A combined experimental and computational study of NHC-catalyzed allylation of allenoate with MBH esters: new regiospecific and stereoselective access to 1,5-enyne

Abstract

An NHC-catalyzed regiospecific allylation of α-substituted allenoates with MBH carbonates derived from aryl aldehyde furnished highly functionalized 1,5-enynes bearing a quaternary carbon successfully. Combining with DFT calculations, the reaction mechanism of this conversion was proposed. This method has the advantages of high regioselectivity, good yields and mild reaction conditions. This transformation not only provided a new access to 1,5-enyne, but also enriched the chemistry of allenoates and NHC catalysis.

---

Introduction

1,5-Enynes are important and versatile synthetic intermediates with tunable transformations into a diverse array of cyclic skeletons.¹ So far, great achievements have been developed to assemble this valuable building block successfully, e.g., the allylation of propargylic electrophiles activated by either stoichiometric or catalytic amount of Lewis acids (Scheme 1a),² the Pd-catalyzed cross-coupling of chiral propargyl acetates with allyl boronates (Scheme 1b).³ However, the development of an organocatalyzed, efficient and facile protocol to construct this skeleton is still highly desirable due to its synthetic significance.

Scheme 1 Selective strategies to achieve functionalized 1,5-enynes.

Allenoates are reported as important synthetic materials to construct a wealth of valuable structurally complex molecules.⁴ So far, numerous allenoate-involved reactions catalyzed by phosphine or tertiary amine have been disclosed since Lu's pioneering work on phosphine-promoted [3 + 2] cycloaddition of allenoates with electron-deficient olefins in 1995.^5,6 Recently, N-heterocyclic carbenes (NHCs) have been widely employed to promote the conversions of aldehydes, carboxylic acids and carboxylic acids derivatives.⁷ As a type of Lewis bases, NHCs should also be able to facilitate those reactions catalyzed by phosphine or tertiary amine. Compared with the well-established phosphine or amine-catalyzed transformations of allenoates, in sharp contrast, the potential of the catalytic activity of NHC concerning the conversions of allenoates remains largely underexplored. The first study on the annulation variation was presented by Ye et al., where the imidazonium-based NHC was used to catalyze the [2 + 2 + 2] annulation of allenoate with two molecules of trifluoromethylketone, providing a six-membered cycloadduct.⁸

Subsequently, the Scheidt's group developed an NHC-catalyzed formal [2 + 2] annulation of γ-substituted allenoates with trifluoromethyl ketones for the diastereoselective assembly of oxetane.⁹ In terms of this, our group also reported a [4 + 2] annulation of chalcone with allenoate in the presence of imidazolium salt to build up a pyran scaffold with good chemoselectivity distinct from the previous works promoted by phosphine or tertiary amine (Scheme 2).¹⁰ In addition, NHC-catalyzed aldol-like condensations of allenoates with isatins have also been achieved by our lab recently.¹¹

Scheme 2 Reactions of allenoate with chalcone.

During the past decades, Morita–Baylis–Hillman (MBH) esters have evolved into important precursors for the syntheses of various complicated molecules and biologically active products.¹² Besides, they could also act as allylation reagents to introduce allyl group into the organic molecules.¹³ For instance, our team described a regiodivergent allylation of N-acylhydrazones with MBH ester recently.¹⁴ To continue our studies on the NHC-catalyzed transformations of allenoates and the exploration of new reaction patterns of MBH esters and allenoates, herein we performed an NHC-catalyzed reaction of MBH esters with allenoates, affording highly functionalized 1,5-enynes with regiospecifically and excellent stereoselectively (Scheme 1c).

