Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cyclization of 1,6-Enynes

Letter pubs.acs.org/OrgLett

Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cyclization of 1,6-Enynes with Aliphatic and Aromatic Alkenes Hiroki Ueda, Koji Masutomi, Yu Shibata, and Ken Tanaka* Department of Chemical Science and Engineering, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8550, Japan S Supporting Information *

ABSTRACT: It has been established that a cationic rhodium(I)/(R)-MeO-BIPHEP complex catalyzes the asymmetric [2 + 2 + 2] cyclization of 1,6-enynes with aliphatic and aromatic alkenes to produce chiral cyclic dienes through β-hydride elimination from rhodacycle intermediates. Thus, obtained chiral cyclic dienes could be converted to chiral spirocompounds without racemization.

T

corresponding cycloaddition using unfunctionalized aliphatic and aromatic alkenes has not been reported.10−12 In this paper, we were pleased to find that the cationic rhodium(I)/axially chiral biaryl bisphosphine complex is able to catalyze the asymmetric [2 + 2 + 2] cyclization of 1,6-enynes with unfunctionalized aliphatic and aromatic alkenes to produce chiral cyclic dienes with high yields and ee values through βhydride elimination from rhodacycle intermediates (Scheme 1, bottom). We first examined the reaction of 1,6-enyne 1a and excess 1hexene (2a, 5 equiv) in the presence of the cationic rhodium(I)/(R)-H8-BINAP catalyst. Pleasingly, 2a coupled with 1a at room temperature; however, not bicyclic cyclohexene but monocyclic diene 3aa was obtained in good yield with a high ee value (Table 1, entry 1). Screening of axially chiral biaryl bisphosphine ligands (Figure 1, entries 1−5)

he transition-metal-catalyzed asymmetric [2 + 2 + 2] cycloaddition of 1,6-enynes with unsaturated compounds is a useful method for the stereoselective construction of chiral cyclic frameworks.1 For this transformation, cationic rhodium(I)/axially chiral biaryl bisphosphine complexes are known as highly active and selective catalysts.2 The asymmetric [2 + 2 + 2] cycloaddition with alkynes was first reported in 2005 by the Evans and Shibata groups.3 Following this pioneering work, our research group reported the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed asymmetric [2 + 2 + 2] cycloaddition of 1,6-enynes with carbonyl compounds.4,5 On the other hand, the [2 + 2 + 2] cycloaddition of 1,6-enynes with alkenes was first reported in 1999 by the Montgomery group using a nickel(0)/PPh3 complex as a catalyst and enones as alkenes.6,7 Asymmetric variants of this cycloaddition were succeeded by our research group using the cationic rhodium(I)/axially chiral biaryl bisphosphine complexes as catalysts, and acrylamides,8 enamides,9 and vinyl carboxylates9 as alkenes (Scheme 1, top). All the above precedents employed functionalized alkenes as cycloaddition partners, while the

Table 1. Optimization of Reaction Conditionsa entry

ligand

Rh (mol %)

2a (equiv)

yield (%)b

ee (%)

1 2 3 4 5 6 7c

(R)-H8-BINAP (R)-BINAP (R)-Segphos (R)-Difluorphos (R)-MeO-BIPHEP (R)-MeO-BIPHEP (R)-MeO-BIPHEP

10 10 10 10 10 10 5

5 5 5 5 5 2 5

72 67 54 59 71 47 70

91 96 98 95 99 99 99

Scheme 1

a

[Rh(cod)2]BF4 (0.010 mmol), ligand (0.010 mmol), 1a (0.10 mmol), 2a (0.20−0.50 mmol), and CH2Cl2 (1.5 mL) were used. bIsolated yield. c[Rh(cod)2]BF4 (0.010 mmol), ligand (0.010 mmol), 1a (0.20 mmol), 2a (1.0 mmol), and CH2Cl2 (1.5 mL) were used. Received: April 16, 2017 Published: May 22, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acs.orglett.7b01149 Org. Lett. 2017, 19, 2913−2916

Letter

Organic Letters Scheme 2a

Figure 1. Structures of axially chiral biaryl bisphosphine ligands.

