Nature Communications

Table 1 Optimization study

From: HFIP-assisted Brønsted acid-catalyzed ring opening of 1-azabicyclo[1.1.0]butane to access diverse C3-quaternary aza-azetidines and indole-azetidines


Entry	Solvent	Catalyst	Time	Temperature	Yield of 3a (%)
1	DCM	HCl	24 h	rt	0
2	DCM	H₃PO₄	24 h	rt	0
3	DCM	PhCO₂H	24 h	rt	0
4	DCM	TFA	24 h	rt	0
5	DCM	pTSA.H₂O	24 h	rt	0
6	DCM	ZnBr₂	24 h	rt	0
7	DCM	Cu(OTf)₂	24 h	rt	0
8	DCM	Zn(OTf)₂	24 h	rt	0
9	DCM	Sc(OTf)₃	24 h	rt	Trace
10	MeCN	pTSA.H₂O	24 h	rt	0
11	DMF	pTSA.H₂O	24 h	rt	Trace
12	DMSO	pTSA.H₂O	24 h	rt	trace
13	EtOH	pTSA.H₂O	24 h	rt	0
14	ⁱPrOH	pTSA.H₂O	24 h	rt	0
15	TFE	pTSA.H₂O	24 h	rt	15
16	HFIP	pTSA.H₂O	24 h	rt	85
17^b	HFIP	pTSA.H₂O	24 h	rt	78
18^c	HFIP	pTSA.H₂O	24 h	rt	75
19	HFIP	-	24 h	rt	20

^aReaction condition: 2a (0.2 mmol), indole (0.4 mmol), catalyst (10 mol%), HFIP (0.2 mL); after removal of HFIP add Et₃N (0.8 mmol), Boc₂O (0.4 mmol), DCM (5 mL).
^bpTSA.H₂O (5 mol%).
^cpTSA.H₂O (20 mol%).
^dAll yields are isolated yields after Boc-protection. For more optimization studies, see Supplementary Information, Table S1.

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