Results and discussion

Our investigation commenced with the screening of NHC catalysts for the model reaction of 1a and 2a (Table 1), which showed that triazole-based catalysts could not catalyze the reaction. Thiazole salts could deliver trace products, and only imidazole catalysts pushed the reaction forward successfully (Table 1, entries 1–4). The adjustment of electronic nature of the catalyst through the replacement of t-butyl with aryl groups (catalyst B, C) led to the striking decrease of reaction yield. At the same time, we found that the steric hindrance of the catalyst substituent had a great influence on the reaction for the employment of catalyst D lowered the yield substantially. In addition, the installment of a methyl group on the backbone of catalyst had detrimental impact on the reaction. After several attempts, we found that catalyst A was able to furnish product 3a in 71% yield under ambient temperature in THF presented by Cs₂CO₃ (Table 1, entry 1). Subsequently, other Lewis bases including phosphine and tertiary amine were assessed, but no corresponding product was obtained (Table 1, entries 5–7). The investigation of solvents demonstrated that THF was superior to other counterparts. Further studies showed that THF was better than other ether-type solvents (Table 1, entries 8–16). Slight enhancement of the reaction temperature had no positive effect on the reaction yield (Table 1, entry 22). It should be worth mentioning that the unemployment of 4 Å MS led to a dramatic decrease in yield (Table 1, entry 23). Additionally, the increase of the amount of Cs₂CO₃ could not elevate the yield of product 3a (Table 1, entry 24). Thus, the optimal reaction conditions were identified eventually.

Table 1 Survey on reaction conditions for the formation of 3a^a

Entry	Catalyst	Base	Solvent	t (h)	Yield^b (%)	Z/E ratio^c
a Reactions were performed with 1a (0.12 mmol, 15.2 mg), 2a (0.10 mmol, 25.9 mg), catalyst (0.02 mmol), 4 Å MS (50 mg) and base (0.25 equiv.) in solvent (1.5 mL) under N2. b Overall yields based on 2a. c Determined by ^1H NMR assay. d Reaction was performed at 35 °C. e Reaction without 4 Å MS and was performed under air. f Cs2CO3 (0.5 equiv.). NR = no reaction. ND = not detected.
1	A	Cs2CO3	THF	12	71	>20 : 1
2	B	Cs2CO3	THF	24	NR
3	C–H	Cs2CO3	THF	24	Trace
4	I–M	Cs2CO3	THF	24	NR
5	Ph3P	—	THF	24	NR
6	DABCO	—	THF	24	NR
7	DMAP	—	THF	24	NR
8	A	Cs2CO3	Toluene	12	43	>20 : 1
9	A	Cs2CO3	DCM	12	40	>20 : 1
10	A	Cs2CO3	DCE	12	53	>20 : 1
11	A	Cs2CO3	ACN	12	66	>20 : 1
12	A	Cs2CO3	DMF	12	24	>20 : 1
13	A	Cs2CO3	MTBE	12	Trace
14	A	Cs2CO3	ETBE	12	Trace
15	A	Cs2CO3	Et2O	12	20	>20 : 1
16	A	Cs2CO3	2-MeTHF	12	34	>20 : 1
17	A	Na2CO3	THF	12	62	>20 : 1
18	A	K2CO3	THF	12	69	>20 : 1
19	A	^tBuOK	THF	12	57	>20 : 1
20	A	DMAP	THF	12	ND	ND
21	A	DABCO	THF	12	ND	ND
22^d	A	Cs2CO3	THF	12	67	>20 : 1
23^e	A	Cs2CO3	THF	24	10	>20 : 1
24^f	A	Cs2CO3	THF	12	56	>20 : 1

---

Having determined the optimal reaction conditions, the scope of variously substituted allenoates 1 and MBH esters 2 was investigated to delineate the influence of electronic and steric effects (Table 2). By placing a strong electron-donating group, such as CH₃O, at the para-position of phenyl of R³, substituted 1,5-enyne 3ab was furnished in low yield (Table 2, entry 2). Even if the reaction time was extended to 72 hours, the corresponding MBH carbonate could not be consumed completely. The incorporation of a relatively weak electron-donating methyl group at positions C2, C3 or C4 of the phenyl ring of R³ did not affect the efficiency of this reaction substantially (Table 2, entries 3–5). However, the methyl group at ortho position of the phenyl ring of R³ retarded the formation of cis-product (3ae, Z/E = 5 : 1), presumably due to the negative steric hindrance effect (Table 2, entry 5). Installation of electron-withdrawing groups at positions C2, C3 or C4 of the phenyl ring in the MBH carbonates 2 had not any obvious impact on the reactivity of allylation either (Table 2, entries 6–10). Limitedly, MBH carbonate (2k) derived from aliphatic aldehyde could not take part in this reaction system (Table 2, entry 18). Subsequently, the allenoates 1 scope was investigated. The α-benzyl allenoate was also proved to be suitable in such type of conversion (Table 2, entries 11, 12 and 17). Among these substrates, the allenoate (1c) possessing γ-phenyl provided the desired products in excellent yields (Table 2, entries 13–16). Allenoates having α,γ-dimethyl (1e) or γ-phenyl (1f) could also afford a moderate yield of expected product (Table 2, entries 18 and 19). These results highlighted the wide substrate scope, regiospecificity and high stereoselectivity of NHC-catalyzed allylation of allenoate with MBH esters.