revealed that the use of (R)-MeO-BIPHEP afforded 3aa in good yield with the highest ee value (entry 5). Unfortunately, decreasing the amount of 2a to 2 equiv lowered the yield of 3aa (entry 6), but the catalyst loading could be reduced to 5 mol % without erosion of the product yield and ee value (entry 7). With the optimized reaction conditions in hand, we tested the generality of the reaction by using (R)-MeO-BIPHEP as a ligand at room temperature (Scheme 2). With regard to aliphatic alkenes, a variety of aliphatic alkenes 2a−d, possessing no heteroatoms, reacted with 1a to give the corresponding dienes 3aa−ad in good yield with excellent ee values. Heteroatom-substituted aliphatic alkenes 2e−g could also be employed for this process to give the corresponding dienes 3ae−ag with excellent ee values, although the yield of 3af, derived from acetoxy-substiuted alkene 1f, was moderate. Importantly, styrene (1h) could also have been employed for this process to give the corresponding dienes 3ah with a perfect ee value. However, the yield of 3ah was moderate (41%) and regioisomeric product 4ah was also generated in 19% yield. Interestingly, the electronic nature of styrenes significantly affected the yields and regioselectivities of the products. The use of electron-deficient styrene 2i significantly decreased the combined product yield (3 + 4) and the ratio of 3/4. In contrast, the use of electron-rich styrenes 2j and 2k significantly increased the combined product yields (3 + 4) and the ratios of 3/4. With regard to the substituent R1 of 1,6-enynes, not only methyl- (1a) but also ethyl-substituted 1,6-enyne 1b reacted with 2a to give the corresponding diene 3ba in good yield with a perfect ee value. With regard to the linker of 1,6-enynes, not only malonate- (1a and 1b)13 but also sulfonylamide-linked 1,6-enynes 1c and 1d reacted with 2a, 2c, and 2k to give the corresponding dienes 3ca, 3cc, 3ck/4ck, and 3dk/4dk, although the product yields were moderate. With regard to the substitutent R2 of 1,6-enynes, ethyl-substituted 1,6-enyne 1e was also capable of reacting with 2e to give the corresponding diene isomerization product 5 in high yield with a perfect ee value, although a high catalyst loading was required. The absolute configuration of (−)-3dk was unambiguously determined to be R by an X-ray crystallographic analysis (Figure 2). Plausible mechanisms for the formation of 3 and 4 are shown in Scheme 3. 1,6-Enyne 1 reacts with rhodium to generate rhodacyclopentene A. Regioselective insertion of aliphatic alkenes 2a−g into A generates rhodacycle B. Regioselectivity may be rationalized by steric repulsion between the alkene substituent and the ligand, and connecting the electron-rich βcarbon to the electron-deficient cationic rhodium. β-Hydride elimination followed by reductive elimination proceeds to give diene 3. On the other hand, regioisomeric products 4 were also generated in the reactions of styrenes 2h−k, presumably due to

a [Rh(cod)2]BF4 (0.010 mmol), (R)-MeO-BIPHEP, (R)-BINAP, or (R)-H8-BINAP (0.010 mmol), 1 (0.20 mmol), 2 (1.00 mmol), and CH2Cl2 (1.5 mL) were used. The cited yields are of the isolated products. b[Rh(cod)2]BF4 (0.050 mmol), (R)-MeO-BIPHEP, (0.050 mmol), 1 (1.00 mmol), 2 (5.00 mmol), and CH2Cl2 (7.5 mL) were used. c2c (1.0 mL) and CH2Cl2 (1.5 mL) were used. d[Rh(cod)2]BF4 (0.040 mmol) and (R)-H8-BINAP (0.040 mmol) were used.

the relatively electron-rich nature of the α-carbon of 2h−k. The effect of the electronic nature of styrenes on product yields and regioselectivity can be explained as follows. As the formation of rhodacycle B may be more facile than that of rhodacycle C due to smaller steric hindrance in B than C, increasing the electron density of the β-carbons of styrenes 2j and 2k facilitates the formation of B, which increases the combined product yields (3 + 4) and the ratios of 3/4. In contrast, decreasing the electron density of the β-carbon of styrene 2i deters the formation of B, which decreases the combined product yield (3 + 4) and the ratio of 3/4. Alternatively, rhodacycle C may be formed through rhodacycle D. 2914

DOI: 10.1021/acs.orglett.7b01149 Org. Lett. 2017, 19, 2913−2916

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Organic Letters Scheme 5

Figure 2. ORTEP drawing of (R)-(−)-3dk with ellipsoids at 30% probability.

