Synthesis of dihydropyrano[4,3-b]pyranes via a multi-component reaction catalyzed by lipase

Figures & data

Scheme 1. Synthesis of dihydropyrano[4,3-b]pyranes (4) catalyzed by lipase.

Table 1. Three-component reaction catalyzed by different lipases^a.

Entry	Catalysts	Yield (%)
1	PPL	89.2
2	PSL	65.9
3	CSL	83.4
4	BSL2	43.5
5	CAL-B	56.4
6	Denatured PPL^b	ND^c
7	None	ND^c

Note: Reaction condition: ^a 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol), i-propanol (5 mL), water content (15%), enzyme (120 U), 60 °C, 10 h; ^b PPL was denatured by heating it to 100 °C for 6 h in water before lyophilization; ^c ND: Not detected.

Table 2. Effect of organic solvents on the three-component reaction^a.

Solvent	Log P	Yield (%)
Cyclohexane	3.2	55.8
Toluene	2.7	42.1
Chloroform	1.61	48.7
Tetrahydrofuran	0.49	63.5
i-Propanol	−0.07	89.2
N,N-Dimethylformamide	−1.0	76.5
Ethanol	−0.24	83.4
Acetonitrile	−0.33	71.6

^aReaction condition: 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol), solvent (5 mL), water content (15%), PPL (120 U), 60 °C and 10 h.

Figure 1. Effect of temperature on the three-component reaction.

Notes: Reaction condition: 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol), i-propanol (5 mL), water content (15%), PPL (120 U), 10 h.

Figure 2. Effect of enzyme dosage on the three-component reaction.

Notes: Reaction condition: 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol), i-propanol (5 mL), water content (15%), 60°C, 10 h.

Figure 3. Effect of water content on the three-component reaction.

Notes: Reaction condition: 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol), i-propanol (5 mL), PPL (120 U), 60°C, 10 h.

Table 3. Synthesis of dihydropyrano[4,3-b]pyranes catalyzed by PPL with various aromatic aldehydes.

Entry	Aromatic aldehyde (1)	Yield (%)
1a		89.2
1b		81.3
1c		84.6
1d		85.5
1e		80.8
1f		83.4
1g		85.2
1h		90.5
1i		92.6
1j		90.3
1k		96.8
1l		94.7

Note: Reaction condition: 1a-1 l (1 mmol), 2 (1 mmol) and 3 (1 mmol), i-propanol (5 mL), water content (15%), PPL (120 U), 60°C and 10 h.