Table 2 Exploration of substrate scope^a

Entry	R^1/R^2	R^3	3, yield^b (%)	t (h)	Z/E ratio^c
a Reactions were performed with 1a (0.12 mmol), 2a (0.10 mmol), A (0.02 mmol, 4.3 mg), and Cs2CO3 (0.025 mmol 8.1 mg) in THF (1.5 mL) under N2 at rt. b Isolated yields. c Z/E ratio determined by ^1H NMR assay. NR = no reaction, ND = not detected.
1	H/CH3(1a)	C6H5(2a)	3aa, 71	12	20/1
2	H/CH3(1a)	p-CH3OC6H4(2b)	3ab, 36	72	20/1
3	H/CH3(1a)	p-CH3C6H4(2c)	3ac, 74	12	20/1
4	H/CH3(1a)	m-CH3C6H4(2d)	3ad, 68	12	20/1
5	H/CH3(1a)	o-CH3C6H4(2e)	3ae, 71	12	5/1
6	H/CH3(1a)	p-ClC6H4(2f)	3af, 82	12	20/1
7	H/CH3(1a)	p-BrC6H4(2g)	3ag, 76	12	20/1
8	H/CH3(1a)	m-BrC6H4(2h)	3ah, 78	12	20/1
9	H/CH3(1a)	o-BrC6H4(2i)	3ai, 59	12	20/1
10	H/CH3(1a)	p-NO2C6H4(2j)	3aj, 72	12	20/1
11	H/Bn(1b)	C6H5(2a)	3ba, 66	12	20/1
12	H/Bn(1b)	p-ClC6H4(2f)	3bf, 84	12	20/1
13	Ph/CH3(1c)	C6H5(2a)	3ca, 91	12	20/1
14	Ph/CH3(1c)	p-CH3C6H4(2c)	3cc, 88	12	20/1
15	Ph/CH3(1c)	p-ClC6H4(2f)	3cf, 92	12	20/1
16	Ph/CH3(1c)	p-BrC6H4(2g)	3cg, 90	12	20/1
17	CH3/Bn(1d)	C6H5(2a)	3da, 83	12	20/1
18	CH3/CH3(1e)	C6H5(2a)	3ea, 49	12	20/1
19	Bn/CH3(1f)	C6H5(2a)	3fa, 47	12	20/1
20	Ph/CH3(1c)	C6H5CH2CH2(2k)	3ck, NR	24	ND

---

Finally, an unsubstituted allenoate (1g) was subject to this protocol and the reaction system became so complicated that we tried our best to obtain a purified product (3ga) in poor yield. Single-crystal X-ray diffraction showed that it was formed by the reaction of allenoate and MBH in the molar ratio of 1 : 2,¹⁵ and therefore the molar ratio of allenoate to MBH ester was set up to 1 : 2 to simplify the reaction system. However, the reaction delivered the mixture as before, providing product 3ga in moderate yield (Scheme 3).

Scheme 3 Reaction of Unsubstituted Allenoate with MBH Ester.^aa Reactions were performed with 1a (0.10 mmol), 2a (0.20 mmol), A (0.02 mmol, 4.3 mg), and Cs₂CO₃ (0.025 mmol 8.1 mg) in THF (1.5 mL) under N₂ at rt. ^b Isolated yields. ^c Z/E ratio determined by ¹H NMR assay.

