(R)-(+)-2,2-Dimethyl-1,3-dioxolane-4-carboxaldehyde

• CAS: 15186-48-8
• Catalog Number: ACM15186488
• Category: Main Products
• Molecular Weight: 130.14
• Molecular Formula: C₆H₁₀O₃
• Synonyms: (R)-2,2-DIMETHYL-[1,3]DIOXOLANE-4-CARBALDEHYDE;(R)-(+)-2,2-DIMETHYL-1,3-DIOXOLANE-4-CARBOXALDEHYDE;(R)-2,3-ISOPROPYLIDENE GLYCERALDEHYDE;1,3-DIOXOLANE-4-CARBOXALDEHYDE, 2,2-DIMETHYL-, (R)-;2,3-O-ISOPROPYLIDENE-D-GLYCERALDEHYDE;2,3-O-(R)-ISOPROPYLIDENE-L-GLYCERALDEHYDE;(4R)-2,2-DIMETHYL-1,3-DIOXOLANE-4-CARBALDEHYDE;D-(R)-GLYCERALDEHYDE ACETONIDE
• IUPAC Name: (4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde
• Canonical SMILES: CC1(OCC(O1)C=O)C
• InChI Key: YSGPYVWACGYQDJ-YFKPBYRVSA-N
• Boiling Point: 139°C(lit.)
• Flash Point: 143°F
• Density: 1.045g/mL at 25°C(lit.)
• Appearance: Oily liquid
• Exact Mass: 130.06300
• Supplemental Hazard Statements: H227-H303-H333-H351
• Symbol: GHS08
• WGK Germany: 3

Case Study

(R)-(+)-2,2-Dimethyl-1,3-Dioxolane-4-Carboxaldehyde for the Synthesis of Bicyclic Tetrahydrofuran Derivatives

Tiecco, Marcello, et al. Tetrahedron: Asymmetry, 2004, 15(12), 1949-1955.

From (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde, two bicyclic furan derived products, tetrahydrofuran[3,4-b]pyran and tetrahydrofuran[3,4-b]furan, can readily be prepared as pure enantiomers by extremely easy transformations and two electrophilic selenium-mediated cyclizations.
Synthesis procedure
· First, (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde was converted into olefinic protected diols 2 and 3. When n-BuLi (1.1 mmol) was added dropwise to white Ph3(PhCH2)P+Br- (1.1 mmol) solution in THF (10 mL) at 0 °C, the solution turned orange. This temperature was allowed to reach room temperature for 30 minutes and (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde was added for the reaction. Upon completion of the reaction, the mixture underwent extraction, the organic layer was dried, and chromatography followed by elution was conducted to acquire the desired diols.
· Subsequently, the diols were transformed into enantiomerically pure hydroxy-substituted tetrahydrofuran derivatives through cyclization with N-phenylselenophthalimide and BF3. The PhSe group at the C-4 position of these tetrahydrofurans was replaced with an allyl group using allyltributylstannane in the presence of AIBN. Selenium-mediated cyclizations of the allyl tetrahydrofurans, where the OH and allyl groups are arranged trans to each other, resulted in the formation of enantiopure perhydrofuro[3,4-b]pyrans, whereas cyclizations in which the OH and allyl groups are cis led to the production of perhydrofuro[3,4-b]furans. Finally, these bicyclic products were deselenenylated using triphenyltin hydride and AIBN.

(R)-(+)-2,2-Dimethyl-1,3-Dioxolane-4-Carboxaldehyde in Jiangrine C and D Total Synthesis

Zhang, Zhijiang, et al. Organic & Biomolecular Chemistry, 2017, 15(1), 207-212.

A silver-induced [3 + 2] cycloaddition reaction of terminal alkynes and isocyanides gave the total synthesis of jiangrine C and D, starting from (R)-(+)-2,2-Dimethyl-1,3-dioxolane-4-carboxaldehyde.
Synthesis steps
· It was started synthesising with (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde (8), which was treated with ethynyl magnesium bromide. This resulting alcohol was quickly oxidised to its methyl ether with sodium hydride and methyl iodide, and the two inseparable diastereomers 7a and 7b were combined in 1:1 amounts according to 1H NMR measurement.
· Then coupled together this diastereomeric mixture with ethyl 2-isocyanoacetate 6, using 10 mol% of silver carbonate to give compounds 5a and 5b in yields of 40%, and then they were separable by this point. The relative stereochemistry of compound 5a was established by X-ray crystallography.
· Compound 5 was then reacted with the known bromide 9 to make compound 4. Reduced lithium aluminum hydride and oxidized IBX in two steps to make 12. The target molecules (jiangrine C and D) were finally obtained in moderate yields using boron tribromide.

Synthetic Use

Upstream Synthesis Route 1

• 1707-77-3

• 15186-48-8

Reference: [1]Lorca, Miguel; Kuhn, Dan; Kurosu, Michio
[Tetrahedron Letters, 2001, vol. 42, # 36, p. 6243 - 6246]

Upstream Synthesis Route 2

• 52373-72-5

• 15186-48-8

Reference: [1]Jiang; Ma
[Synthetic Communications, 1995, vol. 25, # 22, p. 3641 - 3645]

Downstream Synthesis Route 1

• 15186-48-8

• 114746-70-2

Reference: [1] Tetrahedron, 1999, vol. 55, # 30, p. 9073 - 9088
[2] Tetrahedron Letters, 1985, vol. 26, # 50, p. 6193 - 6196

Downstream Synthesis Route 2

• 15186-48-8

• 23788-74-1

Reference: [1] Journal of Medicinal Chemistry, 1984, vol. 27, # 9, p. 1142 - 1149
[2] Chemical & Pharmaceutical Bulletin, 1981, vol. 29, # 12, p. 3593 - 3600

Downstream Synthesis Route 3

• 15186-48-8

• 83400-91-3

Reference: [1] Journal of Organic Chemistry USSR (English Translation), 1990, vol. 26, # 11, p. 2070 - 2081[2] Zhurnal Organicheskoi Khimii, 1990, vol. 26, # 11, p. 2398 - 2411

Downstream Synthesis Route 4

• 558-13-4
• 15186-48-8

• 56017-84-6

Reference: [1]Yadav, Ram N.; Paniagua, Armando; Banik, Bimal K.
[Journal of the Indian Chemical Society, 2021, vol. 98, # 4]

* For details of the synthesis route, please refer to the original source to ensure accuracy.