Scheme 6

Scheme 3

Treatment of diene products 3ck (99% ee) and 3dk (>99% ee) with a catalytic amount of BF3·OEt2 (10 mol %) at 0 °C afforded the corresponding spirocompounds 8ck and 8dk, respectively, with high yields and diastereoselectivity without racemization via the intramolecular Friedel−Crafts reaction.15 In conclusion, we have established that a cationic rhodium(I)/(R)-MeO-BIPHEP complex catalyzes the asymmetric [2 + 2 + 2] cyclization of 1,6-enynes with aliphatic and aromatic alkenes to produce chiral cyclic dienes through β-hydride elimination from rhodacycle intermediates. Interestingly, in the reactions of aromatic alkenes, their electronic nature significantly affected the product yields and regioselectivity. Thus, obtained chiral cyclic dienes could be converted to chiral spirocompounds without racemization.

If this pathway is a major contribution, decreasing the amount of styrene 2h with respect to 1,6-enyne 1a would increase the ratio of 3ah/4ah. However, the amount of 2h did not change the ratio of 3ah/4ah (Scheme 4). Therefore, the Scheme 4

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b01149. X-ray crystallographic information (CIF) Experimental procedures and compound characterization data (PDF)

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pathway via intermediate A is more plausible In our previous reports using acrylamides and enamides as alkenes, coordination of the carbonyl oxygen atom to rhodium suppresses the βhydride elimination to give the [2 + 2 + 2] cycloaddition products. In the reactions of aliphatic and aromatic alkenes, the β-hydride elimination proceeds due to the absence of the carbonyl oxygen atom. In the reactions shown in Scheme 2, the formation of the [2 + 2 + 2] cycloaddition products was not detected. The synthetic utility of the present cyclization product 3, derived from the aliphatic alkene 2c, is shown in Scheme 5. The enantioselective [2 + 2 + 2] cyclization of 1c with 2c followed by the hetero-Diels−Alder reaction with chloral14 in the presence of BF3·OEt2 at 0 °C afforded the corresponding spirocompounds 6 and 7 without racemization, although the diastereoselectivity was low. The synthetic utility of the present cyclization product 3, derived from the aromatic alkene 2k, is shown in Scheme 6.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Ken Tanaka: 0000-0003-0534-7559 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported partly by ACT-C (No. JPMJCR1122YR) from Japan Science and Technology Agency (Japan). K.M. thanks the JSPS Research Fellowship for Young Scientists (No. 15J07947). We thank Solvias AG for the gift of MeO-BIPHEP, Takasago Int. Corp. for the gift of Segphos and H8-BINAP, and Umicore for generous support in supplying the rhodium complex. 2915

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Organic Letters

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(14) (a) Benner, J. P.; Gill, G. B.; Parrott, S. J.; Wallace, B. J. Chem. Soc., Perkin Trans. 1 1984, 291. (b) Zhou, J.-H.; Cai, S.-H.; Xu, Y.-H.; Loh, T.-P. Org. Lett. 2016, 18, 2355. (15) (a) Sun, X.; Izumi, K.-J.; Hu, C.-Q.; Lin, G.-Q. Chin. J. Chem. 2006, 24, 430. (b) Jiang, H.; He, L.; Li, X.; Chen, H.; Wu, W.; Fu, W. Chem. Commun. 2013, 49, 9218. (c) Wu, J.; Yoshikai, N. Angew. Chem., Int. Ed. 2016, 55, 336. (d) Mao, M.; Zhang, L.; Chen, Y.-Z.; Zhu, J.; Wu, L. ACS Catal. 2017, 7, 181.

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DOI: 10.1021/acs.orglett.7b01149 Org. Lett. 2017, 19, 2913−2916