Based on our observations, substrate 3a was employed to illustrate the reaction process, as shown in Fig. 1 and 2. DFT calculations were performed to shed some light on the reaction mechanism, which confirmed that the possible catalytic cycle contains five steps. All the structures have been optimized at the M06-2X¹⁶/6-31G(d,p) level in THF solvent using the in SMD mode¹⁷ in the Gaussian 09 program,¹⁸ and then the frequencies were computed at the same level to confirm the expected structures and provide the zero-point and thermal corrections. Higher basis set was employed to refine the single-point energy, which was used to plus the free energy corrections. More details and computed results have been provided in ESI.† In the first step, the carbene carbon of NHC attacks on the allene via transition state TS1 with an energy barrier of 18.7 kcal mol⁻¹. In the second step, the C–C bond formation occurs via transition state TS2 with an energy barrier of 13.5 kcal mol⁻¹. We have also considered and excluded the C–C bond formation pathway associated with the γ-carbon position via transition state TS2′ with an energy barrier of 15.0 kcal mol⁻¹. Subsequently, the OBoc⁻ group can be dissociated via transition state TS3. It should be noted that the energy barrier via transition state TS3 is 2.4 kcal mol⁻¹, but the energy difference between M2 and TS3 becomes negative (−0.5 kcal mol⁻¹), indicating the reaction step is a barrier-less process. In addition, we have also scrutinized and ruled out the dissociation pathway associated with the Z-isomer via transition state TS3′ with an energy barrier of 3.2 kcal mol⁻¹. In the fourth step, it is a deprotonation process via transition state TS4 with an energy barrier of 6.7 kcal mol⁻¹. The last step is the dissociation of the product 3 and NHC catalyst via transition state TS5 with an energy barrier of 14.3 kcal mol⁻¹.

Fig. 1 Our proposed reaction pathway.

Fig. 2 Relative Gibbs free-energy profile for NHC-catalyzed alkynylation by performing DFT calculate.

Conclusions

In summary, we have described a regiospecific allylation of α-substituted allenoate with MBH carbonate derived from aryl aldehyde, providing a facile access to the 1,5-enynes with multiple functional groups and a quaternary carbon in moderate to good yields with high E/Z selectivity. Further studies on the application of this protocol are underway in our lab.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

We are grateful for financial support by National Natural Science Foundation of China (No. 21871113, 21773214, 21372101), a project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institution and TAPP.

