, 1255-1258; (b) Hirao, T.;. Nagata, S.; Yamana, Y.; Agawa, T. Nickel Enolates in the Ni(CO)4-Induced Carbonylation of gemDibromocyclopropanes with Silylamine or Silylsulfide. Tetrahedron Lett., 1985, 26, 5061-5064; (c) Hirao, T.; Nagata, S.; Agawa, T. Synthesis of -Unsaturated Carboxylic Acid Derivatives by the Novel Ni(CO)4-Induced Ring-Opening Carbonylation Reaction of 1,1-Dibromo-2chlorocyclopropanes. Chem. Lett., 1985, 1625-1628.



(5) Ito, Y.; Aoyama, H.; Hirao, T.; Mochizuki, A.; Saegusa, T. Cyclization Reactions via Oxo--allylpalladium(II) Intermediates. J. Am. Chem. Soc., 1979, 101, 494-496. (6) Hirao, T.; Yamada, N; Ohshiro, Y.; Agawa, T. PalladiumPromoted Transformation of -Epoxysilanes to Unsaturated Carbonyl Compounds. Chem Lett., 1982, 19972000. (7) Hirao, T.; Enda, J.; Ohshiro, Y.; Agawa, T. PalladiumPromoted Reaction of Allyl Trimethylsilyl Ethers with Aryl Iodides. Chem. Lett., 1981, 403-406. (8) Shimizu, I.; Tsuji, J. Palladium-Catalyzed DecarboxylationDehydrogenation of Allyl -Keto Carboxylates and Allyl Enol Carbonates as a Novel Synthetic Method for -Substituted Unsaturated Ketones. J. Am. Chem. Soc., 1982, 104, 58445847. (9) Shimizu, I.; Minami, I.; Tsuji, J. Palladium-Catalyzed Synthesis of Unsaturated Ketones from Ketones via Allyl Enol Carbonates. Tetrahedron Lett., 1983, 24, 1797-1800 (1983). (10) Minami, I.; Takahashi, K.; Shimizu, I.; Kimura, T.; Tsuji,　 J. New Synthetic Methods for -Unsaturated Ketones, Aldehydes, Esters and Lactones by the Palladium-Catalyzed Reactions of Silyl Enol Ethers, Ketene Silyl Acetals, and Enol Acetates with Allyl Carbonates. Tetrahedron, 1986, 42, 29712977. (11) Shvo, Y.; Haj, A.; Arisha, I. Regioselective Catalytic Dehydrogenation of Aldehydes and Ketones. J. Org. Chem., 1998, 63, 5640-5642. (12) Huang, D.; Zhao, Y. Newhouse, T. R. Synthesis of Cyclic Enones by Allyl-Palladium-Catalyzed -Dehydrogenation. Org. Lett., 2018, 20, 684-687. (13) Chen, Y.; Romaire, J. P.; Newhouse, T. R. PalladiumCatalyzed -Dehydrogenation of Esters and Nitriles. J. Am. Chem. Soc., 2015, 137, 5875-5878. (14) Zhao, Y.; Chen, Y. Newhouse, T. R. Allyl-PalladiumCatalyzed -Dehydrogenation of Carboxylic Acids via Enediolates. Angew. Chem. Int. Ed., 2017, 56, 13122-13125. (15) Chen, Y.; Turlik, A. ； Newhouse, T. R. Amide Dehydrogenation Using Allyl-Palladium Catalysis and a Hindered Monodentate Anilide. J. Am. Chem. Soc., 2016, 138, 1166-1169. (16) Chen, M.; Dong, G. Direct Catalytic Desaturation of Lactams Enabled by Soft Enolization. J. Am. Chem. Soc., 2017, 139, 7757–7760 (17) Larock R. C.; Hightower, T.; Kraus, G. A.; Hahn, P.; Zheng, D. A Simple, Effective, New, Palladium-Catalyzed Conversion of Enol Silanes to Enones and Enals. Tetrahedron Lett., 1995, 36, 2423-2426. (18) Gao, W.; He, Z.; Qian, Y.; Zhao, J.; Huang, Y. General Palladim-Catalyzed Aerobic Dehydrogenation to Generate Double Bonds. Chem. Sci., 2012, 3, 883-886. (19) Diao, T.; Wadzinski, T. J.; Stahl, S. S. Direct Aerobic Dehydrogenation of Aldehydes and Ketones with a Pd(TFA)2/4,5-diazafluornone Catalyst. Chem. Sci., 2012, 3, 887-891. (20) Diao, T.; Stahl, S. S. Synthesis of Cyclic Enones via Direct Palladium-Catalyzed Aerobic Dehydrogenation of Ketones. J. Am. Chem. Soc., 2011, 133, 14566-14568.

