Asymmetric Synthesis of AB Rings in ent-Kaurene Carbon Framework

doi:10.6023/cjoc202108029

Abstract

The total synthesis of ent-kaurene natural products of Xerophilusin I, Neolaxiflorin L, Eriocalyxin B, 15-epi- Enmelol completed by diversity-oriented synthesis strategy. In this paper, the regioselectivity of Horner-Wadsworth-Emmons reaction was optimized, and a single Z configuration was transformed from Z/E mixture under acidic condition. Based on the conversion of a single configuration under mild acidic conditions, a mechanism for hydrogen bond-assisted Michael addition/retro-Michael elimination is proposed. The asymmetric Diels-Alder reaction with silylenol ether dienyl 3 and β-ketoate 1 as dienophile was developed. Using Cu(OTf)₂ as Lewis acid and oxazoline as chiral ligand, AB-ring-skeleton was constructed with 65% yield and >19∶1 dr value.

Key words: ent-kaurane, Horner-Wadsworth-Emmons reaction, regioselectivity, asymmetric Diels-Alder reaction

Cite this article

Wenjing Ma, Lizhi Zhu, Mengxun Zhang, Chising Lee. Asymmetric Synthesis of AB Rings in ent-Kaurene Carbon Framework[J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 580-589.

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References 10

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Entry	Additive (equiv.)	Temp./℃	t/h	Z∶E
1	TEA (10.0)	r.t.	72	1∶2.5
2	2,6-Lutidine (10.0)	r.t.	72	1∶2.5
3	DABCO (10.0)	r.t.	72	1∶2.5
4	2,6-Lutidine (10.0)	Reflux	72	1∶10
5	1 mol/L HCl/THF (2.5)	r.t.	3	Single E

Entry	Additive (equiv.)	Temp./℃	t/h	Z∶E
1	TEA (10.0)	r.t.	72	1∶2.5
2	2,6-Lutidine (10.0)	r.t.	72	1∶2.5
3	DABCO (10.0)	r.t.	72	1∶2.5
4	2,6-Lutidine (10.0)	Reflux	72	1∶10
5	1 mol/L HCl/THF (2.5)	r.t.	3	Single E

Ligand	Yield^a/%	Recovery/% of 3	(+)-14a∶(–)-14b	exo/endo
L₁	33	40	1∶1.5	>10∶1
L₂	30	52	1∶3	>10∶1
L₃	67	31	2.5∶1	>10∶1
L₄	No reaction	70	—	—
L₅	32	50	1∶1	6∶1
L₆	65	27	5∶1	>10∶1
L₇	63	28	1∶ 2	8∶1
L₈	33	45	1.5∶1	>10∶1

Ligand	Yield^a/%	Recovery/% of 3	(+)-14a∶(–)-14b	exo/endo
L₁	33	40	1∶1.5	>10∶1
L₂	30	52	1∶3	>10∶1
L₃	67	31	2.5∶1	>10∶1
L₄	No reaction	70	—	—
L₅	32	50	1∶1	6∶1
L₆	65	27	5∶1	>10∶1
L₇	63	28	1∶ 2	8∶1
L₈	33	45	1.5∶1	>10∶1

Entry	Solvent	Temp./℃	n(Lewis acid)∶n(ligand)	Cu(OTf)₂/mol%	Yield^a/% of (+)-14a	dr^b
1	Dichloromethane (DCM)	r.t.	1∶1.1	10	65	5∶1
2	1,2-Dichloroethane (DCE)	r.t.	1∶1.1	10	63	8∶1
3	Chlorobenzene	r.t.	1∶1.1	10	42	2.5∶1
4	1,2-Dichlorobenzene	r.t.	1∶1.1	10	48	3.5∶1
5	1,1,1-Trichloroethane	r.t.	1∶1.1	10	58	2.5∶1
6	Trichloromethane	r.t.	1∶1.1	10	43	3∶1
7	1,3-Dichloropropane	r.t.	1∶1.1	10	53	6∶1
8	DCE/toluene (V∶V=1∶1)	r.t.	1∶1.1	10	48	2.5∶1
9	DCE/toluene (V∶V=3∶1)	r.t.	1∶1.1	10	54	5∶1
10	DCE	r.t.	1∶1.5	10	65	13∶1
11	DCE	r.t.	1∶1.1	5	65	13∶1
12	DCE	r.t.	1∶1.1	1	—	—
13	DCE	0	1∶1.1	10	65	15∶1
14	DCE	0	1∶1.5	5	65	>19∶1

ent-Kaurene全碳骨架中AB环系的不对称合成