Notes and references

1. For selected works, see: (a) M. Nishida, N. Adachi, K. Onozuka, H. Matsumura and M. Mori, Intramolecular Cyclizations of Enynes Using RuClH(CO)(PPh₃)₃, J. Org. Chem., 1998, 63, 9158–9159; (b) O. Rhode and H. M. R. Hoffmann, Stereocontrolled Synthesis of Heteroannular Acetals from Functionalized 1,5-Enynes via Radical Cascades—Construction of Quaternary and 1,2-Diquaternary Centres in Polycyclic Systems, Tetrahedron, 2000, 56, 6479–6488; (c) M. R. Luzung, J. P. Markham and F. D. Toste, Catalaytic Isomerization of 1,5-Enynes to Bicyclo[3.1.0]hexenes, J. Am. Chem. Soc., 2004, 126, 10858–10859; (d) Y. Chen, D. M. Ho and C. Lee, Ruthenium-Catalyzed Hydrative Cyclization of 1,5-Enynes, J. Am. Chem. Soc., 2005, 127, 12184–12185; (e) J. Sun, M. P. Conley, L. Zhang and S. A. Kozmin, Au- and Pt-Catalyzed Cycloisomerizations of 1,5-Enynes to Cyclohexadienes with a Broad Alkyne Scope, J. Am. Chem. Soc., 2006, 128, 9705–9710; (f) S. Wang and L. Zhang, A Gold-Catalyzed Unique Cycloisomerization of 1,5-Enynes: Efficient Formation of 1-Carboxycyclohexa-1,4-dienes and Carboxyarenes, J. Am. Chem. Soc., 2006, 128, 14274–14275; (g) A. Buzas and F. Gagosz, Gold(I) Catalyzed Isomerization of 5-en-2-yn-1-yl Acetates: An Efficient Access to Acetoxy Bicyclo[3.1.0]hexenes and 2-Cycloalken-1-ones, J. Am. Chem. Soc., 2006, 128, 12614–12615; (h) O. Debleds and J.-M. Campagne, 1,5-Enyne Metathesis, J. Am. Chem. Soc., 2008, 130, 1562–1563; (i) K. Fukamizu, Y. Miyake and Y. Nishibayashi, Catalytic Cycloisomerization of 1,5-Enynes to 1,3-Cyclohexadienes via Ruthenium Vinylidene Intermediates, Angew. Chem., Int. Ed., 2009, 48, 2534–2537; (j) Y. Horino, T. Yamamoto, K. Ueda, S. Kuroda and F. D. Toste, Au(I)-Catalyzed Cycloisomerizations Terminated by sp³ C−H Bond Insertion, J. Am. Chem. Soc., 2009, 131, 2809–2811; (k) B. Crone, S. F. Kirsch and K.-D. Umland, Electrophilic Cyclization of 1,5-Enynes, Angew. Chem., Int. Ed., 2010, 49, 4661–4664; (l) D. Vasu, H.-H. Hung, S. Bhunia, S. A. Gawade, A. Das and R.-S. Liu, Gold-Catalyzed Oxidative Cyclization of 1,5-Enynes Using External Oxidants, Angew. Chem., Int. Ed., 2011, 50, 6911–6914; (m) C.-H. Chen, Y.-C. Tsai and R.-S. Liu, Gold-Catalyzed Cyclization/Oxidative [3 + 2] Cycloadditions of 1,5-Enynes with Nitrosobenzenes without Additional Oxidants, Angew. Chem., Int. Ed., 2013, 52, 4599–4603; (n) Z.-Z. Chen, S. Liu, W.-J. Hao, G. Xu, S. Wu, J.-N. Miao, B. Jiang, S.-L. Wang, S.-J. Tu and G. Li, Catalytic arylsulfonyl radical-triggered 1,5-enyne-bicyclizations and hydrosulfonylation of α,β-conjugates, Chem. Sci., 2015, 6, 6654–6658; (o) K. Speck, K. Karaghiosoff and T. Magauer, Sequential O–H/C–H Bond Insertion of Phenols Initiated by the Gold(I)-Catalyzed Cyclization of 1-Bromo-1,5-enynes, Org. Lett., 2015, 17, 1982–1985; (p) G.-Q. Chen, W. Fang, Y. Wei, X.-Y. Tang and M. Shi, Gold(I)-catalyzed dehydrogenative cycloisomerization of 1,5-enynes, Chem. Commun., 2016, 52, 10799–10802; (q) G.-Q. Chen, W. Fang, Y. Wei, X.-Y. Tang and M. Shi, Divergent reaction pathways in gold-catalyzed cycloisomerization of 1,5-enynes containing a cyclopropane ring: dramatic ortho substituent and temperature effects, Chem. Sci., 2016, 7, 4318–4328; (r) L.-Z. Yu, Y. Wei and M. Shi, Synthesis of Polysubstituted Polycyclic Aromatic Hydrocarbons by Gold-Catalyzed Cyclization–Oxidation of Alkylidenecyclopropane-Containing 1,5-Enynes, ACS Catal., 2017, 7, 4242–4247; (s) S. K. Scott, J. N. Sanders, K. E. White, R. A. Yu, K. N. Houk and A. J. Grenning, Controlling, Understanding, and Redirecting the Thermal Rearrangement of 3,3-Dicyano-1,5-enynes, J. Am. Chem. Soc., 2018, 140, 16134–16139; (t) J. Guo, X. Peng, X. Wang, F. Xie, X. Zhang, G. Liang, Z. Sun, Y. Liu, M. Cheng and Y. Liu, A gold-catalyzed cycloisomerization/aerobic oxidation cascade strategy for 2-aryl indenones from 1,5-enynes, Org. Biomol. Chem., 2018, 16, 9147–9151.