(21) Diao, T.; Pun, D.; Stahl, S. S. Aerobic Dehydrogenation of Cyclohexanone to Cyclohexenone Catalyzed by Pd(DMSO)2(TFA)2: Evidence for Ligand-Controlled Chemoselectivity. J. Am. Chem. Soc., 2013, 135, 8205-8212. (22) Izawa, Y.; Pun, D.; Stahl, S. S. Palladium-Catalyzed Aerobic Dehydrogenation of Substituted Cyclohexanones to Phenols. Science, 2011, 333, 209-213. (23) Hirao, T.; Enda, J.; Ohshiro, Y.; Agawa, T. Synthesis of Vinylsilanes by Palladium-Catalyzed Reaction of Trimethylsilylallyl Acetates with Nucleophiles. Tetrahedron Lett., 1981, 22, 3079-3080. (24) (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Stereoselective Synthesis of Vinylphosphonate. Tetrahedron Lett. 1980, 21, 3595-3598; (b) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. A Novel Synthesis of Dialkyl Arenephosphonates. Synthesis 1981, 56; (c) Kohler, M.; Sokol. J. G.; Stockland, Jr., R. A. Development of a room temperature Hirao reaction. Tetrahedron Lett, 2009, 50, 457-459. (25) Mukaiyama, T. Explorations into New Reaction Chemistry. Angew. Chem. Int. Ed., 2004, 43, 5590-5614. (26) Amaya, T.; Masuda, T.; Maegawa, Y.; Hirao, T. Oxovanadium(V)-Induced Diastereoselective Oxidative Homocoupling of Boron Enolate. Chem. Commun., 2014, 50, 2279-2281. (27) Amaya, T.; Maegawa, Y.; Masuda, T.; Osafune, Y.; Hirao, T. Selective Intermolecular Oxidative Cross-Coupling of Eolates. J. Am. Chem. Soc., 2015, 137, 10072-10075. (28) Brown, H. C.; Dhar, R. K.; Bakshi, R. K.; Pandiarajan, P. K.; Singram, B. Major Effect of the Leaving Group in Dialkylboron Chlorides and Triflates in Controlling the Stereospecific Conversion of Ketones into Either [E]- or [Z]Enol Borinates. J. Am. Chem. Soc., 1989, 111, 3441-3442. (29) Sakamoto, Y.; Amaya, T.; Suzuki, T.; Hirao, T. PalladiumCatalyzed Dehydroboration via Generation of Boron Enolates. Chem. Eur. J., 2017, 22, 18686-18689. (30) Wang C.; Dong, G. Direct -Alkylation of Ketones and Aldehydes via Pd-Catalyzed Redox Cascade. J. Am. Chem. Soc., 2018, 140, 6057-6061. (31) Schuppe, A. W.; Huang, D.; Chen, Y.; Newhouse, T. R. Total Synthesis of (-)-Xylogranatopyridine B via a PalladiumCatalyzed Oxidative Stannylation of Enones. J. Am. Chem. Soc., 2018, 140, 2062-2066. (32) Related reviews (a) Muzart, J. One-Pot Syntheses of Unsaturated Carbonyl Compounds through PalladiumMediated Dehydrogenation of Ketones, Aldehydes, Esters, Lactones and Amides. Eur. J. Org. Chem., 2010, 3779-3790; (b) Stahl, S. S.; Diao, T. Oxidation Adjacent to C=X Bonds by Dehydrogenation. Comp. Org. Synth. 2014, 7, 178-212; (c) Turlik, A.; Chen, Y. Newhouse, T. R. Dehydrogenation Adjacent to Carbonyls Using Palladium-Allyl Intermediates. Synlett, 2016; 27, 331-336; (d) Iosub, A. V.; Stahl, S. S. Palladium-Catalyzed Aerobic Dehydrogenation of Cyclic Hydrocarbons for the Synthesis of Substituted Aromatics and Other Unsaturated Products. ACS. Catal. 2016, 6, 8201-8213. (33) One example, Ohshima, T.; Xu, Y.; Takita, R.; Shimizu, S.; Zhong, D.; Shibasaki, M. Enantioselective Total Synthesis of (−)-Strychnine Using the Catalytic Asymmetric Michael Reaction and Tandem Cyclization. J. Am. Chem. Soc., 2002, 124, 14546-14547.


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Synthetic Strategy: Palladium-Catalyzed Dehydrogenation of Carbonyl

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