2. For selected works, see: (a) S. L. Schreiber, T. Sammakia and W. E. Crowe, A Lewis acid-mediated version of the Nicholas reaction: Synthesis of syn-alkylated products and cobalt-complexed cycloalkynes, J. Am. Chem. Soc., 1986, 108, 3128–3130; (b) M. Hayashi, A. Inubushi and T. Mukaiyama, A Convenient Method for the Preparation of Secondary Propargylic Ethers. The Reaction of Acetals with 1-Trimethylsilylalkynes Promoted by the Combined Use of Catalytic Amounts of Tin(IV) Chloride and Zinc Chloride, Chem. Lett., 1987, 16, 1975–1978; (c) J.-P. Dau-Schmidt and H. Mayr, Relative Reactivities of Alkyl Chlorides under Friedel-Crafts Conditions, Chem. Ber., 1994, 127, 205–212; (d) T. J. J. Müller and A. Netz, S_N1 reactions with planar chiral (arene)Cr(CO)₃-substituted α-propargyl cations - regio- and diastereoselective additions to novel ambident electrophiles, Tetrahedron Lett., 1999, 40, 3145–3148; (e) T. Ishikawa, M. Okano, T. Aikawa and S. Saito, Novel Carbon–Carbon Bond-Forming Reactions Using Carbocations Produced from Substituted Propargyl Silyl Ethers by the Action of TMSOTf, J. Org. Chem., 2001, 66, 4635–4642; (f) M. R. Luzung and F. D. Toste, Rhenium-Catalyzed Coupling of Propargyl Alcohols and Allyl Silanes, J. Am. Chem. Soc., 2003, 125, 15760–15761; (g) T. Schwier, M. Rubin and V. Gevorgyan, B(C₆F₅)₃-Catalyzed Allylation of Propargyl Acetates with Allylsilanes, Org. Lett., 2004, 6, 1999–2001; (h) Y. Kuninobu, E. Ishii and K. Takai, Rhenium- and Gold-Catalyzed Coupling of Aromatic Aldehydes with Trimethyl(phenylethynyl)silane: Synthesis of Diethynylmethanes, Angew. Chem., Int. Ed., 2007, 46, 3296–3299; (i) G. W. Kabalka, M.-L. Yao and S. Borella, Generation of Cations from Alkoxides: Allylation of Propargyl Alcohols, J. Am. Chem. Soc., 2006, 128, 11320–11321; (j) Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang, W.-Z. Yang and J.-P. Li, A General and Efficient FeCl₃-Catalyzed Nucleophilic Substitution of Propargylic Alcohols, J. Org. Chem., 2006, 71, 8298–8301; (k) R. Sanz, A. Martínez, D. Miguel, J. M. Álvarez-Gutiérrez and F. Rodríguez, Synthesis of 1,5-Enynes by Brønsted Acid Catalyzed Substitution of Propargylic Alcohols and One-Pot Synthesis of Bicyclo[3.1.0]hexenes, Synthesis, 2007, 3252–3256; (l) A. J. Lepore, D. M. Pinkerton and B. L. Ashfeld, Relay Redox and Lewis Acid Catalysis in the Titanocene- Catalyzed Multicomponent Assembly of 1,5-Enynes, Adv. Synth. Catal., 2013, 355, 1500–1504; (m) J. Mao, H. Li, H. Wen, M. Li, X. Fan and W. Bao, Palladium-Catalyzed Two-Component Domino Coupling Reaction of (Z)-β-Bromostyrenes with Norbornenes: Synthesis of 1,5-Enynes, Adv. Synth. Catal., 2016, 358, 1873–1879.
3. M. J. Ardolino and J. P. Morken, Construction of 1,5-Enynes by Stereospecific Pd-Catalyzed Allyl–Propargyl Cross-Couplings, J. Am. Chem. Soc., 2012, 134, 8770–8773.
4. For selected works, see: (a) S. Ma, Electrophilic Addition and Cyclization Reactions of Allenes, Acc. Chem. Res., 2009, 42, 1679–1688; (b) B. J. Cowen and S. J. Miller, Enantioselective catalysis and complexity generation from allenoates, Chem. Soc. Rev., 2009, 38, 3102–3116; (c) C.-K. Pei and M. Shi, Asymmetric Cyclization Reactions of Allenoates with Imines or α,β-Unsaturated Ketones Catalyzed by Organocatalysts Derived from Cinchona Alkaloids, Chem. – Eur. J., 2012, 18, 6712–6716; (d) S. Yu and S. Ma, Allenes in Catalytic Asymmetric Synthesis and Natural Product Syntheses, Angew. Chem., Int. Ed., 2012, 51, 3074–3112; (e) F. López and J. L. Mascareñas, [4 + 2] and [4 + 3] catalytic cycloadditions of allenes, Chem. Soc. Rev., 2014, 43, 2904–2915; (f) Z. Wang, X. Xu and O. Kwon, Phosphine catalysis of allenes with electrophiles, Chem. Soc. Rev., 2014, 43, 2927–2940; (g) T. Wang, X. Han, F. Zhong, W. Yao and Y. Lu, Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations, Acc. Chem. Res., 2016, 49, 1369–1378; (h) W. Zhou, H. Wang, M. Tao, C.-Z. Zhu, T.-Y. Lin and J. Zhang, Phosphine-catalyzed enantioselective [3 + 2] cycloadditions of γ-substituted allenoates with β-perfluoroalkyl enones, Chem. Sci., 2017, 8, 4660–4665.
5. C. Zhang and X. Lu, Phosphine-Catalyzed Cycloaddition of 2,3-Butadienoates or 2-Butynoates with Electron-Deficient Olefins. A Novel [3 + 2] Annulation Approach to Cyclopentenes, J. Org. Chem., 1995, 60, 2906–2908.
6. For reviews, see: (a) B. J. Cowen and S. J. Miller, Enantioselective catalysis and complexity generation from allenoates, Chem. Soc. Rev., 2009, 38, 3102–3116; (b) S. Ma, Electrophilic Addition and Cyclization Reactions of Allenes, Acc. Chem. Res., 2009, 42, 1679–1688; (c) H. Li and Y. Lu, Enantioselective Construction of All-Carbon Quaternary Stereogenic Centers by Using Phosphine Catalysis, Asian J. Org. Chem., 2017, 6, 1130–1145; (d) H. Guo, Y. C. Fan, Z. Sun, Y. Wu and O. Kwon, Phosphine Organocatalysis, Chem. Rev., 2018, 118, 10049–10293; (e) E.-Q. Li and Y. Huang, Recent advances in phosphine catalysis involving γ-substituted allenoates, Chem. Commun., 2020, 56, 680–694.
7. (a) D. M. Flanigan, F. Romanov-Michailidis, N. A. White and T. Rovis, Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes, Chem. Rev., 2015, 115, 9307–9387; (b) D. Enders, O. Niemeier and A. Henseler, Organocatalysis by N-Heterocyclic Carbenes, Chem. Rev., 2007, 107, 5606–5655; (c) X. Bugaut and F. Glorius, Organocatalytic umpolung: N-heterocyclic carbenes and beyond, Chem. Soc. Rev., 2012, 41, 3511–3522; (d) Y. Que, T. Li, C. Yu, X.-S. Wang and C. Yao, Enantioselective Assembly of Spirocyclic Oxindole-dihydropyranones through NHC-Catalyzed Cascade Reaction of Isatins with N-Hydroxybenzotriazole Esters of α,β-Unsaturated Carboxylic Acid, J. Org. Chem., 2015, 80, 3289–3294; (e) Y. Que, Y. Xie, T. Li, C. Yu, S. Tu and C. Yao, An N-Heterocyclic Carbene-Catalyzed Oxidative γ-Aminoalkylation of Saturated Carboxylic Acids through in Situ Activation Strategy: Access to δ-Lactam, Org. Lett., 2015, 17, 6234–6237; (f) Y. Wang, J. Pan, J. Dong, C. Yu, T. Li, X.-S. Wang, S. Shen and C. Yao, N-Heterocyclic Carbene-Catalyzed [4 + 2] Cyclization of Saturated Carboxylic Acid with o-Quinone Methides through in Situ Activation: Enantioselective Synthesis of Dihydrocoumarins, J. Org. Chem., 2017, 82, 1790–1795; (g) Y. Hu, D. Pan, L. Cong, Y. Yao, C. Yu, T. Li and C. Yao, NHC-Catalyzed Efficient Syntheses of Isoquinolinones or Isochromanones through Formal [4 + 2] Cycloaddition of o-Quinodimethanes with Acylhydrazones or Ketones, ChemistrySelect, 2018, 3, 1708–1712.
8. L. Sun, T. Wang and S. Ye, N-Heterocyclic Carbene-Catalyzed [2 + 2 + 2] Annulation of Allenoates with Trifluoromethylketones, Chin. J. Chem., 2012, 30, 190–194.
9. S. S. Lopez, A. A. Jaworski and K. A. Scheidt, NHC-Catalyzed Formal [2 + 2] Annulations of Allenoates for the Synthesis of Substituted Oxetanes, J. Org. Chem., 2018, 83, 14637–14645.
10. (a) A. Voituriez, A. Panossian, N. Fleury-Brégeot, P. Retailleau and A. Marinetti, 2-Phospha[3]ferrocenophanes with Planar Chirality: Synthesis and Use in Enantioselective Organocatalytic [3 + 2] Cyclizations, J. Am. Chem. Soc., 2008, 130, 14030–14031; (b) K. D. Ashtekar, R. J. Staples and B. Borhan, Development of a Formal Catalytic Asymmetric [4 + 2] Addition of Ethyl-2,3-butadienoate with Acyclic Enones, Org. Lett., 2011, 13, 5732–5735; (c) Y. Hu, S. Li, Z. Wang, Y. Yao, T. Li, C. Yu and C. Yao, NHC-Catalyzed Hetero-Diels–Alder Reaction of Allenoate with Chalcone: Synthesis of Polysubstituted Pyranyl Carboxylate, J. Org. Chem., 2018, 83, 3361–3366.
11. S. Li, Z. Tang, Y. Wang, D. Wang, Z. Wang, C. Yu, T. Li, D. Wei and C. Yao, NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates, Org. Lett., 2019, 21, 1306–1310.
12. For reviews, see: (a) V. Singh and S. Batra, Advances in the Baylis–Hillman reaction-assisted synthesis of cyclic frameworks, Tetrahedron, 2008, 64, 4511–4574; (b) G.-N. Ma, J.-J. Jiang, M. Shi and Y. Wei, Recent extensions of the Morita–Baylis–Hillman reaction, Chem. Commun., 2009, 5496–5514; (c) D. Basavaiah, B. S. Reddy and S. S. Badsara, Recent Contributions from the Baylis−Hillman Reaction to Organic Chemistry, Chem. Rev., 2010, 110, 5447–5674; (d) T.-Y. Liu, M. Xie and Y.-C. Chen, Organocatalytic asymmetric transformations of modified Morita–Baylis–Hillman adducts, Chem. Soc. Rev., 2012, 41, 4101–4112; (e) N.-J. Zhong, Y.-Z. Wang, L. Cheng, D. Wang and L. Liu, Recent advances in the annulation of Morita–Baylis–Hillman adducts, Org. Biomol. Chem., 2018, 16, 5214–5227.
13. (a) C.-W. Cho, J.-R. Kong and M. J. Krische, Phosphine-Catalyzed Regiospecific Allylic Amination and Dynamic Kinetic Resolution of Morita–Baylis–Hillman Acetates, Org. Lett., 2004, 6, 1337–1339; (b) J. Liu, Z. Han, X. Wang, F. Meng, Z. Wang and K. Ding, Palladium-Catalyzed Asymmetric Construction of Vicinal Tertiary and All-Carbon Quaternary Stereocenters by Allylation of β-Ketocarbonyls with Morita–Baylis–Hillman Adducts, Angew. Chem., Int. Ed., 2017, 56, 5050–5054; (c) Q.-Q. Zhao, J. Chen, D.-M. Yan, J.-R. Chen and W.-J. Xiao, Photocatalytic Hydrazonyl Radical-Mediated Radical Cyclization/Allylation Cascade: Synthesis of Dihydropyrazoles and Tetrahydropyridazines, Org. Lett., 2017, 19, 3620–3623; (d) J. Qi, J. Zheng and S. Cui, Fe(III)-Catalyzed Hydroallylation of Unactivated Alkenes with Morita–Baylis–Hillman Adducts, Org. Lett., 2018, 20, 1355–1358; (e) G.-Y. Chen, F. Zhong and Y. Lu, Highly Enantioselective and Regioselective Substitution of Morita–Baylis–Hillman Carbonates with Nitroalkanes, Org. Lett., 2011, 13, 6070–6073.
14. F. Sun, T. Yin, A. Feng, Y. Hu, C. Yu, T. Li and C. Yao, Base-promoted regiodivergent allylation of N-acylhydrazones with Morita–Baylis–Hillman carbonates by tuning the catalyst, Org. Biomol. Chem., 2019, 17, 5283–5293.
15. Crystallographic data (excluding structure factors) for the structures (3ga) in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 2117224.†.
16. (a) Y. Zhao and D. G. Truhlar, Exploring the Limit of Accuracy of the Global Hybrid Meta Density Functional for Main-Group Thermochemistry, Kinetics, and Noncovalent Interactions, J. Chem. Theory Comput., 2008, 4, 1849–1868; (b) Y. Zhao and D. G. Truhlar, Density Functionals with Broad Applicability in Chemistry, Acc. Chem. Res., 2008, 41, 157–167.
17. A. V. Marenich, C. J. Cramer and D. G. Truhlar, Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions, J. Phys. Chem. B, 2009, 113, 6378–6396.
18. G. W. Trucks, M. J. Frisch, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Revision C.01, 2010.

---

Footnotes

† Electronic supplementary information (ESI) available. CCDC 2117224. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1qo01083b

‡ These authors contributed equally to this work.

---